52 results on '"Romina Salpini"'
Search Results
2. New insights into hepatitis B virus lymphotropism: Implications for HBV-related lymphomagenesis
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Valentina Svicher, Romina Salpini, Stefano D’Anna, Lorenzo Piermatteo, Marco Iannetta, Vincenzo Malagnino, and Loredana Sarmati
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Cancer Research ,Oncology - Abstract
HBV is one of the most widespread hepatitis viruses worldwide, and a correlation between chronic infection and liver cancer has been clearly reported. The carcinogenic capacity of HBV has been reported for other solid tumors, but the largest number of studies focus on its possible lymphomagenic role. To update the correlation between HBV infection and the occurrence of lymphatic or hematologic malignancies, the most recent evidence from epidemiological and in vitro studies has been reported. In the context of hematological malignancies, the strongest epidemiological correlations are with the emergence of lymphomas, in particular non-Hodgkin’s lymphoma (NHL) (HR 2.10 [95% CI 1.34-3.31], p=0.001) and, more specifically, all NHL B subtypes (HR 2.14 [95% CI 1.61-2.07], pin vitro studies have shown the ability of HBV to infect, albeit not productively, both lymphomonocytes and bone marrow stem cells, whose differentiation is halted by the virus. As demonstrated in animal models, HBV infection of blood cells and the persistence of HBV DNA in peripheral lymphomonocytes and bone marrow stem cells suggests that these cellular compartments may act as HBV reservoirs, allowing replication to resume later in the immunocompromised patients (such as liver transplant recipients) or in subjects discontinuing effective antiviral therapy. The pathogenetic mechanisms at the basis of HBV carcinogenic potential are not known, and more in-depth studies are needed, considering that a clear correlation between chronic HBV infection and hematological malignancies could benefit both antiviral drugs and vaccines.
- Published
- 2023
3. Targeting SARS-CoV-2 nsp13 Helicase and Assessment of Druggability Pockets: Identification of Two Potent Inhibitors by a Multi-Site In Silico Drug Repurposing Approach
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Isabella Romeo, Francesca Alessandra Ambrosio, Giosuè Costa, Angela Corona, Mohammad Alkhatib, Romina Salpini, Saverio Lemme, Davide Vergni, Valentina Svicher, Maria Mercedes Santoro, Enzo Tramontano, Francesca Ceccherini-Silberstein, Anna Artese, and Stefano Alcaro
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drug repurposing ,SARS-CoV-2 ,Organic Chemistry ,Drug Repositioning ,DNA Helicases ,Pharmaceutical Science ,COVID-19 ,Viral Nonstructural Proteins ,Antiviral Agents ,Analytical Chemistry ,Settore MED/07 ,COVID-19 Drug Treatment ,helicase ,Chemistry (miscellaneous) ,SARS-CoV-2 (COVID-19) ,nsp13 ,conservation analysis ,inhibitory activity ,Drug Discovery ,Molecular Medicine ,Humans ,Physical and Theoretical Chemistry ,RNA Helicases - Abstract
The SARS-CoV-2 non-structural protein 13 (nsp13) helicase is an essential enzyme for viral replication and has been identified as an attractive target for the development of new antiviral drugs. In detail, the helicase catalyzes the unwinding of double-stranded DNA or RNA in a 5′ to 3′ direction and acts in concert with the replication–transcription complex (nsp7/nsp8/nsp12). In this work, bioinformatics and computational tools allowed us to perform a detailed conservation analysis of the SARS-CoV-2 helicase genome and to further predict the druggable enzyme’s binding pockets. Thus, a structure-based virtual screening was used to identify valuable compounds that are capable of recognizing multiple nsp13 pockets. Starting from a database of around 4000 drugs already approved by the Food and Drug Administration (FDA), we chose 14 shared compounds capable of recognizing three out of four sites. Finally, by means of visual inspection analysis and based on their commercial availability, five promising compounds were submitted to in vitro assays. Among them, PF-03715455 was able to block both the unwinding and NTPase activities of nsp13 in a micromolar range.
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- 2022
4. Novel concepts on mechanisms underlying Hepatitis Delta virus persistence and related pathogenesis
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Romina Salpini, Stefano D'Anna, Lorenzo Piermatteo, and Valentina Svicher
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Hepatitis B virus ,Hepatitis B Surface Antigens ,Hepatology ,Liver Neoplasms ,Virus Replication ,Settore MED/07 ,Infectious Diseases ,HDV variability ,Virology ,Hepatitis Delta ,Humans ,HDV pathogenesis ,Hepatitis Delta Virus ,HDV persistence - Abstract
Hepatitis Delta virus is the smallest known human virus, exploiting the HBV surface proteins (HBsAg) for the release of its progeny and de novo entry into hepatocytes. Ever growing evidence have highlighted the existence of multiple mechanisms underlying HDV persistence including integrated HBV-DNA as a source of HBsAg production and the capability of the HDV genome to propagate through cell proliferation, thus supporting a potential HDV persistence even in the absence of HBV. Chronic HDV-infection causes the most severe form of viral hepatitis, leading to the development of cirrhosis in 15% of cases within 1-2 years and in 50%-60% of cases within 5-10 years. The rates of hepatocellular carcinoma and hepatic decompensation are also 2-3-fold higher than for HBV mono-infection. There is the evidence that persistent viral replication plays a key role in triggering liver injury, suggesting the existence of direct viral cytopathic properties that can modulate, synergistically with immune-responses, the progression towards end-stage liver diseases. All these aspects can be further exacerbated by the extraordinary degree of viral genetic variability that can promote HDV evasion from immune responses and has enabled viral differentiation into genotypes and subgenotypes with potential different pathobiological properties. In this light, this review aims at providing comprehensive insights of mechanisms (with a focus on virological factors) underlying HDV persistence and pathogenesis, critical in shaping the clinical outcome of the infection. Dissecting these mechanisms is pivotal to optimize therapeutic strategies aimed at fully counteracting this fascinating and fearsome virus.
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- 2022
5. SARS-CoV-2 Mutations and Variants May Muddle the Sensitivity of COVID-19 Diagnostic Assays
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Mohammad Alkhatib, Luca Carioti, Stefano D’Anna, Francesca Ceccherini-Silberstein, Valentina Svicher, and Romina Salpini
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Microbiology (medical) ,diagnostic-escape ,variants ,PCR ,primer-mismatches ,SARS-CoV-2 ,Virology ,COVID-19 ,mutations ,Microbiology ,Settore MED/07 - Abstract
The performance of diagnostic polymerase chain reaction (PCR) assays can be impacted by SARS-CoV-2 variability as this is dependent on the full complementarity between PCR primers/probes and viral target templates. Here, we investigate the genetic variability of SARS-CoV-2 regions recognized by primers/probes utilized by PCR diagnostic assays based on nucleotide mismatching analysis. We evaluated the genetic variation in the binding regions of 73 primers/probes targeting the Nucleocapsid (N, N = 36), Spike (S, N = 22), and RNA-dependent RNA-polymerase/Helicase (RdRp/Hel, N = 15) of the publicly available PCR-based assays. Over 4.9 million high-quality SARS-CoV-2 genome sequences were retrieved from GISAID and were divided into group-A (all except Omicron, >4.2 million) and group-B (only Omicron, >558 thousand). In group-A sequences, a large range of variability in primers/probes binding regions in most PCR assays was observed. Particularly, 87.7% (64/73) of primers/probes displayed ≥1 mismatch with their viral targets, while 8.2% (6/73) contained ≥2 mismatches and 2.7% (2/73) contained ≥3 mismatches. In group-B sequences, 32.9% (24/73) of primers/probes were characterized by ≥1 mismatch, 13.7% (10/73) by ≥2 mismatches, and 5.5% (4/73) by ≥3 mismatches. The high rate of single and multiple mismatches- found in the target regions of molecular assays used worldwide for SARS-CoV-2 diagnosis reinforces the need to optimize and constantly update these assays according to SARS-CoV-2 genetic evolution and the future emergence of novel variants.
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- 2022
6. Update on SARS-CoV-2 Omicron Variant of Concern and Its Peculiar Mutational Profile
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Mohammad Alkhatib, Romina Salpini, Luca Carioti, Francesca Alessandra Ambrosio, Stefano D’Anna, Leonardo Duca, Giosuè Costa, Maria Concetta Bellocchi, Lorenzo Piermatteo, Anna Artese, Maria Mercedes Santoro, Stefano Alcaro, Valentina Svicher, and Francesca Ceccherini-Silberstein
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Microbiology (medical) ,Vaccines ,General Immunology and Microbiology ,Ecology ,Physiology ,SARS-CoV-2 ,pandemic ,B.1.1.519 ,COVID-19 ,emerging variants ,Cell Biology ,mutations ,omicron ,Spike Glycoprotein ,Settore MED/07 ,Coronavirus ,Infectious Diseases ,Mutation ,Spike Glycoprotein, Coronavirus ,Genetics ,Humans ,variant of concern - Abstract
The process of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genetic diversification is still ongoing and has very recently led to the emergence of a new variant of concern (VOC), defined as Omicron or B.1.1.529. Omicron VOC is the most divergent variant identified so far and has generated immediate concern for its potential capability to increase SARS-CoV-2 transmissibility and, more worryingly, to escape therapeutic and vaccine-induced antibodies. Nevertheless, a clear definition of the Omicron VOC mutational spectrum is still missing. Herein, we provide a comprehensive definition and functional characterization (in terms of infectivity and/or antigenicity) of mutations characterizing the Omicron VOC. In particular, 887,475 SARS-CoV-2 Omicron VOC whole-genome sequences were retrieved from the GISAID database and used to precisely define its specific patterns of mutations across the different viral proteins. In addition, the functional characterization of Omicron VOC spike mutations was finely discussed according to published manuscripts. Lastly, residues characterizing the Omicron VOC and the previous four VOCs (Alpha, Beta, Gamma, and Delta) were mapped on the three-dimensional structure of the SARS-CoV-2 spike protein to assess their localization in the different spike domains. Overall, our study will assist with deciphering the Omicron VOC mutational profile and will shed more light on its clinical implications. This is critical considering that Omicron VOC is currently the predominant variant worldwide.
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- 2022
7. Identification of gp120 polymorphisms in HIV-1 B subtype potentially associated with resistance to fostemsavir
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Valentina Svicher, Maria Mercedes Santoro, Romina Salpini, Francesca Ceccherini-Silberstein, L. Carioti, Stefano Aquaro, Yagai Bouba, Carlo Federico Perno, Giulia Berno, and Lavinia Fabeni
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0301 basic medicine ,Microbiology (medical) ,Lymphocyte ,T cell ,030106 microbiology ,HIV Infections ,HIV Envelope Protein gp120 ,Biology ,medicine.disease_cause ,Major histocompatibility complex ,Piperazines ,Epitope ,Settore MED/07 ,03 medical and health sciences ,Immune system ,Polymorphism (computer science) ,Drug Resistance, Viral ,medicine ,Humans ,Pharmacology (medical) ,Pharmacology ,Mutation ,Virology ,Organophosphates ,030104 developmental biology ,Infectious Diseases ,medicine.anatomical_structure ,HIV-1 ,biology.protein ,Antibody - Abstract
Objectives We evaluated natural resistance to the new antiretroviral fostemsavir and its potential association with other HIV-1 gp120 polymorphisms. Methods A total of 1997 HIV-1 B subtype gp120 sequences from the Los Alamos HIV Database were analysed for mutation prevalence at fostemsavir resistance-associated positions and potential association with other gp120 polymorphisms. The role of each fostemsavir resistance-related position and the correlated gp120 mutations, both in protein stability and in reducing the binding affinity between antibody and/or T cell lymphocyte epitopes and the MHC molecules, was estimated. Results The prevalence of fostemsavir resistance mutations was as follows: L116Q (0.05%), S375H/M/T (0.55%/1.35%/17.73%, the latter being far less relevant in determining resistance), M426L (7.56%), M434I (4.21%) and M475I (1.65%). Additionally, the M426R polymorphism had a prevalence of 16.32%. A significantly higher prevalence in X4 viruses versus R5 viruses was found only for S375M (0.69% versus 3.93%, P = 0.009) and S375T (16.60% versus 22.11%, P = 0.030). Some fostemsavirv resistance positions positively and significantly correlated with specific gp120 polymorphisms: S375T with I371V; S375M with L134W, I154V and I323T; M475I with K322A; and M426R with G167N, K192T and S195N. The topology of the dendrogram suggested the existence of three distinct clusters (bootstrap ≥0.98) involving these fostemsavir resistance mutations and gp120 polymorphisms. Interestingly, all clustered mutations are localized in class I/II-restricted T cell/antibody epitopes, suggesting a potential role in immune HIV escape. Conclusions A low prevalence of known fostemsavir resistance mutations was found in the HIV-1 B subtype. The detection of novel HIV-1 gp120 polymorphisms potentially relevant for fostemsavir resistance deserves new in-depth in vitro investigations.
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- 2020
8. HBeAg Levels Vary across the Different Stages of HBV Infection According to the Extent of Immunological Pressure and Are Associated with Therapeutic Outcome in the Setting of Immunosuppression-Driven HBV Reactivation
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Carla Fontana, Patrick T F Kennedy, Elisa Basile, Carlotta Cerva, Valentina Svicher, Maria De Cristofaro, A. Iuvara, L. Piermatteo, Stefano D’Anna, Francesca Ceccherini-Silberstein, Mariantonietta Pisaturo, Loredana Sarmati, Carmine Minichini, Mohammad Alkhatib, Mario Starace, Romina Salpini, Eleonora Andreassi, Sandro Grelli, Massimo Andreoni, Upkar S. Gill, Ada Bertoli, Vincenzo Malagnino, Nicola Coppola, Giuseppina Cappiello, Piermatteo, Lorenzo, Alkhatib, Mohammad, D'Anna, Stefano, Malagnino, Vincenzo, Bertoli, Ada, Andreassi, Eleonora, Basile, Elisa, Iuvara, Alessandra, De Cristofaro, Maria, Cappiello, Giuseppina, Cerva, Carlotta, Minichini, Carmine, Pisaturo, Mariantonietta, Starace, Mario, Coppola, Nicola, Fontana, Carla, Grelli, Sandro, Ceccherini-Silberstein, Francesca, Andreoni, Massimo, Gill, Upkar S, Kennedy, Patrick T F, Sarmati, Loredana, Salpini, Romina, Svicher, Valentina, Piermatteo, L., Alkhatib, M., D'Anna, S., Malagnino, V., Bertoli, A., Andreassi, E., Basile, E., Iuvara, A., De Cristofaro, M., Cappiello, G., Cerva, C., Minichini, C., Pisaturo, M., Starace, M., Coppola, N., Fontana, C., Grelli, S., Ceccherini-Silberstein, F., Andreoni, M., Gill, U. S., Kennedy, P. T. F., Sarmati, L., Salpini, R., and Svicher, V.
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Treatment response ,medicine.medical_specialty ,HBsAg ,QH301-705.5 ,medicine.medical_treatment ,viruses ,Hbv reactivation ,HBV reactivation ,Medicine (miscellaneous) ,HBeAg ,Gastroenterology ,General Biochemistry, Genetics and Molecular Biology ,Article ,Internal medicine ,medicine ,HBV ,Biology (General) ,Natural course ,business.industry ,virus diseases ,Immunosuppression ,cccDNA ,Settore MED/17 ,digestive system diseases ,Chronic infection ,business - Abstract
HBeAg is a marker of HBV-activity, and HBeAg-loss predicts a favorable clinical outcome. Here, we characterize HBeAg-levels across different phases of HBV infection, their correlation with virological/biochemical markers and the virological response to anti-HBV therapy. Quantitative HBeAg (qHBeAg, DiaSorin) is assessed in 101 HBeAg+ patients: 20 with acute-infection, 20 with chronic infection, 32 with chronic hepatitis and 29 with immunosuppression-driven HBV-reactivation (HBV-R). A total of 15/29 patients with HBV-R are monitored for >, 12 months after starting TDF/ETV. qHBeAg is higher in immunosuppression-driven HBV-R (median[IQR]:930[206–1945]PEIU/mL) and declines in chronic hepatitis (481[28–1393]PEIU/mL, p = 0.03), suggesting HBeAg production, modulated by the extent of immunological pressure. This is reinforced by the negative correlation between qHBeAg and ALT in acute infection (Rho = −0.66, p = 0.006) and chronic hepatitis (Rho = −0.35, p = 0.05). Interestingly, qHBeAg strongly and positively correlates with qHBsAg across the study groups, suggesting cccDNA as a major source of both proteins in the setting of HBeAg positivity (with limited contribution of integrated HBV-DNA to HBsAg production). Focusing on 15 patients with HBV-R starting TDF/ETV, virological suppression and HBeAg-loss are achieved in 60% and 53.3%. Notably, the combination of qHBeAg >, 2000 PEIU/mL + qHBsAg >, 52,000 IU/mL at HBV-R is the only factor predicting no HBeAg loss (HBeAg loss: 0% with vs. 72.7% without qHBeAg >, 52,000 IU/mL, p = 0.03). In conclusion, qHBeAg varies over the natural course of HBV infection, according to the extent of immunological pressure. In the setting of HBV-R, qHBeAg could be useful in predicting the treatment response under immunosuppression.
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- 2021
9. Serum HBsAg and ddPCR HBV-DNA as predictive parameters of HBsAg loss after nucleo (s)tide analogue (NA) treatment discontinuation in non-cirrhotic patients with chronic hepatitis B
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Anna Francesca Guerra, Giovanni Tomassoli, Lorenzo Piermatteo, Stefano D’Anna, Romina Salpini, Valentina Svicher, Paolo Ventura, Gian Luca Abbati, and Antonello Pietrangelo
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Hepatology - Published
- 2022
10. Establishment of a Seronegative Occult Infection With an Active Hepatitis B Virus Reservoir Enriched of Vaccine Escape Mutations in a Vaccinated Infant After Liver Transplantation
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Maria Concetta Bellocchi, Paola Francalanci, Rossana Scutari, L. Piermatteo, L. Carioti, Marco Ciotti, Romina Salpini, Maria Sole Basso, Mohammed Alkhatib, Marianna Aragri, Daniela Liccardo, Valentina Svicher, Manila Candusso, and Andrea Pietrobattista
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0301 basic medicine ,Hepatitis B virus ,medicine.medical_treatment ,Liver transplantation ,Virus Replication ,medicine.disease_cause ,Polymerase Chain Reaction ,Virus ,hepatitis B occult infection ,Settore MED/07 ,law.invention ,HBV reservoir ,digital droplet PCR ,liver transplantation ,vaccine escape mutations ,03 medical and health sciences ,0302 clinical medicine ,Antigen ,law ,medicine ,Humans ,Immunology and Allergy ,Polymerase chain reaction ,biology ,Transmission (medicine) ,business.industry ,Vaccination ,Hepatitis B ,Virology ,030104 developmental biology ,Infectious Diseases ,Liver ,Child, Preschool ,DNA, Viral ,Mutation ,biology.protein ,Female ,030211 gastroenterology & hepatology ,Antibody ,business ,Biomarkers - Abstract
We describe the establishment of a seronegative occult hepatitis B virus (HBV) infection (OBI) in a successfully vaccinated infant who underwent liver transplantation from an donor positive for antibody to hepatitis B core antigen (anti-HBc). The use of highly sensitive droplet digital polymerase chain reaction assays revealed a not negligible and transcriptionally active intrahepatic HBV reservoir (circular covalently closed DNA, relaxed circular DNA, and pregenomic RNA: 5.6, 2.4, and 1.1 copies/1000 cells, respectively), capable to sustain ongoing viral production and initial liver damage. Next-generation sequencing revealed a peculiar enrichment of hepatitis B surface antigen vaccine-escape mutations that could have played a crucial role in OBI transmission. This clinical case highlights the pathobiological complexity and the diagnostic challenges underlying OBI.
- Published
- 2019
11. Current status of antivirals and druggable targets of SARS CoV-2 and other human pathogenic coronaviruses
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Valentina Svicher, Romina Salpini, Francesca Alessandra Ambrosio, Maria Mercedes Santoro, Anna Artese, Giosuè Costa, Yehuda G. Assaraf, Velia Chiara Di Maio, Francesca Ceccherini-Silberstein, Stefano Alcaro, and Mohammad Alkhatib
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0301 basic medicine ,Cancer Research ,Secondary ,viruses ,Druggability ,Spike ,Drug resistance ,medicine.disease_cause ,Protein Structure, Secondary ,Settore MED/07 ,0302 clinical medicine ,Drug Delivery Systems ,Coronaviridae ,Pharmacology (medical) ,Coronavirus ,biology ,Antiviral resistance ,Drug repositioning ,Infectious Diseases ,Oncology ,RNA polymerase ,030220 oncology & carcinogenesis ,Nucleoside analogs ,Reverse Transcriptase Inhibitors ,Coronavirus Infections ,Protein Structure ,Conservation ,Antiviral Agents ,Virus ,Article ,03 medical and health sciences ,medicine ,Animals ,Humans ,Protease Inhibitors ,Amino Acid Sequence ,Pharmacology ,SARS-CoV-2 ,Outbreaks ,COVID-19 ,biology.organism_classification ,Virology ,Protease ,Protein Structure, Tertiary ,COVID-19 Drug Treatment ,030104 developmental biology ,Viral replication ,Entry inhibitors ,DrugBank ,Tertiary - Abstract
Coronaviridae is a peculiar viral family, with a very large RNA genome and characteristic appearance, endowed with remarkable tendency to transfer from animals to humans. Since the beginning of the 21st century, three highly transmissible and pathogenic coronaviruses have crossed the species barrier and caused deadly pneumonia, inflicting severe outbreaks and causing human health emergencies of inconceivable magnitude. Indeed, in the past two decades, two human coronaviruses emerged causing serious respiratory illness: severe acute respiratory syndrome coronavirus (SARS-CoV-1) and Middle Eastern respiratory syndrome coronavirus (MERS-CoV), causing more than 10,000 cumulative cases, with mortality rates of 10 % for SARS-CoV-1 and 34.4 % for MERS-CoV. More recently, the severe acute respiratory syndrome coronavirus virus 2 (SARS-CoV-2) has emerged in China and has been identified as the etiological agent of the recent COVID-19 pandemic outbreak. It has rapidly spread throughout the world, causing nearly 22 million cases and ∼ 770,000 deaths worldwide, with an estimated mortality rate of ∼3.6 %, hence posing serious challenges for adequate and effective prevention and treatment. Currently, with the exception of the nucleotide analogue prodrug remdesivir, and despite several efforts, there is no known specific, proven, pharmacological treatment capable of efficiently and rapidly inducing viral containment and clearance of SARS-CoV-2 infection as well as no broad-spectrum drug for other human pathogenic coronaviruses. Another confounding factor is the paucity of molecular information regarding the tendency of coronaviruses to acquire drug resistance, a gap that should be filled in order to optimize the efficacy of antiviral drugs. In this light, the present review provides a systematic update on the current knowledge of the marked global efforts towards the development of antiviral strategies aimed at coping with the infection sustained by SARS-CoV-2 and other human pathogenic coronaviruses, displaying drug resistance profiles. The attention has been focused on antiviral drugs mainly targeting viral protease, RNA polymerase and spike glycoprotein, that have been tested in vitro and/or in clinical trials as well as on promising compounds proven to be active against coronaviruses by an in silico drug repurposing approach. In this respect, novel insights on compounds, identified by structure-based virtual screening on the DrugBank database endowed by multi-targeting profile, are also reported. We specifically identified 14 promising compounds characterized by a good in silico binding affinity towards, at least, two of the four studied targets (viral and host proteins). Among which, ceftolozane and NADH showed the best multi-targeting profile, thus potentially reducing the emergence of resistant virus strains. We also focused on potentially novel pharmacological targets for the development of compounds with anti-pan coronavirus activity. Through the analysis of a large set of viral genomic sequences, the current review provides a comprehensive and specific map of conserved regions across human coronavirus proteins which are essential for virus replication and thus with no or very limited tendency to mutate. Hence, these represent key druggable targets for novel compounds against this virus family. In this respect, the identification of highly effective and innovative pharmacological strategies is of paramount importance for the treatment and/or prophylaxis of the current pandemic but potentially also for future and unavoidable outbreaks of human pathogenic coronaviruses.
- Published
- 2020
12. Key mutations in the C-terminus of the HBV surface glycoprotein correlate with lower HBsAg levels
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Romina, Salpini, Arianna, Battisti, Lorenzo, Piermatteo, Luca, Carioti, Olympia E, Anastasiou, Upkar S, Gill, Domenico, Di Carlo, Luna, Colagrossi, Leonardo, Duca, Ada, Bertoli, Katia Yu, La Rosa, Lavinia, Fabeni, Alessandra, Iuvara, Vincenzo, Malagnino, Carlotta, Cerva, Miriam, Lichtner, Claudio M, Mastroianni, Giuseppe Maria, De Sanctis, Maurizio, Paoloni, Massimo, Marignani, Caterina, Pasquazzi, Nerio, Iapadre, Giustino, Parruti, Jacopo, Vecchiet, Loredana, Sarmati, Massimo, Andreoni, Mario, Angelico, Sandro, Grelli, Patrick, T Kennedy, Jens, Verheyen, Stefano, Aquaro, Francesca Ceccherini, Silberstein, Carlo Federico, Perno, and Valentina, Svicher
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Adult ,Male ,Hepatitis B virus ,Hepatitis B Surface Antigens ,Genotype ,virus diseases ,HBeAg-negative infection ,Middle Aged ,digestive system diseases ,Article ,Hepatitis B, Chronic ,HBV genotypes ,Mutation ,HBsAg levels ,HBsAg mutations ,Humans ,HBsAg C-terminus ,Female - Abstract
Increasing evidences suggest that HBsAg-production varies across HBV-genotypes. HBsAg C-terminus plays a crucial role for HBsAg-secretion. Here, we evaluate HBsAg-levels in different HBV-genotypes in HBeAg-negative chronic infection, the correlation of specific mutations in HBsAg C-terminus with HBsAg-levels in-vivo, their impact on HBsAg-secretion in-vitro and on structural stability in-silico. HBsAg-levels were investigated in 323 drug-naïve HBeAg-negative patients chronically infected with HBV genotype-D(N = 228), -A(N = 65) and -E(N = 30). Genotype-D was characterized by HBsAg-levels lower than genotype-A and -E (3.3[2.7–3.8]IU/ml; 3.8[3.5–4.2]IU/ml and 3.9[3.7–4.2]IU/ml, P
- Published
- 2020
13. Quantification of intrahepatic total HBV DNA in liver biopsies of HBV-infected patients by a modified version of COBAS® Ampliprep/COBAS®TaqMan HBV test v2.0
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S. Giannella, Tania Guenci, Valentina Serafini, Marco Ciotti, Patrick T F Kennedy, A. Battisti, Valentina Svicher, Upkar S. Gill, Francesca Stazi, L. Piermatteo, Carlo Federico Perno, and Romina Salpini
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Adult ,Male ,Microbiology (medical) ,Hepatitis B virus ,Serial dilution ,Biopsy ,Immunology ,Biology ,HBV DNA level ,medicine.disease_cause ,Virus ,v2.0 ,Settore MED/07 ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Plasmid ,medicine ,Humans ,Immunology and Allergy ,COBAS® TaqMan HBV test, v2.0 ,HBV reservoir ,Intrahepatic HBV DNA ,DNA, Viral ,Female ,Hepatitis B, Chronic ,Liver ,Reproducibility of Results ,Viral Load ,Viral ,Chronic ,medicine.diagnostic_test ,virus diseases ,DNA ,General Medicine ,Hepatitis B ,medicine.disease ,Virology ,digestive system diseases ,COBAS® TaqMan HBV test ,chemistry ,030220 oncology & carcinogenesis ,030211 gastroenterology & hepatology ,Viral load - Abstract
Intrahepatic total HBV DNA (it-HBV DNA) level might reflect the size of virus reservoir and correlate with the histological status of the liver. To quantitate it-HBV DNA in a series of 70 liver biopsies obtained from hepatitis B chronic patients, a modified version of the COBAS®Ampliprep/COBAS®TaqMan HBV test v2.0 was used for this purpose. The linearity and reproducibility of the modified protocol was tested by quantifying serial dilutions of a full-length HBV containing plasmid and it-HBV DNA from a reference patient. A good linear trend between the expected values and those generated by the assay was observed at different concentrations of both plasmid and reference patient (R 2 = 0.994 and 0.962, respectively). Differences between the values obtained in two independent runs were ≤0.3 log IU for the plasmid and ≤0.6 log IU/mg for the reference patient, showing a high inter-run reproducibility. In the 70 liver biopsies, it-HBV DNA level ranged from 1.4 to 5.4 log IU/mg, with a good linearity and reproducibility between the values obtained in two runs [R 2 = 0.981; median (IQR) difference of it-HBV DNA 0.05 (0.02-0.09) IU/mg]. The modified COBAS®Ampliprep/COBAS®TaqMan HBV test v2.0 allows an accurate quantitation of it-HBV DNA. Its determination may have prognostic value and may be a useful tool for the new therapeutic strategies aimed at eradicating the HBV infection.
- Published
- 2017
14. Different Patterns of HIV-1 Replication in MACROPHAGES is Led by Co-Receptor Usage
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Maria Vittoria Mauro, Alessandro Ranazzi, Francesca Ceccherini-Silberstein, Valentina Svicher, Ana Borrajo, Stefano Aquaro, Carlo Federico Perno, Maria Concetta Bellocchi, Michela Pollicita, and Romina Salpini
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0301 basic medicine ,Medicine (General) ,Programmed cell death ,Benzylamines ,Receptors, CXCR4 ,Co-receptor ,genetic structures ,Receptors, CCR5 ,Anti-HIV Agents ,viruses ,Cell ,DNA Fragmentation ,Cyclams ,CXCR4 ,Article ,Settore MED/07 ,03 medical and health sciences ,Chemokine receptor ,R5-920 ,human immunodeficiency virus ,monocyte-derived macrophages ,α chemokine receptor 4 ,β-chemokine receptor 5 ,HIV-1 ,Heterocyclic Compounds ,Humans ,Macrophages ,0302 clinical medicine ,Receptors ,Medicine ,Receptor ,business.industry ,Microarray analysis techniques ,virus diseases ,General Medicine ,Cell biology ,030104 developmental biology ,medicine.anatomical_structure ,Apoptosis ,030220 oncology & carcinogenesis ,business ,CCR5 - Abstract
Background and objectives: To enter the target cell, HIV-1 binds not only CD4 but also a co-receptor &beta, chemokine receptor 5 (CCR5) or &alpha, chemokine receptor 4 (CXCR4). Limited information is available on the impact of co-receptor usage on HIV-1 replication in monocyte-derived macrophages (MDM) and on the homeostasis of this important cellular reservoir. Materials and Methods: Replication (measured by p24 production) of the CCR5-tropic 81A strain increased up to 10 days post-infection and then reached a plateau. Conversely, the replication of the CXCR4-tropic NL4.3 strain (after an initial increase up to day 7) underwent a drastic decrease becoming almost undetectable after 10 days post-infection. The ability of CCR5-tropic and CXCR4-tropic strains to induce cell death in MDM was then evaluated. While for CCR5-tropic 81A the rate of apoptosis in MDM was comparable to uninfected MDM, the infection of CXCR4-tropic NL4.3 in MDM was associated with a rate of 14.3% of apoptotic cells at day 6 reaching a peak of 43.5% at day 10 post-infection. Results: This suggests that the decrease in CXCR4-tropic strain replication in MDM can be due to their ability to induce cell death in MDM. The increase in apoptosis was paralleled with a 2-fold increase in the phosphorylated form of p38 compared to WT. Furthermore, microarray analysis showed modulation of proapoptotic and cancer-related genes induced by CXCR4-tropic strains starting from 24 h after infection, whereas CCR5 viruses modulated the expression of genes not correlated with apoptotic-pathways. Conclusions: In conclusion, CXCR4-tropic strains can induce a remarkable depletion of MDM. Conversely, MDM can represent an important cellular reservoir for CCR5-tropic strains supporting the role of CCR5-usage in HIV-1 pathogenesis and as a pharmacological target to contribute to an HIV-1 cure.
- Published
- 2019
15. Characterisation of HIV-1 molecular transmission clusters among newly diagnosed individuals infected with non-B subtypes in Italy
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L. Carioti, Annalisa Mondi, Roberta Gagliardini, Miriam Lichtner, Ada Bertoli, Ombretta Turriziani, Alessandra Vergori, Francesca Ceccherini-Silberstein, Rossana Scutari, Manuela Colafigli, Federica Forbici, Andrea Antinori, Carmela Pinnetti, Nicoletta Orchi, Massimo Andreoni, Cristina Mussini, Caterina Gori, Claudia Alteri, Lavinia Fabeni, Enrico Girardi, Vanni Borghi, Gabriella De Carli, Francesco Montella, Maria Mercedes Santoro, Romina Salpini, Alfredo Pennica, Giulia Berno, Carlo Federico Perno, Laura Mazzuti, and Stefania Cicalini
- Subjects
0301 basic medicine ,Oncology ,Adult ,Male ,medicine.medical_specialty ,Settore MED/17 - Malattie Infettive ,Genotype ,030106 microbiology ,HIV ,molecular epidemiology ,transmission dynamics ,transmission networks ,virology HIV ,Human immunodeficiency virus (HIV) ,Prevalence ,HIV Infections ,Dermatology ,Newly diagnosed ,medicine.disease_cause ,Logistic regression ,Settore MED/07 ,Men who have sex with men ,03 medical and health sciences ,Internal medicine ,Epidemiology ,medicine ,Disease Transmission, Infectious ,Cluster Analysis ,Humans ,Phylogeny ,Molecular Epidemiology ,Molecular epidemiology ,business.industry ,Transmission (medicine) ,Middle Aged ,030104 developmental biology ,Infectious Diseases ,Italy ,HIV-1 ,Female ,business - Abstract
ObjectiveWe evaluated the characteristics of HIV-1 molecular transmission clusters (MTCs) in 1890 newly diagnosed individuals infected with non-B subtypes between 2005 and 2017 in Italy.MethodsPhylogenetic analyses were performed on pol sequences to characterise subtypes/circulating recombinant forms and identify MTCs. MTCs were divided into small (SMTCs, 2–3 sequences), medium (MMTCs, 4–9 sequences) and large (LMTCs, ≥10 sequences). Factors associated with MTCs were evaluated using logistic regression analysis.Results145 MTCs were identified and involved 666 individuals (35.2%); 319 of them (16.9%) were included in 13 LMTCs, 111 (5.9%) in 20 MMTCs and 236 (12.5%) in 112 SMTCs. Compared with individuals out of MTCs, individuals involved in MTCs were prevalently Italian (72.7% vs 30.9%, p9/L: 0.4 (0.265–0.587) vs 0.246 (0.082–0.417), p10 copies/mL: 4.8 (4.2–5.5) vs 5.0 (4.3–5.5), p=0.87). Logistic regression confirmed that certain factors such as being MSM, of Italian origin, younger age and higher CD4 cell count were significantly associated with MTCs.ConclusionsOur findings show that HIV-1 newly diagnosed individuals infected with non-B subtypes are involved in several MTCs in Italy. These MTCs include mainly Italians and MSM and highlight the complex phenomenon characterising the HIV-1 spread. This is important especially in view of monitoring the HIV epidemic and guiding the public health response.
- Published
- 2019
16. Combined Analysis of the Prevalence of Drug-Resistant Hepatitis B Virus in Antiviral Therapy-Experienced Patients in Europe (CAPRE)
- Author
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Rolf Kaiser, Snjezana Zidovec Lepej, G. J. Boland, Henrik Krarup, Lucas Etienne Hermans, Carole Seguin-Devaux, Dimitrios Paraskevis, Simona Paraschiv, Nijaz Tihic, Ivana Lazarevic, François Simon, Maja M. Lunar, Romina Salpini, Sarah Maylin, Pascale Trimoulet, Nicola Coppola, Adriana Vince, Mario Poljak, Nina Weis, Bianca Bruzzone, Tülay Yalcinkaya, Tomasz Dyda, Suzan D. Pas, Valeria Micheli, Maja Stanojevic, Annemarie M. J. Wensing, Valentina Svicher, Carlo Federico Perno, Orna Mor, Marta Álvarez, Federico García, Jens Verheyen, Charles A. Boucher, Sukran Kose, Kathrine Stene-Johansen, Ziv Ben Ari, Elisabeth Puchhammer-Stöckl, Virology, Hermans, Lucas Etienne, Svicher, Valentina, Pas, Suzan Diepstraten, Salpini, Romina, Alvarez, Marta, Ben Ari, Ziv, Boland, Greet, Bruzzone, Bianca, Coppola, Nicola, Seguin Devaux, Carole, Dyda, Tomasz, Garcia, Federico, Kaiser, Rolf, Köse, Sukran, Krarup, Henrik, Lazarevic, Ivana, Lunar, Maja M, Maylin, Sarah, Micheli, Valeria, Mor, Orna, Paraschiv, Simona, Paraskevis, Dimitrio, Poljak, Mario, Puchhammer Stöckl, Elisabeth, Simon, Françoi, Stanojevic, Maja, Stene Johansen, Kathrine, Tihic, Nijaz, Trimoulet, Pascale, Verheyen, Jen, Vince, Adriana, Weis, Nina, Yalcinkaya, Tülay, Lepej, Snjezana Zidovec, Perno, Carlo, Boucher, Charles A. B, and Wensing, Annemarie M. J.
- Subjects
0301 basic medicine ,Male ,Cross-sectional study ,hepatitis B viru ,Medizin ,Drug Resistance ,Drug resistance ,medicine.disease_cause ,Gastroenterology ,0302 clinical medicine ,Genotype ,Prevalence ,Immunology and Allergy ,Viral ,Chronic ,Non-U.S. Gov't ,Research Support, Non-U.S. Gov't ,antiviral drug resistance ,Lamivudine ,Entecavir ,Middle Aged ,Hepatitis B ,Settore MED/07 - Microbiologia e Microbiologia Clinica ,3. Good health ,Multicenter Study ,Infectious Diseases ,nucleos(t)ide analogs ,030211 gastroenterology & hepatology ,Female ,Viral load ,medicine.drug ,Adult ,medicine.medical_specialty ,Hepatitis B virus ,030106 microbiology ,Research Support ,Antiviral Agents ,Virus ,03 medical and health sciences ,Hepatitis B, Chronic ,SDG 3 - Good Health and Well-being ,Internal medicine ,Drug Resistance, Viral ,medicine ,Journal Article ,Humans ,genotypic resistance testing ,business.industry ,Virology ,hepatitis B virus ,Cross-Sectional Studies ,business - Abstract
INTRODUCTION: European guidelines recommend treatment of chronic Hepatitis B virus infection (CHB) with the nucleos(t)ide analogs (NAs) entecavir or tenofovir. However, many European CHB patients have been exposed to other NAs, which are associated with therapy failure and resistance. The CAPRE study was performed to gain insight in prevalence and characteristics of NA resistance in Europe.METHODS: A survey was performed on genotypic resistance testing results acquired during routine monitoring of CHB patients with detectable serum HBV-DNA in European tertiary referral centres.RESULTS: Data of 1568 patients was included. The majority (73.8%) was exposed to lamivudine monotherapy. Drug resistant strains were detected in 52.7%. The most frequently encountered primary mutation was M204V/I (48.7%), followed by A181T/V (3.8%) and N236T (2.6%). In patients exposed to entecavir (n=102), full resistance was present in 35.3%. Independent risk factors for resistance were age, viral load and lamivudine exposure (pCONCLUSION: These findings support resistance testing in cases of apparent NA therapy failure. This survey highlights the impact of exposure to lamivudine and adefovir on development of drug resistance and cross-resistance. Continued use of these NAs needs to be reconsidered at a pan-European level.
- Published
- 2016
17. The integrated use of accurate virological and serological HBV markers can help identifying HBsAg-negative/anti-HBC-positive patients at higher risk of HBV-reactivation and optimizing the duration of prophylaxis in oncohematological setting
- Author
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Romina Salpini, Carlotta Cerva, Mohammad Alkhatib, Lorenzo Piermatteo, Arianna Battisti, Vincenzo Malagnino, Lavinia Fabeni, Maria Cantonetti, William Arcese, Francesca Ceccherini Silberstein, Carlo Federico Perno, Massimo Andreoni, Loredana Sarmati, and Valentina Svicher
- Subjects
Hepatology - Published
- 2020
18. Quantitative HBeAg varies in the different phases of HBV infection, and can predict therapeutic outcome in the setting of immunosuppression driven HBV reactivation
- Author
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Lorenzo Piermatteo, Romina Salpini, Mohammad Alkhatib, Ada Bertoli, Alessandra Iuvara, Maria De Cristofaro, Giuseppina Cappiello, Carlotta Cerva, Carmine Minichini, Mario Starace, Mariantonietta Pisaturo, Nicola Coppola, Carla Fontana, Loredana Sarmati, Massimo Andreoni, Angelico Mario, Sandro Grelli, Francesca Ceccherini Silberstein, Carlo Federico Perno, and Valentina Svicher
- Subjects
Hepatology - Published
- 2020
19. Cryptic HBV viremia in anti-HBC positive/HBsAg negative patients with HIV infection is frequently revealed by applying an ultrasensitive droplet digital PCR assay
- Author
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Romina Salpini, Vincenzo Malagnino, Mohammad Alkhatib, Lorenzo Piermatteo, Rossana Scutari, Riccardo Chirichiello, Tizana Mulas, Ada Bertoli, Katia Yu La Rosa, Marta Brugneti, Marco Ciotti, Massimo Andreoni, Carlo Federico Perno, Francesca Ceccherini Silberstein, Loredana Sarmati, and Valentina Svicher
- Subjects
Hepatology - Published
- 2020
20. The novel HBx mutation F30V correlates with hepatocellular carcinoma in vivo, reduces hepatitis B virus replicative efficiency and enhances anti-apoptotic activity of HBx N terminus in vitro
- Author
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Francesca Ceccherini-Silberstein, Rossana Scutari, Massimo Andreoni, Mario Angelico, Carmen Mirabelli, Massimo Levrero, Laura Belloni, Maria Francesca Cortese, Loredana Sarmati, Gabriele Missale, Caterina Pasquazzi, Valentina Svicher, J. Vecchiet, Simona Francioso, G.A. Palumbo, Matteo Surdo, A. Sacco, Hervé Fleury, Pascale Trimoulet, Carlo Federico Perno, L. Carioti, Mohammad Alkhatib, Alberto Spanò, Giuseppina Cappiello, and Romina Salpini
- Subjects
0301 basic medicine ,Microbiology (medical) ,Adult ,Male ,apoptosis ,hbx ,hepatitis b ,hepatitis b virus replication ,hepatocellular carcinoma ,Hepatitis B virus ,Carcinoma, Hepatocellular ,Genotype ,030106 microbiology ,Apoptosis ,Biology ,medicine.disease_cause ,Virus Replication ,03 medical and health sciences ,0302 clinical medicine ,Hepatitis B, Chronic ,medicine ,Humans ,Viral Regulatory and Accessory Proteins ,030212 general & internal medicine ,Aged ,Mutation ,Liver Neoplasms ,General Medicine ,cccDNA ,Hep G2 Cells ,Hepatitis B ,Middle Aged ,Settore MED/07 - Microbiologia e Microbiologia Clinica ,medicine.disease ,digestive system diseases ,HBx ,Infectious Diseases ,Liver ,Structural Homology, Protein ,Hepatocellular carcinoma ,DNA, Viral ,Cancer research ,Trans-Activators ,Female - Abstract
We aimed to investigate HBx genetic elements correlated with hepatitis B virus (HBV) -related hepatocellular carcinoma (HCC) and their impact on (a) HBV replicative efficiency, (b) HBx binding to circular covalently closed DNA (cccDNA), (c) apoptosis and cell-cycle progression, and (d) HBx structural stability.This study included 123 individuals chronically infected with HBV: 27 with HCC (77.9% (21/27) genotype D; 22.1% (6/27) genotype A) and 96 without HCC (75% (72/96) genotype D; 25.0% (24/96) genotype A). HepG2 cells were transfected by wild-type or mutated linear HBV genome to assess pre-genomic RNA (pgRNA) and core-associated HBV-DNA levels, HBx-binding onto cccDNA by chromatin immunoprecipitation-based quantitative assay, and rate of apoptosis and cell-cycle progression by cytofluorimetry.F30V was the only HBx mutation correlated with HCC (18.5% (5/27) in HCC patients versus 1.0% (1/96) in non-HCC patients, p 0.002); a result confirmed by multivariate analysis. In vitro, F30V determined a 40% and 60% reduction in pgRNA and core-associated HBV-DNA compared with wild-type (p0.05), in parallel with a significant decrease of HBx binding to cccDNA and decreased HBx stability. F30V also decreased the percentage of apoptotic cells compared with wild-type (14.8 ± 6.8% versus 19.1 ± 10.1%, p0.01, without affecting cell-cycle progression) and increased the probability of HBx-Ser-31 being phosphorylated by PI3K-Akt kinase (known to promote anti-apoptotic activity).F30V was closely correlated with HBV-induced HCC in vivo, reduced HBV replicative efficiency by affecting HBx-binding to cccDNA and increased anti-apoptotic HBx activity in vitro. This suggests that F30V (although hampering HBV's replicative capacity) may promote hepatocyte survival, so potentially allowing persistent production of viral progeny and initiating HBV-driven hepatocarcinogenesis. Investigation of viral genetic markers associated with HCC is crucial to identify those patients at higher risk of HCC, who hence deserve intensive liver monitoring and/or early anti-HBV therapy.
- Published
- 2018
21. SAT-190-Specific genetic elements in HBsAg C-terminus profoundly affect HBsAg levels in vivo, hamper HBsAg secretion in vitro and alter HBsAg structural stability in HBeAg-negative chronic HBV genotype D infection
- Author
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Patrick T F Kennedy, Ada Bertoli, Carlo Federico Perno, Massimo Marignani, Jens Verheyen, Paoloni Maurizio, L. Carioti, T. Mari, Vincenzo Malagnino, Carlotta Cerva, L. Colagrossi, Angelico Mario, Giustino Parruti, Jacopo Vecchiet, A. Battisti, Francesca Ceccherini Silberstein, A. Iuvara, Olympia E. Anastasiou, Upkar S. Gill, Claudio Maria Mastroianni, Miriam Lichtner, L. Piermatteo, Giuseppe Maria De Sanctis, Caterina Pasquazzi, Romina Salpini, Sandro Grelli, Massimo Andreoni, N. Iapadre, Loredana Sarmati, Marianna Aragri, and Valentina Svicher
- Subjects
HBsAg ,Hepatology ,Hbeag negative ,In vivo ,C-terminus ,Hbv genotype ,Secretion ,Biology ,Affect (psychology) ,Virology ,In vitro - Published
- 2019
22. SAT-159-Genetic determinants in critical domains of NS5A are associated with genotype 1b HCV-induced hepatocellular carcinoma
- Author
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Rossana Scutari, Valeria Cento, C. Masetti, Elisabetta Teti, Francesca Ceccherini Silberstein, Cristina Mussini, Massimo Andreoni, Ada Bertoli, Simona Francioso, Caterina Pasquazzi, Marianna Aragri, Silvia Barbaliscia, Carlo Federico Perno, Vincenza Calvaruso, Ivana Maida, Giustino Parruti, Valentina De Murtas, Angelica Sacco, Velia Chiara Di Maio, Mohammad Alkhatib, Ilaria Lenci, Federica Sozio, Angelico Mario, Alessandro Pieri, Maria Mercedes Santoro, Vanni Borghi, Antonio Craxì, Filomena Morisco, Valeria Pace Palitti, Romina Salpini, Valentina Svicher, Sergio Babudieri, Ennio Polilli, and P. Cacciatore
- Subjects
Hepatology ,Genotype 1b ,Hepatocellular carcinoma ,medicine ,Cancer research ,Biology ,NS5A ,medicine.disease - Published
- 2019
23. GS-17-The integration of Hepatitis B virus into human genome is a common event in the setting of HBeAg negative disease: Implications for the treatment and management of CHB
- Author
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Romina Salpini, Patrick T F Kennedy, Matteo Surdo, A. Battisti, Andrea Nuccitelli, L. Piermatteo, Carlo Federico Perno, N. Hansi, Valeria Cacciafesta, L. Colagrossi, Francesca Ceccherini Silberstein, Upkar S. Gill, and Valentina Svicher
- Subjects
Hepatitis B virus ,Hepatology ,Hbeag negative ,business.industry ,Event (relativity) ,medicine ,Human genome ,Disease ,medicine.disease_cause ,business ,Virology - Published
- 2019
24. Hepatitis B reactivation characterized by HBsAg negativity and anti-HbsAg antibodies persistence in haematopoietic stem cell transplanted patient after lamivudine withdrawal
- Author
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L. Colagrossi, Carlotta Cerva, A. Battisti, Valentina Svicher, Raffaella Cerretti, Loredana Sarmati, Romina Salpini, Laura Cudillo, Benedetta Mariotti, and Gaetano Maffongelli
- Subjects
HBV reactivation ,Hbv DNA ,Hematopoietic stem cell transplantation ,Hepatitis B ,Prophylaxis ,Male ,0301 basic medicine ,Hepatitis B virus ,HBsAg ,Settore MED/17 - Malattie Infettive ,medicine.medical_treatment ,Case Report ,lcsh:Infectious and parasitic diseases ,Serology ,Immunocompromised Host ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Humans ,lcsh:RC109-216 ,Hepatitis B Antibodies ,Hepatitis B Surface Antigens ,business.industry ,Immunogenicity ,virus diseases ,Lamivudine ,Immunosuppression ,Antibiotic Prophylaxis ,Middle Aged ,medicine.disease ,Virology ,digestive system diseases ,Transplantation ,030104 developmental biology ,Infectious Diseases ,Immunology ,Virus Activation ,030211 gastroenterology & hepatology ,business ,medicine.drug - Abstract
Background HBV reactivation is associated with high mortality rates in hematopoietic stem cell transplantation (HSCT) and prophylactic lamivudine (LMV) treatment is suggested to prevent this phenomenon. However, the duration of LMV treatment in HSCT patients is not fully defined and the time of immune recovery is considered the best parameter for a drug to be safely interrupted. In patients undergoing allogeneic HSCT, the time of immune recovery is not easy to define and may take years after transplantation and prolonged LMV treatments, which can lead to drug-resistant viral strains. Case presentation An anti-HBc-positive hematological patient who was undergoing prolonged immunosuppression and who experienced HBV reactivation 3 months after the suspension of a prolonged LMV prophylaxis is described. HBV-DNA matching an atypical serological profile characterized by HbsAg negativity and anti-HBs positivity was detected in the patient. The genotypic analysis of the HBV strain identified T127P, F170FL and S204R mutations of HbsAg, which can hinder HBsAg recognition in a diagnostic assay. Conclusions HBV reactivation in the HSCT host can be sustained by HBsAg viral variants with characteristics of altered immunogenicity that cannot be detected by usual laboratory tests. This clinical case description suggests the importance of screening for serum HBV-DNA levels in the diagnosis of HBV reactivation and monitoring HBV-DNA after prophylaxis suspension, particularly in HSCT subjects who have undergone prolonged periods of LMV treatment.
- Published
- 2017
25. SAT-195-The novel HBx mutation F30V correlates with HCC in vivo, hampers HBV replicative efficiency and enhances anti-apoptotic activity of HBx N-terminus in vitro
- Author
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Jacopo Vecchiet, Angelica Sacco, Laura Belloni, L. Carioti, Alberto Spanò, Carlo Federico Perno, Pascale Trimoulet, Francesca Ceccherini Silberstein, G.A. Palumbo, Giuseppina Cappiello, Maria Francesca Cortese, Rossana Scutari, Caterina Pasquazzi, Mohammad Alkhatib, Romina Salpini, Gabriele Missale, Carmen Mirabelli, Massimo Levrero, Simona Francioso, Massimo Andreoni, Mario Angelico, Hervé Fleury, Loredana Sarmati, Valentina Svicher, and Matteo Surdo
- Subjects
N-terminus ,HBx ,Hepatology ,Apoptosis ,Chemistry ,In vivo ,Mutation (genetic algorithm) ,Molecular biology ,In vitro - Published
- 2019
26. SAT-193-Evolutionary relationship among hepatitis B virus genotype D in Latin America and Europe
- Author
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Carlo Federico Perno, Francesca Ceccherini Silberstein, Bibiane Armiliato de Godoy, Valentina Svicher, Nelson J. R. Fagundes, Romina Salpini, João Renato Rebello Pinho, and Michele Gomes
- Subjects
Latin Americans ,Hepatology ,Biology ,Hepatitis B virus genotype D ,Virology - Published
- 2019
27. SAT-196-The integrated use of highly sensitive HBV markers can predict HBV reactivation in HBsAg-negative/Anti-HBc positive patients from oncohematological setting
- Author
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L. Piermatteo, A. Battisti, Valentina Svicher, Carlotta Cerva, William Arcese, Romina Salpini, Angelica Sacco, Maria Cantonetti, Vincenzo Malagnino, Carlo Federico Perno, Loredana Sarmati, Massimo Andreoni, and Francesca Ceccherini Silberstein
- Subjects
Anti hbc ,Hbsag negative ,Hepatology ,business.industry ,Hbv reactivation ,Hbv markers ,Medicine ,business ,Virology ,Highly sensitive - Published
- 2019
28. Overlapping structure of hepatitis B virus (HBV) genome and immune selection pressure are critical forces modulating HBV evolution
- Author
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M. Bernassola, Guido Gubertini, Antonella d'Arminio Monforte, Valeria Cento, Xin Xin Zhang, Yue Han, Romina Salpini, Ada Bertoli, Pascale Trimoulet, Giuseppina Cappiello, Carlo Federico Perno, Jens Verheyen, Giuseppe Maria De Sanctis, Alberto Spanò, Salvatore Dimonte, Francesco Mazzotta, R. Longo, Valeria Micheli, Carmen Mirabelli, Valentina Svicher, and Francesca Ceccherini-Silberstein
- Subjects
Hepatitis B virus ,HBsAg ,Molecular Sequence Data ,Medizin ,HIV Infections ,Genome, Viral ,Biology ,medicine.disease_cause ,Evolution, Molecular ,Hepatitis B, Chronic ,Antigen ,Virology ,medicine ,Humans ,Amino Acid Sequence ,Gene ,Mutation ,Hepatitis B Surface Antigens ,Base Sequence ,Coinfection ,Genetic Variation ,HIV ,virus diseases ,RNA-Directed DNA Polymerase ,Hepatitis B ,medicine.disease ,Reverse transcriptase - Abstract
How the overlap between the hepatitis B virus (HBV) reverse transcriptase (RT) and HBV S antigen (HBsAg) genes modulates the extent of HBV genetic variability is still an open question, and was investigated here. The rate of nucleotide conservation (≤1 % variability) followed an atypical pattern in the RT gene, due to an overlap between RT and HBsAg (69.9 % nucleotide conservation in the overlapping region vs 41.2 % in the non-overlapping region; PP = 3.249×10−22]. The most conserved RT regions were located within the YMDD motif and the N-terminal parts of the palm and finger domains, critical for RT functionality. These regions also corresponded to highly conserved HBsAg domains that are critical for HBsAg secretion. Conversely, the genomic region encoding the HBsAg antigenic loop (where immune-escape mutations are localized) showed a sharp decrease in the extent of conservation (40.6 %), which was less pronounced in the setting of human immunodeficiency virus (HIV)-driven immune suppression (48.8 % in HIV–HBV co-infection vs 21.5 % in mono-infected patients; P = 0.020). In conclusion, the overlapping reading frame and the immune system appear to have shaped the patterns of RT and HBsAg genetic variability. Highly conserved regions in RT and HBsAg may deserve further attention as novel therapeutic targets.
- Published
- 2013
29. Late hepatitis B virus reactivation after lamivudine prophylaxis interruption in an anti-HBs-positive and anti-HBc-negative patient treated with rituximab-containing therapy
- Author
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Ada Bertoli, Valentina Svicher, Cesare Sarrecchia, Romina Salpini, Pasquale Sordillo, Loredana Sarmati, A. Ricciardi, Massimo Andreoni, Laura Ceccarelli, and Carlo Federico Perno
- Subjects
Microbiology (medical) ,Hepatitis B virus ,Mutation, Missense ,medicine.disease_cause ,Antiviral Agents ,Chemoprevention ,Virus ,Antibodies, Monoclonal, Murine-Derived ,Drug Therapy ,medicine ,Humans ,Hepatitis B Antibodies ,Aged ,biology ,business.industry ,virus diseases ,Lamivudine ,cccDNA ,Hepatitis B ,Settore MED/07 - Microbiologia e Microbiologia Clinica ,medicine.disease ,Virology ,digestive system diseases ,Discontinuation ,Infectious Diseases ,Withholding Treatment ,Immunology ,biology.protein ,Female ,Virus Activation ,Rituximab ,Antibody ,business ,medicine.drug - Abstract
We describe a case of an anti-HBs-positive patient who experienced hepatitis B reactivation 18 months after the discontinuation of rituximab and after 12 months of lamivudine prophylaxis. The patient carried a hepatitis B genotype D virus harbouring a single immune escape mutation, sT118K. No consensus guidelines regarding the optimal length of treatment or the best elective drug have been defined for antiviral prophylaxis for HBsAg-negative, anti-HBc- and/or anti-HBs-positive patients undergoing immunosuppressive treatment. Screening based on HBV serological markers and HBV DNA testing is a critical issue to recognise hepatitis B reactivation as early as possible. Furthermore, it is of outstanding importance to identify alternative markers (e.g. cccDNA, HBV core related antigen, etc.), that could be predictive of HBV reactivation.
- Published
- 2012
30. Characterization of drug resistance mutations in naïve and ART-treated patients infected with HIV-1 in Yaounde, Cameroon
- Author
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Romina Salpini, Maria Mercedes Santoro, Aubin Nanfack, Valeria Cento, Loredana Sarmati, Luca Dori, Massimo Andreoni, Vittorio Colizzi, Desire Takou, Carlo Federico Perno, Sylvie Moudourou, Judith N. Torimiro, Laura Ceccarelli, Joseph Fokam, and Giulia Cappelli
- Subjects
Adult ,Male ,Anti-HIV Agents ,Human immunodeficiency virus (HIV) ,HIV Infections ,Drug resistance ,medicine.disease_cause ,Virus ,Virology ,Drug Resistance, Viral ,Prevalence ,Humans ,Medicine ,Cameroon ,Treatment Failure ,Child ,Phylogeny ,Recombination, Genetic ,Mutation ,Genetic diversity ,business.industry ,Genetic Variation ,virus diseases ,HIV Protease Inhibitors ,Sequence Analysis, DNA ,Settore MED/07 - Microbiologia e Microbiologia Clinica ,Resistance mutation ,Regimen ,Cross-Sectional Studies ,Infectious Diseases ,pol Gene Products, Human Immunodeficiency Virus ,Child, Preschool ,Cohort ,HIV-1 ,Reverse Transcriptase Inhibitors ,Female ,business - Abstract
Currently the prevalence of HIV-1 infection in Cameroon is 5.1%, CRF02_AG subtype is responsible for about 50% of infections. Since an HIV-1 drug resistance test is not yet available widely, accurate data on the prevalence of resistant viral strains are missing. The objective of this study was to determine HIV-1 genetic diversity and to characterize HIV-1 mutations conferring drug resistance among antiretroviral therapy (ART)-naïve and ART-treated patients. A cohort of 239 patients infected with HIV were followed-up between January 2007 and July 2010 in Cameroon. Two hundred and sixteen plasma samples were sequenced for phylogenetic analysis and identification of drug resistance mutations in the HIV-1 pol region. A significant genetic diversity was found: Seven pure subtypes (A1, A3, D, F1, F2, G, H), nine circulating recombinant forms (CRFs: 01_AE, 02_AG, 06cpx, 09cpx, 11cpx, 13cpx, 16cpx, 18cpx, 37cpx) and one new unique recombinant form (URF) (G/F2). The rate of transmitted drug resistance (TDR) in naïve patients was 8.2% (4/49). Around 80% of patients failing a first-line ART harbored a virus with at least one resistance mutation to two antiretroviral (ARV) classes, and 36% of those failing a second-line regimen carried a virus with at least one resistant mutation to three ARV classes. The high level of drug resistance observed in the cohort is alarming because this occurred as a result of only few years of treatment. Adherence to therapy, adequate education of physicians, and the appropriate use of genotypic resistance assay are critical points of intervention for the improvement of patient care.
- Published
- 2012
31. Performance evaluation of an in-house human immunodeficiency virus type-1 protease-reverse transcriptase genotyping assay in Cameroon
- Author
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Carlo Federico Perno, Aubin Nanfack, Valeria Cento, Luc-Christian Gwom, Giulia Cappelli, Desire Takou, Vittorio Colizzi, Joseph Fokam, Maria Mercedes Santoro, Roberta D'Arrigo, Caterina Gori, and Romina Salpini
- Subjects
Adult ,Male ,Genotype ,Cost effectiveness ,Molecular Sequence Data ,HIV Infections ,03 medical and health sciences ,0302 clinical medicine ,Virology ,Humans ,Cameroon ,030212 general & internal medicine ,Typing ,Genetic variability ,Genotyping ,Phylogeny ,Aged ,030304 developmental biology ,Genetics ,0303 health sciences ,biology ,Genetic heterogeneity ,General Medicine ,Middle Aged ,Settore MED/07 - Microbiologia e Microbiologia Clinica ,biology.organism_classification ,HIV Reverse Transcriptase ,Reverse transcriptase ,3. Good health ,Genetic Techniques ,Lentivirus ,HIV-1 ,Female - Abstract
Most commercial HIV-1 genotyping assays are hampered by high cost in resource-limited settings. Moreover, their performance might be influenced over time by HIV genetic heterogeneity and evolution. An in-house genotyping protocol was developed, and its sequencing performance and reproducibility were compared to that of ViroSeq. One hundred ninety plasma samples from HIV-1-infected subjects in Cameroon, a resource-limited setting with a high HIV genetic variability, were processed for pol gene sequencing with an in-house protocol, ViroSeq, or both. Only non-B subtypes were found. The in-house sequencing performance was 98.7% against 92.1% with ViroSeq. Among 36 sequence pairs obtained using both assays, the overall rate of discordant amino acid positions was negligible (0.24%). With its high sensitivity and reproducibility, as well as its affordable cost (about half of ViroSeq: 92 euros vs. 217 euros), this in-house assay is a suitable alternative for HIV-1 genotyping in resource-limited and/or in high-genetic-diversity settings.
- Published
- 2011
32. Combination of HBV serological markers can predict the burden and productivity of intrahepatic HBV reservoir and disease progression in HBeAg-negative chronic hepatitis B infection
- Author
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Carlo Federico Perno, A. Battisti, N. Hansi, U.S. Gill, L. Colagrossi, Romina Salpini, L. Piermatteo, Patrick T F Kennedy, and Valentina Svicher
- Subjects
0301 basic medicine ,Hepatology ,business.industry ,0206 medical engineering ,Disease progression ,Gastroenterology ,02 engineering and technology ,020601 biomedical engineering ,Serology ,03 medical and health sciences ,030104 developmental biology ,Chronic hepatitis ,Hbeag negative ,Immunology ,Medicine ,business ,Productivity - Published
- 2018
33. Hepatitis B surface antigen genetic elements critical for immune escape correlate with hepatitis B virus reactivation upon immunosuppression
- Author
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Matteo Surdo, L. Carioti, Maria Concetta Bellocchi, Valentina Svicher, Claudio Maria Mastroianni, M. Paoloni, Claudia Alteri, L. Colagrossi, Yoram Louzoun, Romina Salpini, Mariarosaria Esposito, Michela Pollicita, Carlo Federico Perno, Loredana Sarmati, Massimo Andreoni, Mario Angelico, Massimo Marignani, Cesare Sarrecchia, Chiara D'Amore, Marianna Aragri, Christina Becker, Fabiola Di Santo, Aldo Marrone, Miriam Lichtner, A. Ricciardi, Daniele Armenia, Jens Verheyen, Salpini, R, Colagrossi, L, Bellocchi, Mc, Surdo, M, Becker, C, Alteri, C, Aragri, M, Ricciardi, A, Armenia, D, Pollicita, M, Di Santo, F, Carioti, L, Louzoun, Y, Mastroianni, Cm, Lichtner, M, Paoloni, M, Esposito, M, D'Amore, C, Marrone, A, Marignani, M, Sarrecchia, C, Sarmati, L, Andreoni, M, Angelico, M, Verheyen, J, Perno, Cf, Svicher, V, Marrone, Aldo, Verhejen, J, and Svicher, V.
- Subjects
Male ,HBsAg ,Glycosylation ,medicine.medical_treatment ,Medizin ,medicine.disease_cause ,genetic variability ,HBV ,education.field_of_study ,immunosuppression ,biology ,virus diseases ,Immunosuppression ,surface antigen ,Hepatitis B ,Middle Aged ,Settore MED/07 - Microbiologia e Microbiologia Clinica ,Rituximab ,Female ,Antibody ,medicine.drug ,Adult ,medicine.medical_specialty ,Hepatitis B virus ,Settore MED/17 - Malattie Infettive ,Population ,Hepatitis B, Chronic ,Internal medicine ,Drug Resistance, Viral ,medicine ,Humans ,Hepatitis B Antibodies ,education ,Aged ,Immune Evasion ,Immunosuppression Therapy ,Hepatitis B Surface Antigens ,Hepatology ,business.industry ,medicine.disease ,Virology ,digestive system diseases ,Immunology ,Mutation ,biology.protein ,Virus Activation ,business - Abstract
Hepatitis B virus (HBV) reactivation during immunosuppression can lead to severe acute hepatitis, fulminant liver failure, and death. Here, we investigated hepatitis B surface antigen (HBsAg) genetic features underlying this phenomenon by analyzing 93 patients: 29 developing HBV reactivation and 64 consecutive patients with chronic HBV infection (as control). HBsAg genetic diversity was analyzed by population-based and ultradeep sequencing (UDS). Before HBV reactivation, 51.7% of patients were isolated hepatitis B core antibody (anti-HBc) positive, 31.0% inactive carriers, 6.9% anti-HBc/anti-HBs (hepatitis B surface antibody) positive, 6.9% isolated anti-HBs positive, and 3.4% had an overt HBV infection. Of HBV-reactivated patients, 51.7% were treated with rituximab, 34.5% with different chemotherapeutics, and 13.8% with corticosteroids only for inflammatory diseases. In total, 75.9% of HBV-reactivated patients (vs. 3.1% of control patients; P
- Published
- 2015
34. Reliable timescale inference of HBV genotype A origin and phylodynamics
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Linda Bussini, Alessandra Lo Presti, Claudia Alteri, Massimo Ciccozzi, Carlo Federico Perno, Elisabetta Tanzi, Alessia Lai, Erika Ebranati, Elena Gabanelli, Eleonora Cella, Marta Giovanetti, Massimo Galli, Romina Salpini, Gianguglielmo Zehender, Valentina Svicher, and Carla Veo
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Microbiology (medical) ,Hepatitis B virus ,Latin Americans ,Asia ,Genes, Viral ,Genotype ,Evolution ,Ethnic group ,HBV genotype A ,HBV subgenotype A1 ,HBV subgenotype A2 ,Molecular clock calibration ,Phylogeography ,Africa ,Calibration ,Chromosome Mapping ,Europe ,Genetic Variation ,Hepatitis B ,Humans ,Phylogeny ,Sequence Analysis, DNA ,Evolution, Molecular ,Biology ,medicine.disease_cause ,Microbiology ,Settore MED/07 ,Genetics ,medicine ,Viral ,Clade ,Molecular Biology ,Ecology, Evolution, Behavior and Systematics ,Ancestor ,Molecular ,DNA ,Virology ,language.human_language ,Genealogy ,Infectious Diseases ,Viral phylodynamics ,Genes ,language ,Portuguese ,Sequence Analysis - Abstract
The worldwide distributed Hepatitis B virus (HBV) genotype A is classified into three subgenotypes, and one quasi-subgenotype. The majority of HBV-A subgenotypes are widespread in Africa and in ethnic groups that have relatively recently emigrated from African countries, whereas HBV-A2 is highly prevalent among subjects at high risk for sexual exposure to HBV in north-western Europe and the USA. The aim of this study was to reconstruct the origin and dispersion of HBV-A subgenotypes on a reliable timescale using short-term calibration based on heterochronous sampling for HBV-A2, and long-term calibration based on historical data for the other subgenotypes. To this aim, we analysed 113 newly characterised HBV-A isolates with 247 reference sequences retrieved from a public database. The phylodynamic reconstruction was performed by a Bayesian framework. The common ancestor of the currently circulating A subgenotypes was placed in west-central Africa a mean 1057 years ago. The genotype diverged into two main clades at the beginning of the 13th century: one including all of the west-central African quasi-subgenotypes and the other corresponding to subgenotype A1, originating in east Africa and further segregating into two main subclades: an "African" and a "cosmopolitan" clade. It is likely that the slave trade was the main source the spread of cosmopolitan HBV-A1, which was exported to Asia in the 17th century as a result of Arab or Portuguese trade, and to Latin America in the 18th centuries through the trans-Atlantic slave trade. The origin of the currently circulating A2 strains dates back to the first decades of the 20th century, and the evolutionary demography analysis suggests an exponential growth of infections, between 1970s and the mid-1990s. In conclusion, the very different epidemiological and evolutionary histories of HBV-A subgenotypes justify the use of different calibration approaches to reconstruct their reciprocal phylodynamics.
- Published
- 2014
35. Vaccine-escape HBsAg mutants circulating among genotype D HBV-infected patients correlate with atypical serological profiles, high viremia and transaminases: Potential impact on vaccination strategies
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Domenico Di Carlo, Giuseppina Cappiello, M. Paoloni, Claudio Maria Mastroianni, Giustino Parruti, T. Mari, Claudio Puoti, L. Colagrossi, I. Vecchiet, Romina Salpini, Valentina Svicher, A. Battisti, Cesare Sarrecchia, Caterina Pasquazzi, Alberto Spanò, N. Iapadre, D. Di Paolo, Massimo Marignani, Michela Pollicita, S. Romano, Lavinia Fabeni, Miriam Lichtner, Claudia Alteri, M. Visca, G. De Sanctis, Massimo Andreoni, Mario Angelico, C.F. Perno, and Aldo Bertoli
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Potential impact ,HBsAg ,Hepatology ,business.industry ,Mutant ,Gastroenterology ,Viremia ,medicine.disease ,Virology ,Serology ,Vaccination ,Immunology ,Genotype ,Vaccine escape ,Medicine ,business - Published
- 2016
36. Immunosuppression-driven HBV reactivation in patients with resolved HBV infection correlates with a relevant risk of death and with evolution towards active chronical infection
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Claudia Alteri, Simona Francioso, Massimo Marignani, D. Di Paolo, Valentina Svicher, L. Colagrossi, Claudio Maria Mastroianni, A. Brega, Massimo Andreoni, Mario Angelico, E. Mazzoni, K. Casinelli, Carlotta Cerva, Gloria Taliani, Aldo Marrone, Filomena Morisco, Loredana Sarmati, C.F. Perno, Cesare Sarrecchia, N. Iapadre, Romina Salpini, M. Paoloni, T. Mari, Miriam Lichtner, Michela Pollicita, Gaetano Maffongelli, Constance Delaugerre, Sarah Maylin, Nicola Coppola, Adriano Venditti, A. Ricciardi, and A. Battisti
- Subjects
Hepatology ,business.industry ,medicine.medical_treatment ,Gastroenterology ,medicine ,Hbv reactivation ,Immunosuppression ,In patient ,Risk of death ,business ,Virology - Published
- 2016
37. P0614 : Key HBsAg mutations significantly correlate with HCC, hamper HBsAg secretion and promote cell proliferation in vitro
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S. Romano, Gabriele Missale, Cesare Sarrecchia, J. Vecchiet, Matteo Surdo, Alberto Spanò, Michela Pollicita, Danni Colledge, Francesca Ceccherini-Silberstein, A. Barlattani, Romina Salpini, C.F. Perno, T. Mari, Simona Francioso, Aldo Bertoli, Nadia Warner, Valentina Svicher, Caterina Pasquazzi, Hervé Fleury, N. Iapadre, Stephen Locarnini, Sally Soppe, Elisa Orecchini, Massimo Andreoni, R. Longo, Mario Angelico, Carmen Mirabelli, Pascale Trimoulet, Giuseppina Cappiello, Alessandro Michienzi, and Maria Francesca Cortese
- Subjects
HBsAg ,Hepatology ,Cell growth ,Immunology ,Secretion ,Biology ,In vitro - Published
- 2015
38. Detecting Hepatitis B Viral Amino Acid Sequence Mutations in Occult Hepatitis B Infections via Bayesian Partition Model
- Author
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Valeria Cento, Valentina Svicher, Romina Salpini, Jing Zhang, Qi Ning Tian, Yang Liu, Gang Chen, Carlo Federico Perno, Cong Li, and Zhichao Lian
- Subjects
chemistry.chemical_classification ,Hepatitis B virus ,HBsAg ,Cell Biology ,Biology ,Hepatitis B ,medicine.disease ,medicine.disease_cause ,Biochemistry ,Virology ,Reverse transcriptase ,Computer Science Applications ,Amino acid ,Pathogenesis ,chemistry ,Genotype ,medicine ,Molecular Biology ,Peptide sequence - Abstract
Background: With advancements in technology, a number of Hepatitis B virus (HBV) infections, where viral DNA is present in the liver or plasma, without the concomitant detection of HBsAg in plasma have been reported, and have been termed occult Hepatitis B infections (OBI). Unfortunately, the etiology and pathogenesis of OBI remain elusive to date, and the genetic characteristics of HBV sequence that lead to the development of OBI are still poorly understood. Methods: 358 genotype-C (330 chronically infected patients and 28 occult infected patients) and 107 genotype-D (83 chronically infected patients and 24 occult infected patients) HBV Reverse Transcriptase (RT) amino acid sequences were collected. In addition to greedy search, a novel statistical approach, Bayesian Variable Partition Model is applied to pinpoint those positions, where amino acid mutations collaboratively discriminate OBI samples from chronically infected samples, in genotype-C and genotype-D, respectively. Results: Several discriminate and correlated positions were found in genotype-C (high-order position combinations listed in tables) and genotype-D (positions 126+138, 129+131 and 138+139) respectively. By comparing amino acid distributions in these positions between genotype-C and genotype-D, six position combinations were reported to have obvious different amino acid distributions in these two HBV genotypes. Conclusions: This paper furthers the understanding of the correlation between HBV sequence mutations and the differences of OBI in two HBV genotypes, by studying mutations in HBV RT amino acid sequences. Different from other traditional methods, the Bayesian-based method is able to analyze high-order combinations of positions.
- Published
- 2013
39. HBsAg mutations correlated with HCC in vivo affect HBsAg release and favor cell proliferation in vitro
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Michela Pollicita, Stephen Locarnini, T. Mari, Aldo Bertoli, C.F. Perno, Danni Colledge, Matteo Surdo, Carmen Mirabelli, Romina Salpini, Francesca Ceccherini-Silberstein, Simona Francioso, Hervé Fleury, N. Iapadre, Patrizia Saccomandi, Pascale Trimoulet, Alessandro Michienzi, S. Romano, Cesare Sarrecchia, Maria Francesca Cortese, Elisa Orecchini, Massimo Andreoni, Mario Angelico, Caterina Pasquazzi, Alberto Spanò, J. Vecchiet, Valentina Svicher, A. Barlattani, Gabriele Missale, Nadia Warner, R. Longo, Giuseppina Cappiello, and Sally Soppe
- Subjects
Hepatology ,business.industry ,Gastroenterology ,Medicine ,Reference laboratory ,Ancient history ,business ,University hospital ,Virology - Abstract
R. Salpini1, M. Surdo1, N. Warner2, M.F. Cortese1, C. Mirabelli 1,3, D. Colledge2, S. Soppe2, P. Saccomandi1, M. Pollicita1, R. Longo4, S. Romano4, G. Cappiello4, A. Spano4, P. Trimoulet5, H. Fleury5, J. Vecchiet6, N. Iapadre7, A. Barlattani8, A. Bertoli 1, T. Mari9, C. Pasquazzi10, G. Missale11, C. Sarrecchia12, E. Orecchini13, A. Michienzi13, M. Andreoni12, S. Francioso14, M. Angelico14, F. Ceccherini-Silberstein1, S. Locarnini2, C.F. Perno1, V. Svicher1 1 Department of Experimental Medicine, University of Rome “Tor Vergata” Rome, Italy 2 Research and Molecular Development, Victorian Infectious Diseases Reference Laboratory, North Melbourne, Victoria, Australia 3 Institut Pasteur, Unite de Biologie des virus enteriques, 25 rue du Dr Roux, 75015 Paris, France 4 S. Pertini Hospital”, Rome, Italy 5 Hopital Pellegrin Tripode, Bordeaux, France 6 SS Annunziata” Hospital, Chieti, Italy 7 S Salvatore” Hospital, L’Aquila, Italy 8 “S Giacomo” Hospital, Rome, Italy 9 “Regina Margherita” Hospital, Rome, Italy 10 “S Andrea” Hospital, Rome, Italy 11 Hospital of Parma, Parma, Italy 12 Tor Vergata University Hospital, Infectious Diseases Unit, Rome, Italy 13 Department of Biomedicine and Prevention, University of Rome “Tor Vergata” Rome, Italy 14 Tor Vergata University Hospital, Hepatology Unit, Rome, Italy
- Published
- 2016
40. A recent epidemiological cluster of acute hepatitis B genotype F1b infection in a restricted geographical area of Italy
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A. Ranelli, Giustino Parruti, Carlo Federico Perno, M. Dalessandro, Claudia Alteri, A. Battisti, Maria Concetta Bellocchi, M. Paoloni, Daniele Armenia, Valentina Svicher, Romina Salpini, L. Colagrossi, Marianna Aragri, R. Mariani, L. Carioti, Michela Pollicita, and Lavinia Fabeni
- Subjects
Adult ,Male ,Microbiology (medical) ,Hepatitis B virus ,medicine.medical_specialty ,Unprotected Sexual Intercourse ,Sexual transmission ,genotype ,medicine.disease_cause ,Disease cluster ,vaccine ,Genotype ,Epidemiology ,HBV ,Humans ,Medicine ,Phylogeny ,epidemiological cluster ,business.industry ,High-Throughput Nucleotide Sequencing ,Acute infection ,Sequence Analysis, DNA ,Sexually Transmitted Diseases, Viral ,General Medicine ,Middle Aged ,Hepatitis B ,Settore MED/07 - Microbiologia e Microbiologia Clinica ,medicine.disease ,Virology ,Vaccination ,Phylogeography ,Infectious Diseases ,Italy ,DNA, Viral ,Immunology ,Female ,business - Abstract
In this study, by phylogenetic analysis, we identified an epidemiological cluster involving eight individuals diagnosed with acute hepatitis B virus (HBV) infection related to unprotected sexual intercourse in a restricted area of central Italy (time period: 2011–2014). Notably, these patients (six of eight Italians) were infected by subgenotype F1b, which is not commonly found in western countries. Ultra-deep pyrosequencing confirmed a superimposable composition of HBV quasi-species in these patients. Despite the availability of effective vaccination, this study highlights the importance of not underestimating the risk of HBV infection, of continuing to set up surveillance programmes for HBV infection, and of investigating the pathogenetic potential of these atypical genotypes.
- Published
- 2015
41. HIV-2 A-subtype gp125c₂-v₃-c₃ mutations and their association with CCR5 and CXCR4 tropism
- Author
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Salvatore, Dimonte, Valentina, Svicher, Romina, Salpini, Francesca, Ceccherini-Silberstein, Carlo-Federico, Perno, and Muhammed, Babakir-Mina
- Subjects
Receptors, CXCR4 ,Viral Tropism ,Receptors, CCR5 ,Amino Acid Motifs ,HIV-2 ,Mutation ,env Gene Products, Human Immunodeficiency Virus ,Humans ,Receptors, Virus ,HIV Infections ,Protein Binding - Abstract
The early events of the HIV replication cycle involve the interaction between viral envelope glycoproteins and their cellular CD4-chemokine (CCR5/CXCR4) receptor complex. In this study, for the first time, the HIV-2 A-subtype gp125(C2-V3-C3) mutations and their tropism association were characterized by analyzing 149 HIV-2 sequences from the Los Alamos database. The analysis has strengthened the importance of C2-V3-C3 region as a determinant factor for co-receptor selection. Moreover, statistically significant correlations were observed between C2-V3-C3 mutations, and several correlated mutations were associated with CXCR4 and CCR5 co-receptor usage. A dendrogram showed two distinct clusters, with numerous associated mutations grouped, thus dividing CCR5- and CXCR4-tropic viruses. Fourteen X4-tropic virus mutations, all in V3 and C3 domains and forming highly significant subclusters, were found. Finally, R5 associations, two strong subclusters were observed, grouping several C2-V3-C3 mutated positions. These data indicate the possible contribution of C2-V3-C3 mutational patterns in regulating HIV-2 tropism.
- Published
- 2011
42. The profile of mutational clusters associated with lamivudine resistance can be constrained by HBV genotypes
- Author
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Maria Trignetti, Alberto Spanò, Valeria Micheli, Valentina Svicher, Francesca Ceccherini-Silberstein, Romina Salpini, M. Bernassola, Fosca Niero, Caterina Gori, Guido Gubertini, Giuseppe Maria De Sanctis, R. Longo, Carlo Federico Perno, M. Visca, and Giuseppina Cappiello
- Subjects
Adult ,HBsAg ,Hepatitis B virus ,Genotype ,Drug Resistance ,HIV Infections ,Biology ,medicine.disease_cause ,Antiviral Agents ,Polymerase Chain Reaction ,Hepatitis B, Chronic ,Telbivudine ,Drug Resistance, Viral ,Adefovir ,medicine ,Cluster Analysis ,Humans ,Viral ,Aspartate Aminotransferases ,Chronic ,DNA Primers ,Genetics ,Mutation ,Hepatology ,Lamivudine ,Alanine Transaminase ,RNA-Directed DNA Polymerase ,DNA ,Middle Aged ,Hepatitis B ,Settore MED/07 - Microbiologia e Microbiologia Clinica ,Virology ,Reverse transcriptase ,Amino Acid Substitution ,DNA, Viral ,medicine.drug - Abstract
Background/Aims To investigate the different clusters of mutations associated with lamivudine resistance in HBV genotypes D and A. Methods HBV reverse transcriptase sequences of 89 HBV-infected patients failing lamivudine treatment were analyzed. The association of mutations with HBV genotypes was assessed by Chi-Squared test and multivariate logistic regression analysis. Covariate analysis was based on hierarchical clustering. Results In genotype A, the rtM204V (prevalence: 68.2%) was the main sign of lamivudine failure. Multivariate analysis confirmed that genotype A is the only predictor for rtM204V emergence (OR: 14.5 [95% CI: 1.3–158], P =0.02). Covariate analysis showed that rtM204V clusters with rtL180M, rtL229V (corresponding to sF220L in the HBsAg), and, interestingly, with HBsAg mutation sS207N (bootstrap=0.95). Both sF220L and sS207N co-localized in the fourth transmembrane HBsAg domain. In contrast, in genotype D the primary mutations rtM204V and rtM204I occurred with similar prevalence (39.1% versus 45.3%, P =0.47), and showed a distinct pattern of compensatory mutations. rtM204V clusters with mutations localized in the RT-B domain (rtV173L, rtL180M, and rtT184A/S) (bootstrap=0.94), while rtM204I clusters with mutations localized in the RT-A domain (rtS53N, rtT54Y, and rtL80I/V) (bootstrap=0.96) (without associations with HBsAg specific mutations). Conclusions HBV genotype plays an important role in driving RT evolution under lamivudine treatment, and thus can be relevant for therapeutic sequencing, immunological response and disease progression.
- Published
- 2008
43. P0580 : Genetic signatures specifically clustered in immune active HBsAg regions correlate with immunosuppression-driven HBV reactivation: An extensive analysis of HBV genome
- Author
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Miriam Lichtner, Loredana Sarmati, Valentina Svicher, Cesare Sarrecchia, F. Di Santo, Filomena Morisco, A. Battisti, Daniele Armenia, Sarah Maylin, D. Di Paolo, Nicola Coppola, Romina Salpini, A. Ricciardi, L. Carioti, Michela Pollicita, Massimo Marignani, L. Colagrossi, Maria Concetta Bellocchi, Claudio Maria Mastroianni, Massimo Andreoni, Mario Angelico, Claudia Alteri, C.F. Perno, Aldo Marrone, M. Paoloni, and Constance Delaugerre
- Subjects
HBsAg ,Immune system ,Hepatology ,medicine.medical_treatment ,medicine ,Hbv reactivation ,Immunosuppression ,Biology ,Genome ,Virology - Published
- 2015
44. P0625 : A hyper-glycosylation of HBV surface major hydrophilic region characterizes HBV reactivation driven by immunosuppression and affects HBsAg recognition in vitro
- Author
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Michela Pollicita, C.F. Perno, F. Di Santo, M. Andreoni, Massimo Marignani, L. Colagrossi, A. Battisti, Aldo Marrone, Valentina Svicher, Sarah Maylin, Mario Angelico, Jens Verheyen, Nicola Coppola, Claudio Maria Mastroianni, Constance Delaugerre, Romina Salpini, Aldo Bertoli, L. Sarmati, Matteo Surdo, Filomena Morisco, and C. Becker
- Subjects
HBsAg ,chemistry.chemical_compound ,Glycosylation ,Hepatology ,Chemistry ,medicine.medical_treatment ,Immunology ,medicine ,Hbv reactivation ,Immunosuppression ,Virology ,In vitro - Published
- 2015
45. P0628 : A high genetic heterogeneity in HBsAg can affect immunogenicity in acute hepatitis B infection
- Author
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Caterina Sagnelli, Romina Salpini, Nicola Coppola, L. Carioti, Mariantonietta Pisaturo, Maria Concetta Bellocchi, C.F. Perno, Claudia Alteri, Marianna Aragri, Mario Starace, Valentina Svicher, Michela Pollicita, A. Battisti, Daniele Armenia, and Evangelista Sagnelli
- Subjects
HBsAg ,Hepatology ,Genetic heterogeneity ,business.industry ,Immunogenicity ,Medicine ,Acute hepatitis B ,Affect (psychology) ,business ,Virology - Published
- 2015
46. A high HBsAg genetic complexity can influence HBV immunogenicity in the setting of acute infection
- Author
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Claudia Alteri, Mariantonietta Pisaturo, A. Battisti, Marianna Aragri, Evangelista Sagnelli, Valentina Svicher, Maria Concetta Bellocchi, Mario Starace, C.F. Perno, Romina Salpini, Nicola Coppola, L. Carioti, Caterina Sagnelli, Michela Pollicita, Daniele Armenia, Battisti, A, Aragri, M, Coppola, N, Alteri, C, Sagnelli, C, Pisaturo, M, Bellocchi, Mc, Salpini, R, Starace, M, Armenia, D, Carioti, L, Pollicita, M, Sagnelli, E, Perno, Cf, and Svicher, V
- Subjects
Genetic complexity ,medicine.medical_specialty ,HBsAg ,Hepatology ,business.industry ,Family medicine ,Immunogenicity ,Gastroenterology ,Medicine ,Acute infection ,business ,Virology ,Mental health - Abstract
A. Battisti 1, M. Aragri1, N. Coppola2, C. Alteri1, C. Sagnelli 3, M. Pisaturo2, M.C. Bellocchi1, R. Salpini1, M. Starace2, D. Armenia1, L. Carioti 1, M. Pollicita1, E. Sagnelli 2, C.F. Perno1, V. Svicher1 1 Department of Experimental Medicine and Surgery, University of Rome “Tor Vergata”, Rome, Italy 2 Department of Mental Health and Public Medicine, Section of Infectious Diseases, Second University of Naples, Naples, Italy 3 Department of Clinical and Experimental Medicine and Surgery, Second University of Naples, Naples, Italy
- Published
- 2015
47. HBsAg genetic elements critical for immune escape correlates with HBV reactivation upon immunosuppression
- Author
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M. Paoloni, Michela Pollicita, F. Di Santo, Claudia Alteri, Yoram Louzoun, Aldo Marrone, Claudio Maria Mastroianni, C.F. Perno, Daniele Armenia, Aldo Bertoli, L. Colagrossi, Cesare Sarrecchia, Valentina Svicher, A. Ricciardi, Loredana Sarmati, Massimo Andreoni, Mario Angelico, Maria Concetta Bellocchi, Romina Salpini, Fabio Continenza, and L. Carioti
- Subjects
HBsAg ,Hepatology ,business.industry ,medicine.medical_treatment ,Immunology ,Gastroenterology ,medicine ,Hbv reactivation ,Immune escape ,Immunosuppression ,business - Published
- 2014
48. Key genetic markers in the full-length HBsAg gene correlate with HBV-driven carcinogenesis by affecting HBsAg secretion and release
- Author
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Caterina Gori, Pascale Trimoulet, Aldo Bertoli, Valeria Micheli, Valentina Svicher, Carmen Mirabelli, T. Mari, Fosca Niero, Valeria Cento, A. Salso, Gabriele Missale, Carlo Magni, J. Vecchiet, M. Santoro, Francesca Ceccherini-Silberstein, Claudia Alteri, Michela Pollicita, Maria Neumann-Fraune, A. Barlattani, J. Verhejen, Marianna Aragri, Guido Gubertini, C.F. Perno, Giuliano Rizzardini, Massimo Andreoni, Mario Angelico, Caterina Pasquazzi, Romina Salpini, V.C. Di Maio, Cesare Sarrecchia, Hervé Fleury, and N. Iapadre
- Subjects
HBsAg ,Hepatology ,Genetic marker ,business.industry ,Immunology ,Gastroenterology ,Medicine ,Secretion ,business ,Carcinogenesis ,medicine.disease_cause ,Gene ,Virology - Published
- 2014
49. HCV Genotypes Are Differently Prone to the Development of Resistance to Linear and Macrocyclic Protease Inhibitors
- Author
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Carmen Mirabelli, Francesca Ceccherini-Silberstein, Stefano Alcaro, Salvatore Dimonte, Fabio Mercurio, Cesare Sarrecchia, Ada Bertoli, Anna Artese, Valeria Cento, Giosuè Costa, Massimo Andreoni, Mario Angelico, Lucia Parrotta, Carlo Federico Perno, Marco Ciotti, Valentina Svicher, Romina Salpini, and Daniele Di Paolo
- Subjects
Gastroenterology and hepatology ,Protein Conformation ,HCV genotypes ,lcsh:Medicine ,1 INFECTION ,Hepacivirus ,Viral Nonstructural Proteins ,Hepatitis ,HEPATITIS-C-VIRUS ,DRUG-RESISTANCE ,GENETIC BARRIER ,NS3/4A PROTEASE ,PEGINTERFERON ALPHA-2B ,ANTIVIRAL EFFICACY ,PLUS RIBAVIRIN ,TELAPREVIR ,REPLICATION ,lcsh:Science ,Settore MED/12 - Gastroenterologia ,Multidisciplinary ,virus diseases ,Settore MED/07 - Microbiologia e Microbiologia Clinica ,Hepatitis C ,Molecular Docking Simulation ,Infectious hepatitis ,Medicine ,Infectious diseases ,RNA, Viral ,Christian ministry ,Research Article ,Drugs and Devices ,Drug Research and Development ,Genotype ,Molecular Sequence Data ,Library science ,Viral diseases ,Biology ,Antiviral Agents ,Viral genetics ,Genetic Mutation ,Drug Resistance, Viral ,Genetics ,Humans ,Protease Inhibitors ,Mutation detection ,Amino Acid Sequence ,Liver diseases ,Competing interests ,lcsh:R ,Genetic Variation ,Virology ,digestive system diseases ,Amino acid sequence analysis ,Nucleic Acid Conformation ,lcsh:Q ,Sequence Alignment - Abstract
BACKGROUND: Because of the extreme genetic variability of hepatitis C virus (HCV), we analyzed whether specific HCV-genotypes are differently prone to develop resistance to linear and macrocyclic protease-inhibitors (PIs). METHODS: The study includes 1568 NS3-protease sequences, isolated from PI-naive patients infected with HCV-genotypes 1a (N = 621), 1b (N = 474), 2 (N = 72), 3 (N = 268), 4 (N = 54) 5 (N = 6), and 6 (N = 73). Genetic-barrier was calculated as the sum of nucleotide-transitions (score = 1) and/or nucleotide-transversions (score = 2.5) required for drug-resistance-mutations emergence. Forty-three mutations associated with PIs-resistance were analyzed (36A/M/L/G-41R-43S/V-54A/S/V-55A-Q80K/R/L/H/G-109K-138T-155K/Q/T/I/M/S/G/L-156T/V/G/S-158I-168A/H/T/V/E/I/G/N/Y-170A/T-175L). Structural analyses on NS3-protease and on putative RNA-models have been also performed. RESULTS: Overall, NS3-protease was moderately conserved, with 85/181 (47.0%) amino-acids showing 94% HCV-2-4; 175L present in 100% HCV-1a-3-5 and >97% HCV-2-4). Furthermore, HCV-3 specifically showed non-conservative polymorphisms (R123T-D168Q) at two drug-interacting positions. Regardless of HCV-genotype, 13 PIs resistance-mutations were associated with low genetic-barrier, requiring only 1 nucleotide-substitution (41R-43S/V-54A-55A-80R-156V/T: score = 1; 54S-138T-156S/G-168E/H: score = 2.5). By contrast, by using HCV-1b as reference genotype, nucleotide-heterogeneity led to a lower genetic-barrier for the development of some drug-resistance-mutations in HCV-1a (36M-155G/I/K/M/S/T-170T), HCV-2 (36M-80K-155G/I/K/S/T-170T), HCV-3 (155G/I/K/M/S/T-170T), HCV-4-6 (155I/S/L), and HCV-5 (80G-155G/I/K/M/S/T). CONCLUSIONS: The high degree of HCV genetic variability makes HCV-genotypes, and even subtypes, differently prone to the development of PIs resistance-mutations. Overall, this can account for different responsiveness of HCV-genotypes to PIs, with important clinical implications in tailoring individualized and appropriate regimens.
- Published
- 2012
50. 197 Population Level Drug Resistance Mutations in HIV Type 1 Protease and Reverse Transcriptase in Cameroon: 1995 to 2010 Review
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Judith N. Torimiro, Romina Salpini, Desire Takou, Giulia Cappelli, Carlo Federico Perno, Joseph Fokam, Aubin Nanfack, and Vittorio Colizzi
- Subjects
Infectious Diseases ,Protease ,Population level ,business.industry ,medicine.medical_treatment ,Human immunodeficiency virus (HIV) ,Medicine ,Pharmacology (medical) ,Drug resistance ,business ,medicine.disease_cause ,Virology ,Reverse transcriptase - Published
- 2011
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