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Introduction: Human respiratory syncytial virus (hRSV) is a main cause of bronchiolitis in infants and its persistence has been described in immunocompromised subjects. However, limited evidence has been reported on the gene expression triggered by the hRSV and the effect of recombinant Taenia solium-derived calreticulin (rTsCRT). Methods: Using a comprehensive microarray approach, we analyzed the transcriptome profile of a macrophage cell line that has supported hRSV persistence for over 150 passages. We compared the gene expression of persistently infected and non-infected macrophages. We also evaluated the effect of rTsCRT on hRSV-infected macrophage gene transcription, as well as on cytokine production and number of copies of the persistent hRSV genome. Results: Our analysis showed that hRSV long-term virus infection significantly alters mRNA expression of antiviral, inflammatory, as well as arginine and lipid metabolism-associated genes, revealing a transcriptional signature that suggests a mixed M1/M2 phenotype. The resulting host-virus equilibrium allows for the regulation of viral replication, while evading the antiviral and proinflammatory responses. Interestingly, rTsCRT stimulus upregulated Tnfα, Il6 and Nos2 mRNA. We found increased levels of both proinflammatory cytokines and nitrite levels in the conditioned media of persistent macrophages treated with rTsCRT. This increase was associated with a significant reduction in viral genome copies. Discussion: hRSV persistently infected macrophages retain responsiveness to external stimuli and demonstrate that the profound changes induced by viral persistence are potentially reversible. Our observations contribute to the understanding of the mechanisms related to hRSV persistence in macrophages and have implications for the development of targeted therapies to eliminate persistent infections or reduce the negative effects related with chronic inflammatory diseases associated with hRSV infection. [ABSTRACT FROM AUTHOR]

Antivirals with proven effectiveness against the Omicron SARS-CoV-2 variant are required for COVID-19 treatment in hospitalized patients, particularly those with severe underlying conditions. Ensitrelvir, a 3C-like protease inhibitor, received emergency approval in Japan in November 2022, based on evidence of rapid symptom resolution in non-hospitalized patients, but confirmation of its effectiveness in hospitalized patients is lacking. This retrospective chart review reports outcomes for all patients who received ensitrelvir whilst hospitalized with SARS-CoV-2 infection at Rinku General Medical Center, Japan (November 2022–April 2023). Thirty-two hospitalized patients received 5 days of ensitrelvir treatment (375 mg loading dose, 125 mg as maintenance dose). Patients' mean age was 73.5 years and most had mild COVID-19. Patients exhibited various underlying diseases, most commonly hypertension (78.1%) and chronic kidney disease (25.0%). Seven (21.9%) patients were on hemodialysis. The most common concomitant medications were antihypertensives (59.4%) and corticosteroids (31.3%); 2 (6.3%) patients were being treated with rituximab; 28 (87.5%) patients had viral persistence following pre-treatment by remdesivir. Following ensitrelvir treatment, viral clearance was recorded in 18 (56.3%) patients by Day 6 and 25 (78.1%) patients at final measurement. All patients experienced clinical improvement as assessed by the investigator at Day 5. No intensive care unit admissions or deaths due to COVID-19 occurred. No new safety signals were observed. In conclusion, positive virological outcomes were observed following ensitrelvir treatment, in hospitalized patients with SARS-CoV-2 in a real-world setting, including high-risk patients, who failed previous antiviral therapy. These results require confirmation in more extensive studies. UMIN000051300. [ABSTRACT FROM AUTHOR]

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Zika virus (ZIKV), a mosquito-borne flavivirus, is a significant global health concern due to its association with neurodevelopmental disorders such as congenital Zika syndrome (CZS). This study aimed to compare the replication kinetics, viral persistence, cytopathogenic effects, and immune gene expression in human microglia cells (CHME-3) infected with an Asian lineage ZIKV (PRVABC59, referred to as ZIKV-PRV) and an African lineage ZIKV (IBH30656, referred to as ZIKV-IBH). We found that ZIKV-PRV replicated more efficiently and persisted longer while inducing lower levels of cell death and inflammatory gene activation compared with ZIKV-IBH. These findings suggest that the enhanced replication and persistence of ZIKV-PRV, along with its ability to evade innate immune responses, may underlie its increased neuropathogenic potential, especially in the context of CZS. In contrast, ZIKV-IBH, with its stronger immune gene activation and higher cytopathogenicity, may lead to more acute infections with faster viral clearance, thereby reducing the likelihood of chronic central nervous system (CNS) infection. This study provides crucial insights into the molecular and cellular mechanisms driving the differential pathogenicity of ZIKV lineages and highlights the need for further research to pinpoint the viral factors responsible for these distinct clinical outcomes. [ABSTRACT FROM AUTHOR]

Viral hepatitis is a major cause of liver illness worldwide. Despite advances in the understanding of these infections, the pathogenesis of hepatitis remains a complex process driven by intricate interactions between hepatitis viruses and host cells at the molecular level. This paper will examine in detail the dynamics of these host–pathogen interactions, highlighting the key mechanisms that regulate virus entry into the hepatocyte, their replication, evasion of immune responses, and induction of hepatocellular damage. The unique strategies employed by different hepatitis viruses, such as hepatitis B, C, D, and E viruses, to exploit metabolic and cell signaling pathways to their advantage will be discussed. At the same time, the innate and adaptive immune responses put in place by the host to counter viral infection will be analyzed. Special attention will be paid to genetic, epigenetic, and environmental factors that modulate individual susceptibility to different forms of viral hepatitis. In addition, this work will highlight the latest findings on the mechanisms of viral persistence leading to the chronic hepatitis state and the potential implications for the development of new therapeutic strategies. Fully understanding the complex host–pathogen interactions in viral hepatitis is crucial to identifying new therapeutic targets, developing more effective approaches for treatment, and shedding light on the mechanisms underlying progression to more advanced stages of liver damage. [ABSTRACT FROM AUTHOR]

Long COVID (post-acute sequelae of COVID-19—PASC) is a consequence of infection by SARS-CoV-2 that continues to disrupt the well-being of millions of affected individuals for many months beyond their first infection. While the exact mechanisms underlying PASC remain to be defined, hypotheses regarding the pathogenesis of long COVID are varied and include (but are not limited to) dysregulated local or systemic inflammatory responses, autoimmune mechanisms, viral-induced hormonal imbalances, skeletal muscle abnormalities, complement dysregulation, novel abzymes, and long-term persistence of virus and/or fragments of viral RNA or proteins. This review article is based on a comprehensive review of the wide range of symptoms most often observed in long COVID and an attempt to integrate that information into a plausible hypothesis for the pathogenesis of PASC. In particular, it is proposed that long-term dysregulation of the gut in response to viral persistence could lead to the myriad of symptoms observed in PASC. [ABSTRACT FROM AUTHOR]

Long COVID, now unmistakably identified as a syndromic entity encompassing a complex spectrum of symptoms, demands immediate resolution of its elusive pathogenic underpinnings. The intricate interplay of diverse factors presents a complex puzzle, difficult to resolve, and thus poses a substantial challenge. As instances of long COVID manifest by repeated infections of SARS-CoV-2 and genetic predisposition, a detailed understanding in this regard is needed. This endeavor is a comprehensive exploration and analysis of the cascading pathogenetic events driven by viral persistence and replication. Beyond its morbidity, long COVID, more disabling than fatal, exacts one of the most substantial tolls on public health in contemporary times, with the potential to cripple national economies. The paper introduces a unified theory of long COVID, detailing a novel pathophysiological framework that interlinks persistent SARS-CoV-2 infection, autoimmunity, and systemic vascular pathology. We posit a model where viral reservoirs, immune dysregulation, and genetic predispositions converge to perpetuate disease. It challenges prevailing hypotheses with new evidence, suggesting innovative diagnostic and therapeutic approaches. The paper aims to shift the paradigm in long COVID research by providing an integrative perspective that encapsulates the multifaceted nature of the condition. We explain the immunological mechanisms, hypercoagulability states, and viral reservoirs in the skull that feed NeuroCOVID in patients with long COVID. Also, this study hints toward a patient approach and how to prioritize treatment sequences in long COVID patients in hospitals and clinics. [ABSTRACT FROM AUTHOR]

Understanding the pathophysiology of long COVID is one of the most intriguing challenges confronting contemporary medicine. Despite observations recently made in the relevant molecular, cellular, and physiological domains, it is still difficult to say whether the post‐acute sequelae of COVID‐19 directly correspond to the consequences of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection. This work hypothesizes that neutrophils and neutrophil extracellular traps (NETs) production are at the interconnection of three positive feedback loops which are initiated in the acute phase of SARS‐CoV‐2 infection, and which involve inflammation, immunothrombosis, and autoimmunity. This phenomenon could be favored by the fact that SARS‐CoV‐2 may directly bind and penetrate neutrophils. The ensuing strong neutrophil stimulation leads to a progressive amplification of an exacerbated and uncontrolled NETs production, potentially persisting for months beyond the acute phase of infection. This continuous self‐stimulation of neutrophils leads, in turn, to systemic inflammation, micro‐thromboses, and the production of autoantibodies, whose significant consequences include the persistence of endothelial and multiorgan damage, and vascular complications. [ABSTRACT FROM AUTHOR]

Objectives: Hepatitis C virus (HCV) is one of the most global health problems with 2.5% prevalence worldwide. It seems that regulatory T (Treg) cells, which are able to modulate the host immune responses, play a substantial role in the immunopathogenesis of HCV infection. In this study, we evaluated the distribution of Treg cells in HCV-infected patients and its correlation with viral load and clinical manifestations. Methods: Peripheral blood mononuclear cells (PBMCs) were collected from 14 newly diagnosed HCV-infected patients and 23 age- and sex-matched healthy subjects, and the frequency of CD4+CD25+CD127−/low Treg cells was determined by flow cytometry. Results: Our results showed that the mean level of CD4+CD25+CD127−/low Treg cells in HCV-infected patients was significantly higher than that in healthy control subjects (8.2 ± 1.48% vs 5.4 ± 0.36%, p <.05). However, there was no statistical correlation between Treg cells frequency and viral load or clinical manifestations. Conclusion: A higher proportion of Treg cells in HCV-infected patients might indicate their critical role in viral persistence and candidate them as a new target of immunotherapy to improve antiviral immunity. [ABSTRACT FROM AUTHOR]

IntroductionHuman respiratory syncytial virus (hRSV) is a main cause of bronchiolitis in infants and its persistence has been described in immunocompromised subjects. However, limited evidence has been reported on the gene expression triggered by the hRSV and the effect of recombinant Taenia solium-derived calreticulin (rTsCRT).MethodsUsing a comprehensive microarray approach, we analyzed the transcriptome profile of a macrophage cell line that has supported hRSV persistence for over 150 passages. We compared the gene expression of persistently infected and non-infected macrophages. We also evaluated the effect of rTsCRT on hRSV-infected macrophage gene transcription, as well as on cytokine production and number of copies of the persistent hRSV genome.ResultsOur analysis showed that hRSV long-term virus infection significantly alters mRNA expression of antiviral, inflammatory, as well as arginine and lipid metabolism-associated genes, revealing a transcriptional signature that suggests a mixed M1/M2 phenotype. The resulting host-virus equilibrium allows for the regulation of viral replication, while evading the antiviral and proinflammatory responses. Interestingly, rTsCRT stimulus upregulated Tnfα, Il6 and Nos2 mRNA. We found increased levels of both proinflammatory cytokines and nitrite levels in the conditioned media of persistent macrophages treated with rTsCRT. This increase was associated with a significant reduction in viral genome copies.DiscussionhRSV persistently infected macrophages retain responsiveness to external stimuli and demonstrate that the profound changes induced by viral persistence are potentially reversible. Our observations contribute to the understanding of the mechanisms related to hRSV persistence in macrophages and have implications for the development of targeted therapies to eliminate persistent infections or reduce the negative effects related with chronic inflammatory diseases associated with hRSV infection.

Viral persistence is one of the main hypotheses explaining the presence of post-COVID symptoms. This systematic review investigated the presence of SARS-CoV-2 RNA in plasma, stool, urine, and nasal/oral swab samples in individuals with post-COVID symptomatology. MEDLINE, CINAHL, PubMed, EMBASE, Web of Science databases, as well as medRxiv/bioRxiv preprint servers were searched up to November 25th, 2023. Articles investigating the persistence of SARS-CoV-2 RNA in plasma, stool, urine or nasal/oral swab samples in patients with post-COVID symptoms were included. Methodological quality was assessed using the Newcastle–Ottawa Scale or Cochrane's Risk of Bias (Rob) tool. From 322 studies identified, six studies met all inclusion criteria. The sample included 678 COVID-19 survivors (52 % female, aged from 29 to 66 years). The methodological quality was moderate in 88 % of the studies (n=5/6). Three papers investigated the presence of SARS-CoV-2 RNA in plasma, three studies in nasal/oral swabs, two studies in stool samples, one in urine and one in saliva. The follow-up was shorter than two months (<60 days after) in 66 % of the studies (n=4/6). The prevalence of SARS-CoV-2 RNA ranged from 5 to 59 % in patients with post-COVID symptoms the first two months after infection, depending on the sample tested, however, SARS-CoV-2 RNA was also identified in COVID-19 survivors without post-COVID symptoms (one study). Available evidence can suggest the presence of persistent SARS-CoV-2 RNA in post-COVID patients in the short term, although the biases within the studies do not permit us to make firm assumptions. The association between post-COVID symptoms and SARS-CoV-2 RNA in the samples tested is also conflicting. The lack of comparative group without post-COVID symptoms limits the generalizability of viral persistence in post-COVID-19 condition. [ABSTRACT FROM AUTHOR]

The SARS‐CoV‐2 VIrus PERsistence (VIPER) study investigated the presence of long‐lasting SARS‐CoV‐2 RNA in plasma, stool, urine, and nasopharyngeal samples in COVID‐19 survivors. The presence of SARS‐CoV‐2 RNA reverse transcription polymerase chain reactions (RT‐PCR) were analyzed within plasma, stool, urine, and nasopharyngeal swab samples in COVID‐19 survivors with post‐COVID symptoms and a comparison group of COVID‐19 survivors without post‐COVID symptoms matched by age, sex, body mass index and vaccination status. Participants self‐reported the presence of any post‐COVID symptom (defined as a symptom that started no later than 3 months after the initial infection). Fifty‐seven (57.9% women, age: 51.1, standard deviation [SD]: 10.4 years) previously hospitalized COVID‐19 survivors with post‐COVID symptoms and 55 (56.4% women, age: 50.0, SD: 12.8 years) matched individuals who had a past SARS‐CoV‐2 infection without post‐COVID symptoms were evaluated 27 (SD 7.5) and 26 (SD 8.7) months after hospital discharge, respectively. The presence of SARS‐CoV‐2 RNA was identified in three nasopharyngeal samples of patients with post‐COVID symptoms (5.2%) but not in plasma, stool, or urine samples. Thus, SARS‐CoV‐2 RNA was not identified in any sample of survivors without post‐COVID symptoms. The most prevalent post‐COVID symptoms consisted of fatigue (93%), dyspnea, and pain (both, 87.7%). This study did not find SARS‐CoV‐2 RNA in plasma, stool, or urine samples, 2 years after the infection. A prevalence of 5.2% of SARS‐CoV‐2 RNA in nasopharyngeal samples, suggesting a potential active or recent reinfection, was found in patients with post‐COVID symptoms. These results do not support the association between SARS‐CoV‐2 RNA in plasma, stool, urine, or nasopharyngeal swab samples and post‐COVID symptomatology in the recruited population. [ABSTRACT FROM AUTHOR]

Combination antiretroviral therapy (ART) suppresses viral replication to undetectable levels, reduces mortality and morbidity, and improves the quality of life of people living with HIV (PWH). However, ART cannot cure HIV infection because it is unable to eliminate latently infected cells. HIV latency may be regulated by different HIV transcription mechanisms, such as blocks to initiation, elongation, and post-transcriptional processes. Several latency-reversing (LRA) and -promoting agents (LPA) have been investigated in clinical trials aiming to eliminate or reduce the HIV reservoir. However, none of these trials has shown a conclusive impact on the HIV reservoir. Here, we review the cellular and viral factors that regulate HIV-1 transcription, the potential pharmacological targets and genetic and epigenetic editing techniques that have been or might be evaluated to disrupt HIV-1 latency, the role of miRNA in post-transcriptional regulation of HIV-1, and the differences between the mechanisms regulating HIV-1 and HIV-2 expression. [ABSTRACT FROM AUTHOR]

Viral hepatitis is a major cause of liver illness worldwide. Despite advances in the understanding of these infections, the pathogenesis of hepatitis remains a complex process driven by intricate interactions between hepatitis viruses and host cells at the molecular level. This paper will examine in detail the dynamics of these host–pathogen interactions, highlighting the key mechanisms that regulate virus entry into the hepatocyte, their replication, evasion of immune responses, and induction of hepatocellular damage. The unique strategies employed by different hepatitis viruses, such as hepatitis B, C, D, and E viruses, to exploit metabolic and cell signaling pathways to their advantage will be discussed. At the same time, the innate and adaptive immune responses put in place by the host to counter viral infection will be analyzed. Special attention will be paid to genetic, epigenetic, and environmental factors that modulate individual susceptibility to different forms of viral hepatitis. In addition, this work will highlight the latest findings on the mechanisms of viral persistence leading to the chronic hepatitis state and the potential implications for the development of new therapeutic strategies. Fully understanding the complex host–pathogen interactions in viral hepatitis is crucial to identifying new therapeutic targets, developing more effective approaches for treatment, and shedding light on the mechanisms underlying progression to more advanced stages of liver damage.

A promising approach to help students safely return to in person learning is through the application of sentinel cards for accurate high resolution environmental monitoring of SARS-CoV-2 traces indoors. Because SARS-CoV-2 RNA can persist for up to a week on several indoor surface materials, there is a need for increased temporal resolution to determine whether consecutive surface positives arise from new infection events or continue to report past events. Cleaning sentinel cards after sampling would provide the needed resolution but might interfere with assay performance. We tested the effect of three cleaning solutions (BZK wipes, Wet Wipes, RNase Away) at three different viral loads: "high" (4 × 104 GE/mL), "medium" (1 × 104 GE/mL), and "low" (2.5 × 103 GE/mL). RNase Away, chosen as a positive control, was the most effective cleaning solution on all three viral loads. Wet Wipes were found to be more effective than BZK wipes in the medium viral load condition. The low viral load condition was easily reset with all three cleaning solutions. These findings will enable temporal SARS-CoV-2 monitoring in indoor environments where transmission risk of the virus is high and the need to avoid individual-level sampling for privacy or compliance reasons exists. IMPORTANCE Because SARS-CoV-2, the virus that causes COVID-19, persists on surfaces, testing swabs taken from surfaces is useful as a monitoring tool. This approach is especially valuable in school settings, where there are cost and privacy concerns that are eliminated by taking a single sample from a classroom. However, the virus persists for days to weeks on surface samples, so it is impossible to tell whether positive detection events on consecutive days are a persistent signal or new infectious cases and therefore whether the positive individuals have been successfully removed from the classroom. We compare several methods for cleaning "sentinel cards" to show that this approach can be used to identify new SARS-CoV-2 signals day to day. The results are important for determining how to monitor classrooms and other indoor environments for SARS-CoV-2 virus.

Heart disease is the leading cause of death worldwide. Myocarditis, or inflammation of the cardiac muscle, is estimated to cause up to 1.5 million cases annually, with viral infection being the most common disease culprit. Past studies have shown that Parvovirus B19 is routinely detected in endomyocardial biopsies. This virus has been linked to acute heart inflammation, which can cause cardiac muscle damage. However, because Parvovirus B19 can be found in the heart tissues in the absence of disease symptoms, it is unclear if the long-term presence of the virus contributes to, or initiates, heart disease. Here, we utilized a PCR-based detection assay to assess the presence of the B19V genome and its mRNA intermediates in human heart tissues. The analysis was carried out in three heart layers derived from one individual: epicardium, endocardium and myocardium. We showed the Parvovirus B19 genome presence variability in different heart layers. Similarly, viral transcriptional activity, assessed by the mRNA presence, was detected only in a few of the analyzed samples. Our results suggest that localized sites of Parvovirus B19 infection may exist within individual heart layers, which may have implication for the cardiac muscle inflammation. [ABSTRACT FROM AUTHOR]

Although cells of the myeloid lineages, including tissue macrophages and conventional dendritic cells, were rapidly recognized, in addition to CD4+ T lymphocytes, as target cells of HIV-1, their specific roles in the pathophysiology of infection were initially largely neglected. However, numerous studies performed over the past decade, both in vitro in cell culture systems and in vivo in monkey and humanized mouse animal models, led to growing evidence that macrophages play important direct and indirect roles as HIV-1 target cells and in pathogenesis. It has been recently proposed that macrophages are likely involved in all stages of HIV-1 pathogenesis, including virus transmission and dissemination, but above all, in viral persistence through the establishment, together with latently infected CD4+ T cells, of virus reservoirs in many host tissues, the major obstacle to virus eradication in people living with HIV. Infected macrophages are indeed found, very often as multinucleated giant cells expressing viral antigens, in almost all lymphoid and non-lymphoid tissues of HIV-1-infected patients, where they can probably persist for long period of time. In addition, macrophages also likely participate, directly as HIV-1 targets or indirectly as key regulators of innate immunity and inflammation, in the chronic inflammation and associated clinical disorders observed in people living with HIV, even in patients receiving effective antiretroviral therapy. The main objective of this review is therefore to summarize the recent findings, and also to revisit older data, regarding the critical functions of tissue macrophages in the pathophysiology of HIV-1 infection, both as major HIV-1-infected target cells likely found in almost all tissues, as well as regulators of innate immunity and inflammation during the different stages of HIV-1 pathogenesis. [ABSTRACT FROM AUTHOR]

In viral disease research, few diseases can compete with yellow fever for the volume of literature, historical significance, richness of the topics and the amount of strong interest among both scientists and laypersons. While the major foci of viral disease research shifted to other more pressing new diseases in recent decades, many critically important basic tasks still remain unfinished for yellow fever. Some of the examples include the mechanisms of transmission, the process leading to outbreak occurrence, environmental factors, dispersal, and viral persistence in nature. In this review, these subjects are analyzed in depth, based on information not only in old but in modern literatures, to fill in blanks and to update the current understanding on these topics. As a result, many valuable facts, ideas, and other types of information that complement the present knowledge were discovered. Very serious questions about the validity of the arbovirus concept and some research practices were also identified. The characteristics of YFV and its pattern of transmission that make this virus unique among viruses transmitted by Ae. aegypti were also explored. Another emphasis was identification of research questions. The discovery of a few historical surprises was an unexpected benefit. [ABSTRACT FROM AUTHOR]

Background: As the COVID-19 pandemic persists, infections continue to surge globally. Presently, the most effective strategies to curb the disease and prevent outbreaks involve fostering immunity, promptly identifying positive cases, and ensuring their timely isolation. Notably, there are instances where the SARS-CoV-2 virus remains infectious even after patients have completed their quarantine. Objective: Understanding viral persistence post-quarantine is crucial as it could account for localized infection outbreaks. Therefore, studying and documenting such instances is vital for shaping future public health policies. Design: This study delves into a unique case of SARS-CoV-2 persistence in a 60-year-old female healthcare worker with a medical history of hypertension and hypothyroidism. The research spans 55 days, marking the duration between her initial and subsequent diagnosis during Chile's first COVID-19 wave, with the analysis conducted using RT-qPCR. Results: Genomic sequencing-based phylogenetic analysis revealed that the SARS-CoV-2 detected in both Nasopharyngeal swab samples (NPSs) was consistent with the 20B clade of the Nextstrain classification, even after a 55-day interval. Conclusion: This research underscores the need for heightened vigilance concerning cases of viral persistence. Such instances, albeit rare, might be pivotal in understanding sporadic infection outbreaks that occur post-quarantine.

Background: Vaccination protects against severe COVID-19 manifestations. For those with post-COVID-19 conditions (PCC) or long COVID, the impact of COVID-19 vaccination on the evolution of symptoms, immune responses, and viral persistence is unclear. Methods: In this prospective observational cohort study, we evaluated the number of PCC symptoms, affected organ systems, and psychological well-being scores before and after patients with PCC received COVID-19 vaccination. We simultaneously evaluated biomarkers of systemic inflammation and levels of plasma cytokines/chemokines. We measured plasma and intracellular levels of SARS-CoV-2 antigens, and immunoreactivity to SARS-CoV-2 antigens in blood. Results: COVID-19 vaccination was associated with decreases in number of PCC symptoms (pre-vaccination: 6.56 ± 3.1 vs post-vaccination: 3.92 ± 4.02; P

Abstract Objective Identifying viral genomes in human heart tissues is critical for disease diagnosis and assessment of cardiovascular damage. Human heart tissue samples obtained during a biopsy procedure are routinely used to test for the presence of viruses, as guided by clinical manifestations and prognosis. Furthermore, heart tissue samples obtained post-mortem or during a cardiac transplant procedure serve as a valuable research tool, as they allow for an in-depth assessment of cardiac pathology that can aid in our understanding of molecular pathways associated with disease. Because viral nucleic acid constitutes only a small portion of each sample’s genetic material, appropriate methods are necessary for positive viral genome identification. Results Snap-frozen heart tissue samples obtained either post-mortem or during a cardiac transplant procedure were used to develop conditions for detection of Parvovirus B19. Briefly, total DNA was isolated from the heart tissue under varying conditions. A PCR-based assay with Parvovirus B19 specific primers was implemented to detect the presence of the viral genome, followed by Sanger Sequencing. The mechanical disruption of the heart tissue, as well as the cardiac tissue processing methods, had a significant effect on the DNA quality and the ability to detect the Parvovirus B19 genome.

Long COVID (post-acute sequelae of COVID-19—PASC) is a consequence of infection by SARS-CoV-2 that continues to disrupt the well-being of millions of affected individuals for many months beyond their first infection. While the exact mechanisms underlying PASC remain to be defined, hypotheses regarding the pathogenesis of long COVID are varied and include (but are not limited to) dysregulated local or systemic inflammatory responses, autoimmune mechanisms, viral-induced hormonal imbalances, skeletal muscle abnormalities, complement dysregulation, novel abzymes, and long-term persistence of virus and/or fragments of viral RNA or proteins. This review article is based on a comprehensive review of the wide range of symptoms most often observed in long COVID and an attempt to integrate that information into a plausible hypothesis for the pathogenesis of PASC. In particular, it is proposed that long-term dysregulation of the gut in response to viral persistence could lead to the myriad of symptoms observed in PASC.

Heart disease is the leading cause of death worldwide. Myocarditis, or inflammation of the cardiac muscle, is estimated to cause up to 1.5 million cases annually, with viral infection being the most common disease culprit. Past studies have shown that Parvovirus B19 is routinely detected in endomyocardial biopsies. This virus has been linked to acute heart inflammation, which can cause cardiac muscle damage. However, because Parvovirus B19 can be found in the heart tissues in the absence of disease symptoms, it is unclear if the long-term presence of the virus contributes to, or initiates, heart disease. Here, we utilized a PCR-based detection assay to assess the presence of the B19V genome and its mRNA intermediates in human heart tissues. The analysis was carried out in three heart layers derived from one individual: epicardium, endocardium and myocardium. We showed the Parvovirus B19 genome presence variability in different heart layers. Similarly, viral transcriptional activity, assessed by the mRNA presence, was detected only in a few of the analyzed samples. Our results suggest that localized sites of Parvovirus B19 infection may exist within individual heart layers, which may have implication for the cardiac muscle inflammation.

Ebola virus disease (EVD) has resulted in the death of over 15 000 people since its discovery in 1976. At least 1 incident of re-emergence of EVD has been associated with persistent male reproductive tract infection in a patient surviving EVD greater than 500 days prior. To date, animal models of Ebola virus (EBOV) infection have failed to fully characterize the pathogenesis of reproductive tract infection. Furthermore, no animal model of sexual transmission of EBOV exists. In this study, we describe a roadmap to modeling sexual transmission of EBOV using a mouse-adapted EBOV isolate in immunocompetent male mice and female Ifnar −/− mice. [ABSTRACT FROM AUTHOR]

Platelets are anucleate cytoplasmic cell fragments that circulate in the blood, where they are involved in regulating hemostasis. Beyond their normal physiologic role, platelets have emerged as versatile effectors of immune response. During an infection, cell surface receptors enable platelets to recognize viruses, resulting in their activation. Activated platelets release biologically active molecules that further trigger host immune responses to protect the body against infection. Their impact on the immune response is also associated with the recruitment of circulating leukocytes to the site of infection. They can also aggregate with leukocytes, including lymphocytes, monocytes, and neutrophils, to immobilize pathogens and prevent viral dissemination. Despite their host protective role, platelets have also been shown to be associated with various pathophysiological processes. In this review, we will summarize platelet and HIV interactions during infection. We will also highlight and discuss platelet and platelet-derived mediators, how they interact with immune cells, and the multifaceted responsibilities of platelets in HIV infection. Furthermore, we will give an overview of non-AIDS comorbidities linked to platelet dysfunction and the impact of antiretroviral therapy on platelet function. [ABSTRACT FROM AUTHOR]

• COVID-19 vaccination post-COVID-19 conditions (PCC) reduced the number of symptoms and increased well-being. • COVID-19 vaccination post-PCC down-regulated systemic markers of inflammation. • COVID-19 vaccination post-PCC did not abrogate the persistence of viral products. • A viral reservoir not cleared by one or two vaccine doses may persist. Vaccination protects against severe COVID-19 manifestations. For those with post-COVID-19 conditions (PCC) or long COVID, the impact of COVID-19 vaccination on the evolution of symptoms, immune responses, and viral persistence is unclear. In this prospective observational cohort study, we evaluated the number of PCC symptoms, affected organ systems, and psychological well-being scores before and after patients with PCC received COVID-19 vaccination. We simultaneously evaluated biomarkers of systemic inflammation and levels of plasma cytokines/chemokines. We measured plasma and intracellular levels of SARS-CoV-2 antigens, and immunoreactivity to SARS-CoV-2 antigens in blood. COVID-19 vaccination was associated with decreases in number of PCC symptoms (pre-vaccination: 6.56 ± 3.1 vs post-vaccination: 3.92 ± 4.02; P < 0.001) and affected organ systems (pre-vaccination: 3.19 ± 1.04 vs post-vaccination: 1.89 ± 1.12; P < 0.001), and increases in World Health Organization (WHO)-5 Well-Being Index Scores (pre-vaccination: 42.67 ± 22.76 vs post-vaccination: 56.15 ± 22.83; P < 0.001). Patients with PCC also had significantly decreased levels of several pro-inflammatory plasma cytokines/chemokines after COVID-19 vaccination including sCD40L, GRO-⍺, macrophage inflammatory protein (MIP)-1⍺, interleukin (IL)-12p40, G-colony stimulating factor (CSF), M-CSF, IL-1β, and stem cell factor (SCF). PCC participants presented a certain level of immunoreactivity toward SARS-CoV-2, that was boosted with vaccination. SARS-CoV-2 S1 antigen persisted in the blood of PCC participants, mostly in non-classical monocytes, regardless of participants receiving vaccination. Our study shows higher pro-inflammatory responses associated with PCC symptoms and brings forward a possible role for vaccination in mitigating PCC symptoms by decreasing systemic inflammation. We also observed persistence of viral products independent of vaccination that could be involved in perpetuating inflammation through non-classical monocytes. [ABSTRACT FROM AUTHOR]

We recently found that a new pathogenic chimeric simian-human immunodeficiency virus (SHIV) elicited heterologous human immunodeficiency virus type-1 (HIV-1) neutralizing antibodies (nAbs) in therapy-naïve young rhesus macaques (RMs) following neonatal SHIV infection. Moreover, a subset of the SHIV-infected young RMs spontaneously controlled viremia. Here we evaluated humoral and cellular immunity and plasma biomarkers associated with spontaneous viremia suppression in a new model of young SHIV-infected RMs that generated heterologous HIV-1 nAbs independent of viremia control to gain insights into pediatric immunity that may be harnessed by appropriate therapies in HIV-1-infected infants and children. We determined the levels of 31 plasma analytes (cytokines, chemokines, and growth factors) in SHIV-infected RMs over the course of infection and found that six analytes with chemoattractant or pro-inflammatory activities had significantly lower levels in plasma of RMs that controlled viremia compared to non-controllers. Single-cell transcriptomics of blood-derived immune cells demonstrated that RMs with viremia control had upregulated genes associated with immune activation and cytotoxic functions, whereas non-controllers had upregulated genes associated with immune cell exhaustion and dysfunction. In addition to CD8 T and natural killer cells, monocytes with upregulation of inhibitory genes previously reported only in cytotoxic cells constituted the immunologic environment associated with viremia suppression. These data implicated a complex immunologic milieu of viremia suppression that is not fully defined in pediatric subjects. Understanding immune cell subsets that may be harnessed to control viremia will provide insights into future designs of HIV-1 therapeutic strategies. [ABSTRACT FROM AUTHOR]

Chronic hepatitis B virus (HBV) infections affect over 250 million people worldwide, and over 800,000 are expected to die yearly from complications including cirrhosis and primary hepatocellular carcinoma. While clinically available nucleoside analog-based antiviral therapies inhibit virus production, they cannot cure infections due to the persistence of covalently closed circular (cccDNA) in the nuclei of infected hepatocytes. Hence, the goals of future curative antiviral therapies for chronic hepatitis B are to either eliminate or permanently silence transcription from cccDNA. Novel antiviral approaches building on a better understanding of the mechanisms underlying transcriptional regulation and the stability of HBV cccDNA will be necessary to accomplish such goals. To advance our understanding of cccDNA biology, we have employed a CRISPR/Cas9-based system to produce extrachromosomal circular (ec) DNA from plasmid DNA integrated into the host genome originally developed by Moller et al. [Nucleic Acid Research 46:(22) e131, 2018]. We modified the enhanced green fluorescent protein (EGFP) reporter system to include portions of the HBV genome encoding wild-type and inactive hepatitis B virus X (HBx) proteins on ecDNA to mimic cccDNA. We demonstrated that expression of EGFP is inhibited by the SMC5/6 complex, as is cccDNA, and that HBx expression can reverse transcriptional silencing of ecDNA. Moreover, we demonstrated that ecDNA is lost during cell division. The system described in this report permits investigations on ecDNA and enables large-scale screening of compound libraries for small molecules targeting host factors involved in ecDNA and, by inference, cccDNA transcription, maintenance, and loss during cell division. IMPORTANCE Hepatitis B virus cccDNA is the key target for the necessary development of antiviral therapies aimed at curing chronic hepatitis B. The CRISPR-based system to produce covalently closed circular (cccDNA)-like extrachromosomal DNAs described in this report enables large-scale screens of chemical libraries to identify drug candidates with the potential to permanently inactivate cccDNA. Moreover, this approach permits investigations on unresolved problems as described in this report concerning cccDNA biology including mechanisms of SMC5/6-dependent transcriptional silencing and the contributions of the SMC5/6 complex to cccDNA stability in resting and dividing hepatocytes. [ABSTRACT FROM AUTHOR]

Respiratory syncytial virus (RSV) causes annual epidemics of infections affecting the whole population. In vitro, it has been shown to infect and persist in human dendritic cells (DCs) for prolonged periods. Initially persistence is associated with low levels of replication before the virus becomes dormant. Reactivation of viral replication can be triggered many months later. Infection of DCs is likely to influence the host's ability to generate effective long-term memory responses. A well-established animal was utilized to confirm that RSV both infects and persists in pulmonary DCs in vivo. Mice were infected with a modified strain of RSV expressing red fluorescent protein (RSV-RFP) when replicating. Clinical symptoms of infection were monitored using weight change and inflammatory cell counts from bronchoalveolar lavage, which correlated with the RSV viral titer (quantitative polymerase chain reaction). Lung tissues were collected at 3, 5, 7, and 21 days postinfection (dpi) to assess leukocyte populations by flow cytometry. Clinical symptoms and RSV viral load peaked at 5 dpi. RSV-RFP was most prevalent in macrophages at 3 dpi and also observed in B cells and DCs. At 21 dpi, RSV-RFP remained evident in a subset of conventional DCs (CD103+CD11b+) even though both clinical symptoms and pulmonary inflammation had resolved. These results confirm that in this well-established mouse model, RSV persists in lung conventional DCs following resolution of the acute infection. Further work is required to explore whether the virus continues with low-level replication before becoming dormant in vivo, as has been described in vitro. [ABSTRACT FROM AUTHOR]

Arboviruses are an important group of pathogens that cause diseases of medical and veterinary concern worldwide. The interactions of these viruses with their host cells are complex, and frequently, the coexistence of two different viruses in the same cell results in the inhibition of replication in one of the viruses, which is a phenomenon called viral interference. This phenomenon can be exploited to develop antiviral strategies. Insect cell lines persistently infected with arboviruses are useful models with which to study viral interference. In this work, a model of C6/36-HT cells (from Aedes albopictus mosquitoes) persistently infected with Dengue virus, serotype 2, was used. Viral interference was evaluated via plaque and flow cytometry assays. The presence of heterotypic interference against the other serotypes of the same virus and homologous interference against yellow fever virus was determined; however, this cell line did not display heterologous viral interference against Sindbis virus. The mechanisms responsible for viral interference have not been fully elucidated, but small RNAs could be involved. However, the silencing of Ago3, a key protein in the genome-derived P-element-induced wimpy testis pathway, did not alter the viral interference process, suggesting that viral interference occurs independent of this pathway. [ABSTRACT FROM AUTHOR]

Combination antiretroviral therapy (ART) suppresses viral replication to undetectable levels, reduces mortality and morbidity, and improves the quality of life of people living with HIV (PWH). However, ART cannot cure HIV infection because it is unable to eliminate latently infected cells. HIV latency may be regulated by different HIV transcription mechanisms, such as blocks to initiation, elongation, and post-transcriptional processes. Several latency-reversing (LRA) and -promoting agents (LPA) have been investigated in clinical trials aiming to eliminate or reduce the HIV reservoir. However, none of these trials has shown a conclusive impact on the HIV reservoir. Here, we review the cellular and viral factors that regulate HIV-1 transcription, the potential pharmacological targets and genetic and epigenetic editing techniques that have been or might be evaluated to disrupt HIV-1 latency, the role of miRNA in post-transcriptional regulation of HIV-1, and the differences between the mechanisms regulating HIV-1 and HIV-2 expression.

Background Late-relapsing hepatitis after yellow fever (LHep-YF) during the convalescent phase of the disease has been described during recent yellow fever (YF) outbreaks in Brazil. LHep-YF is marked by a rebound in liver enzymes and nonspecific clinical manifestations around 46–60 days after YF symptom onset. Methods Here we have characterized the clinical course and risk factors for LHep-YF using data from a representative cohort of patients who survived YF in Brazil, 2017–2018. A total of 221 YF-positive patients were discharged from the infectious disease reference hospital in Minas Gerais and were followed up at 30, 45, and 60 days post–symptom onset. Results From 46 to 60 days post–symptom onset, 16% of YF patients (n = 36/221) exhibited a rebound of aminotransferases (aspartate aminotransferase or alanine aminotransferase >500 IU/L), alkaline phosphatase, and total bilirubin levels. Other etiologies of liver inflammation such as infectious hepatitis, autoimmune hepatitis, and metabolic liver disease were ruled out. Jaundice, fatigue, headache, and low platelet levels were associated with LHep-YF. Demographic factors, clinical manifestations, laboratory tests, ultrasound findings, and viral load during the acute phase of YF were not associated with the occurrence of LHep-YF. Conclusions These findings provide new data on the clinical course of Late-relapsing hepatitis during the convalescent phase of YF and highlight the need for extended patient follow-up after acute YF. [ABSTRACT FROM AUTHOR]

For over three years, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in children and adolescents has generated repercussions, especially a few weeks after infection, for symptomatic patients who tested positive, for asymptomatic ones, or even just the contacts of an infected person, and evolved from severe forms such as multisystem inflammatory syndrome in children (MIS-C) to multifarious clinical manifestations in long COVID (LC). Referred to under the umbrella term LC, the onset of persistent and highly heterogeneous symptoms such as fatigue, post-exertion malaise, cognitive dysfunction, and others have a major impact on the child's daily quality of life for months. The first aim of this review was to highlight the circumstances of the pathophysiological changes produced by COVID-19 in children and to better understand the hyperinflammation in COVID-19 and how MIS-C, as a life-threatening condition, could have been avoided in some patients. Another goal was to better identify the interplay between infection, dysbiosis, and inflammation at a molecular and cellular level, to better guide scientists, physicians, and pediatricians to advance new lines of medical action to avoid the post-acute sequelae of SARS-CoV-2 infection. The third objective was to identify symptoms and their connection to molecular pathways to recognize LC more easily. The fourth purpose was to connect the triggering factors of LC with related sequelae following acute SARS-CoV-2 injuries to systems and organs, the persistence of the virus, and some of its components in hidden reservoirs, including the gut and the central nervous system. The reactivation of other latent infectious agents in the host's immune environments, the interaction of this virus with the microbiome, immune hyperactivation, and autoimmunity generated by molecular mimicry between viral agents and host proteins, could initiate a targeted and individualized management. New high-tech solutions, molecules, probiotics, and others should be discovered to innovatively solve the interplay between RNA persistent viruses, microbiota, and our immune system. [ABSTRACT FROM AUTHOR]

Background: At what rate does the RNA of SARS CoV-2 shed from cadavers? Although, there have been numerous studies which have demonstrated the persistence of the virus on dead bodies, there is a lack of conclusive evidence regarding the variation of viral RNA content in cadavers. This has led to a knowledge gap regarding the safe handling/management of COVID-19 decedents, posing a barrier in forensic investigations. Methods: In this study, we report the presence of RNA of SARS CoV-2 by real time RT-PCR, in nasopharyngeal swabs collected after death from two groups of bodies – one who died due to COVID-19 and the other who died due to other diagnoses. A prospective study on 199 corpses, who had tested positive for COVID-19 ante-mortem, was conducted at a tertiary care center. RNA testing was conducted at different time intervals (T1-T5). Results: 112(56.3%) died primarily due to COVID-19 and 87(43.7%) died due to other diagnoses. 144(72.4%) were male and 55(27.6%) were female. A total of 115 (57.8%) tested positive for COVID-19 after death at different time points. The mean age was 50.7 ± 18.9 years and the length of hospitalization ranged from 1 to 50 days with a mean of 9.2 ± 7.6 days. Realtime RT-PCR positivity of SARS CoV-2 RNA decreases with time. Conclusion: We observed that real time RT-PCR positivity, indicating viral RNA detection, decreases with time. Therefore, it is advisable to follow appropriate COVID-19 precautions to carry out scientific studies, medico-legal investigations and mortuary services on suspected/confirmed COVID-19 corpses.

Hepatitis E virus (HEV) can infect a wide range of domestic and wild animals, and the identification of new host species is reported successively worldwide. Nevertheless, its zoonotic potential and natural transmission, especially in wildlife remains unclear, primarily due to the discrete nature of HEV infections. Since the red fox (Vulpus vulpus) is the most widespread carnivore worldwide, and has been recognized as a potential HEV reservoir, its role as a potent host species is of increasing interest. Another wild canine species, the jackal （Canis aureus moreoticus）, is becoming more important within the same habitat as that of the red fox since its number and geographical distribution have been rapidly growing. Therefore, we have chosen these wild species to determine their potential role in the epidemiology and persistence of HEV in the wilderness. The main reason for this is the finding of HEV and a rather high HEV seroprevalence in wild boars sharing the same ecological niche as the wild canine species, as well as the risk of the spread of HEV through red foxes into the outskirts of cities, where possible indirect and even direct contact with people are not excluded. Therefore, our study aimed to investigate the possibility of natural HEV infection of free-living wild canines, by testing samples for the presence of HEV RNA and anti-HEV antibodies to gain better epidemiological knowledge of the disease. For this purpose, 692 red fox and 171 jackal muscle extracts and feces samples were tested. Neither HEV RNA nor anti-HEV antibodies were detected. Although HEV circulation was not detected in the tested samples, to our knowledge, these are the first results that include jackals as a growing and important omnivore wildlife species for the presence of HEV infection in Europe. [ABSTRACT FROM AUTHOR]

Although cells of the myeloid lineages, including tissue macrophages and conventional dendritic cells, were rapidly recognized, in addition to CD4+ T lymphocytes, as target cells of HIV-1, their specific roles in the pathophysiology of infection were initially largely neglected. However, numerous studies performed over the past decade, both in vitro in cell culture systems and in vivo in monkey and humanized mouse animal models, led to growing evidence that macrophages play important direct and indirect roles as HIV-1 target cells and in pathogenesis. It has been recently proposed that macrophages are likely involved in all stages of HIV-1 pathogenesis, including virus transmission and dissemination, but above all, in viral persistence through the establishment, together with latently infected CD4+ T cells, of virus reservoirs in many host tissues, the major obstacle to virus eradication in people living with HIV. Infected macrophages are indeed found, very often as multinucleated giant cells expressing viral antigens, in almost all lymphoid and non-lymphoid tissues of HIV-1-infected patients, where they can probably persist for long period of time. In addition, macrophages also likely participate, directly as HIV-1 targets or indirectly as key regulators of innate immunity and inflammation, in the chronic inflammation and associated clinical disorders observed in people living with HIV, even in patients receiving effective antiretroviral therapy. The main objective of this review is therefore to summarize the recent findings, and also to revisit older data, regarding the critical functions of tissue macrophages in the pathophysiology of HIV-1 infection, both as major HIV-1-infected target cells likely found in almost all tissues, as well as regulators of innate immunity and inflammation during the different stages of HIV-1 pathogenesis.

The COVID-19 global pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has infected hundreds of millions of individuals. Following COVID-19 infection, a subset can develop a wide range of chronic symptoms affecting diverse organ systems referred to as post-acute sequelae of SARS-CoV-2 infection (PASC), also known as long COVID. A National Institutes of Health-sponsored initiative, RECOVER: Researching COVID to Enhance Recovery, has sought to understand the basis of long COVID in a large cohort. Given the range of symptoms that occur in long COVID, the mechanisms that may underlie these diverse symptoms may also be diverse. In this review, we focus on the emerging literature supporting the role(s) that viral persistence or reactivation of viruses may play in PASC. Persistence of SARS-CoV-2 RNA or antigens is reported in some organs, yet the mechanism by which they do so and how they may be associated with pathogenic immune responses is unclear. Understanding the mechanisms of persistence of RNA, antigen or other reactivated viruses and how they may relate to specific inflammatory responses that drive symptoms of PASC may provide a rationale for treatment.

Many herbivorous insects die of pathogen infections, though the role of plant traits in promoting the persistence of these pathogens as an indirect interaction is poorly understood. We tested whether winter leaf retention of bush lupines (Lupinus arboreus) promotes the persistence of a nucleopolyhedroviruses, thereby increasing the infection risk of caterpillars (Arctia virginalis) feeding on the foliage during spring. We also investigated whether winter leaf retention reduces viral exposure of younger caterpillars that live on the ground, as leaf retention prevents contaminated leaves from reaching the ground. We surveyed winter leaf retention of 248 lupine bush canopies across twelve sites and examined how it related to caterpillar infection risk, herbivory, and inflorescence density. We also manipulated the amount of lupine litter available to young caterpillars in a feeding experiment to emulate litterfall exposure in the field. Greater retention of contaminated leaves from the previous season increased infection rates of caterpillars in early spring. Higher infection rates reduced herbivory and increased plant inflorescence density by summer. Young caterpillars exposed to less litterfall were more likely to starve to death but less likely to die from infection, further suggesting foliage mediated exposure to viruses. We speculate that longer leaf life span may be an unrecognized trait that indirectly mediates top-down control of herbivores by facilitating epizootics. [ABSTRACT FROM AUTHOR]

The establishment of persistent dengue virus infection within the cells of the mosquito vector is an essential requirement for viral transmission to a new human host. The mechanisms involved in the establishment and maintenance of persistent infection are not well understood, but it has been suggested that both viral and cellular factors might play an important role. In the present work, we evaluated differential gene expression in Aedes albopictus cells acutely (C6/36-HT) and persistently infected (C6-L) with Dengue virus 2 by cDNA-AFLP. We observed that importin β3 was upregulated in noninfected cells compared with C6-L cells. Using RT-qPCR and plaque assays, we observed that Dengue virus levels in C6-L cells essentially do not vary over time, and peak viral titers in acutely infected cells are observed at 72 and 120 h postinfection. The expression level of importin β3 was higher in acutely infected cells than in persistently infected cells; this correlates with higher levels of NS5 in the nucleus of the cell. The differential pattern of importin β3 expression between acute and persistent infection with Dengue virus 2 could be a mechanism to maintain viral infection over time, reducing the antiviral response of the cell and the viral replicative rate. [ABSTRACT FROM AUTHOR]

Respiratory RNA viruses are a major cause of acute lower respiratory tract infections and contribute substantially to hospitalization among infants, elderly, and immunocompromised. Complete viral clearance from acute infections is not always achieved, leading to persistence. Certain chronic respiratory diseases like asthma and chronic obstructive pulmonary disease have been associated with persistent infection by human respiratory syncytial virus and human rhinovirus, but it is still not clear whether RNA viruses really establish long-term infections as it has been recognized for DNA viruses as human bocavirus and adenoviruses. Herein, we summarize evidence of RNA virus persistence in the human respiratory tract, as well as in some animal models, to highlight how long-term infections might be related to development and/or maintenance of chronic respiratory symptoms. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancer cells amplify in an uncontrolled fashion. The resulting tumor and metastases need to ensure their survival in the body. To achieve this, cancer cells display increased nutritional needs and an altered metabolism. These metabolic changes start to be targeted for therapeutic interventions in the context of a number of different cancers. Similar to cancer, cells infected with viruses that cause cancer, so-called "oncoviruses", have altered nutritional needs to support the amplification and spread of new progeny viruses and to ensure the survival of infected cells in the host. Here, we give an update on the similarities between the metabolic alterations observed in many types of cancers and those induced by oncogenic viruses. Furthermore, we discuss the antiviral activities of metabolic inhibitors used for the treatment of cancer. Viruses play an important role in cancer development as about 12% of cancer types are linked to viral infections. Viruses that induce cellular transformation are known as oncoviruses. Although the mechanisms of viral oncogenesis differ between viruses, all oncogenic viruses share the ability to establish persistent chronic infections with no obvious symptoms for years. During these prolonged infections, oncogenic viruses manipulate cell signaling pathways that control cell cycle progression, apoptosis, inflammation, and metabolism. Importantly, it seems that most oncoviruses depend on these changes for their persistence and amplification. Metabolic changes induced by oncoviruses share many common features with cancer metabolism. Indeed, viruses, like proliferating cancer cells, require increased biosynthetic precursors for virion production, need to balance cellular redox homeostasis, and need to ensure host cell survival in a given tissue microenvironment. Thus, like for cancer cells, viral replication and persistence of infected cells frequently depend on metabolic changes. Here, we draw parallels between metabolic changes observed in cancers or induced by oncoviruses, with a focus on pathways involved in the regulation of glucose, lipid, and amino acids. We describe whether and how oncoviruses depend on metabolic changes, with the perspective of targeting them for antiviral and onco-therapeutic approaches in the context of viral infections. [ABSTRACT FROM AUTHOR]

At what rate does the RNA of SARS CoV-2 shed from cadavers? Although, there have been numerous studies which have demonstrated the persistence of the virus on dead bodies, there is a lack of conclusive evidence regarding the variation of viral RNA content in cadavers. This has led to a knowledge gap regarding the safe handling/management of COVID-19 decedents, posing a barrier in forensic investigations. In this study, we report the presence of RNA of SARS CoV-2 by real time RT-PCR, in nasopharyngeal swabs collected after death from two groups of bodies – one who died due to COVID-19 and the other who died due to other diagnoses. A prospective study on 199 corpses, who had tested positive for COVID-19 ante-mortem, was conducted at a tertiary care center. RNA testing was conducted at different time intervals (T1-T5). 112(56.3%) died primarily due to COVID-19 and 87(43.7%) died due to other diagnoses. 144(72.4%) were male and 55(27.6%) were female. A total of 115 (57.8%) tested positive for COVID-19 after death at different time points. The mean age was 50.7 ± 18.9 years and the length of hospitalization ranged from 1 to 50 days with a mean of 9.2 ± 7.6 days. Realtime RT-PCR positivity of SARS CoV-2 RNA decreases with time. We observed that real time RT-PCR positivity, indicating viral RNA detection, decreases with time. Therefore, it is advisable to follow appropriate COVID-19 precautions to carry out scientific studies, medico-legal investigations and mortuary services on suspected/confirmed COVID-19 corpses. • Lack of conclusive evidence on the persistence of SARS CoV-2 virus on corpses. • Realtime RT-PCR positivity of SARS CoV-2 RNA decreases with time. • Safe handling and management of confirmed/suspected COVID-19 positive cadavers. [ABSTRACT FROM AUTHOR]

We report detecting infectious Toscana virus in the seminal fluid of a 25-year-old man from Italy returning from Elba Island. The presence of infectious virus in human semen adds Toscana virus to the long list of viruses detected in this genital fluid and indicates a potential for sexual transmission.

Climate change is intensifying extreme weather events in coastal areas, leading to more frequent discharge of untreated wastewater containing human viruses into coastal waters. This poses a health risk, especially during heatwaves when bathing activity increases. A study examined the survival and viability of seven common wastewater viruses in seawater at different temperatures. Viral genomes were quantified using direct qPCR, whilst viability was assessed using Capsid Integrity qPCR. Results showed that T90 values from direct qPCR were much higher than those from CI-qPCR, suggesting that risk mitigation should be based on viral integrity tests. All viruses remained potentially viable for at least 72 h in environmental seawater and longer in sterile artificial seawater, highlighting the importance of biotic processes in viral inactivation. Viral persistence decreased with increasing temperature. Whilst heatwaves may partially reduce risks from human viral pathogens in coastal waters, they do not eliminate them entirely. [Display omitted] • Viruses pose a human health risk in coastal water many days after sewage discharge. • Viral RNA quantified using qPCR overestimates viral decay times. • Combining molecular and viability assays is essential for estimating viral public health risk. • Viral capsids remained intact in seawater for at least 72 h, with some persisting over 2 weeks. [ABSTRACT FROM AUTHOR]

Platelets are anucleate cytoplasmic cell fragments that circulate in the blood, where they are involved in regulating hemostasis. Beyond their normal physiologic role, platelets have emerged as versatile effectors of immune response. During an infection, cell surface receptors enable platelets to recognize viruses, resulting in their activation. Activated platelets release biologically active molecules that further trigger host immune responses to protect the body against infection. Their impact on the immune response is also associated with the recruitment of circulating leukocytes to the site of infection. They can also aggregate with leukocytes, including lymphocytes, monocytes, and neutrophils, to immobilize pathogens and prevent viral dissemination. Despite their host protective role, platelets have also been shown to be associated with various pathophysiological processes. In this review, we will summarize platelet and HIV interactions during infection. We will also highlight and discuss platelet and platelet-derived mediators, how they interact with immune cells, and the multifaceted responsibilities of platelets in HIV infection. Furthermore, we will give an overview of non-AIDS comorbidities linked to platelet dysfunction and the impact of antiretroviral therapy on platelet function.

Arboviruses are an important group of pathogens that cause diseases of medical and veterinary concern worldwide. The interactions of these viruses with their host cells are complex, and frequently, the coexistence of two different viruses in the same cell results in the inhibition of replication in one of the viruses, which is a phenomenon called viral interference. This phenomenon can be exploited to develop antiviral strategies. Insect cell lines persistently infected with arboviruses are useful models with which to study viral interference. In this work, a model of C6/36-HT cells (from Aedes albopictus mosquitoes) persistently infected with Dengue virus, serotype 2, was used. Viral interference was evaluated via plaque and flow cytometry assays. The presence of heterotypic interference against the other serotypes of the same virus and homologous interference against yellow fever virus was determined; however, this cell line did not display heterologous viral interference against Sindbis virus. The mechanisms responsible for viral interference have not been fully elucidated, but small RNAs could be involved. However, the silencing of Ago3, a key protein in the genome-derived P-element-induced wimpy testis pathway, did not alter the viral interference process, suggesting that viral interference occurs independent of this pathway.

The prevalence of low virulence classical swine fever virus (CSFV) strains makes viral eradication difficult in endemic countries. However, the determinants for natural CSFV attenuation and persistence in the field remain unidentified. The aim of the present study was to assess the role of the RNase activity of CSFV Erns in pathogenesis, immune response, persistent infection, and viral transmission in pigs. To this end, a functional cDNA clone pPdR-H30K-36U with an Erns lacking RNase activity was constructed based on the low virulence CSFV field isolate Pinar de Rio (PdR). Eighteen 5-day-old piglets were infected with vPdR-H30K-36U. Nine piglets were introduced as contacts. The vPdR-H30K-36U virus was attenuated in piglets compared to the parental vPdR-36U. Only RNA traces were detected in sera and body secretions and no virus was isolated from tonsils, showing that RNase inactivation may reduce CSFV persistence and transmissibility. The vPdR-H30K-36U mutant strongly activated the interferon-α (IFN-α) production in plasmacytoid dendritic cells, while in vivo, the IFN-α response was variable, from moderate to undetectable depending on the animal. This suggests a role of the CSFV Erns RNase activity in the regulation of innate immune responses. Infection with vPdR-H30K-36U resulted in higher antibody levels against the E2 and Erns glycoproteins and in enhanced neutralizing antibody responses when compared with vPdR-36U. These results pave the way toward a better understanding of viral attenuation mechanisms of CSFV in pigs. In addition, they provide novel insights relevant for the development of DIVA vaccines in combination with diagnostic assays for efficient CSF control.

A young man with X-linked severe combined immunodeficiency developed a persistent vaccine-derived rubella virus (VDRV) infection, with the emergence of cutaneous granulomas more than fifteen years after receipt of two doses of measles-mumps-rubella (MMR) vaccine. Following nasopharyngeal swab (NP) collection, VDRV was detected by real-time polymerase chain reaction (RT-qPCR) and sequencing, and live, replication-competent VDRV was isolated in cell culture. To assess duration and intensity of viral shedding, sequential respiratory samples, one cerebrospinal fluid sample, and two urine samples were collected over 15 months, and VDRV RNA was detected in all samples by RT-qPCR. Live VDRV was cultured from nine of the eleven respiratory specimens and from one urine specimen. To our knowledge, this was the first reported instance of VDRV cultured from respiratory specimens or from urine. To assess potential transmission to close contacts, NP specimens and sera were collected from all household contacts, all of whom were immunocompetent and previously vaccinated with MMR. VDRV RNA was not detected in any NP swabs from the contacts, nor did serologic investigations suggest VDRV transmission to any contacts. This report highlights the need to understand the prevalence and duration of VDRV shedding in granuloma patients and to estimate the risk of VDRV transmission to immune and non-immune contacts.