22 results on '"Tianyu Gan"'
Search Results
2. Isolation of a recombinant simian adenovirus encoding the human adenovirus G52 hexon suggests a simian origin for human adenovirus G52.
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Pinski, Amanda N., Tianyu Gan, Shih-Ching Lin, Droit, Lindsay, Diamond, Michael, Barouch, Dan H., and Wang, David
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ADENOVIRUSES , *HUMAN origins , *WHOLE genome sequencing , *RHESUS monkeys , *DNA viruses , *HUMAN adenoviruses - Abstract
Human adenoviruses (HAdVs) are causative agents of morbidity and mortality throughout the world. These double-stranded DNA viruses are phylogenetically classified into seven different species (A-G). HAdV-G52, originally isolated in 2008 from a patient presenting with gastroenteritis, is the sole human-derived member of species G. Phylogenetic analysis previously suggested that HAdV-G52 may have a simian origin, indicating a potential zoonotic spillover into humans. However, evidence of HAdV-G52 in either human or simian populations has not been reported since. Here, we describe the isolation and in vitro characterization of rhesus (rh)AdV-69, a novel simian AdV with clear evidence of recombination with HAdV-G52, from the stool of a rhesus macaque. Specifically, the rhAdV-69 hexon capsid protein is 100% identical to that of HAdV-G52, whereas the remainder of the genome is most similar to rhAdV-55, sharing 95.36% nucleic acid identity. A second recombination event with an unknown adenovirus (AdV) is evident at the short fiber gene. From the same sample, we also isolated a second, highly related recombinant AdV (rhAdV-68) that harbors a distinct hexon gene but nearly identical backbone compared to rhAdV-69. In vitro, rhAdV-68 and rhAdV-69 demonstrate comparable growth kinetics and tropisms in human cell lines, nonhuman cell lines, and human enteroids. Furthermore, we show that coinfection of highly related AdVs is not unique to this sample since we also isolated coinfecting rhAdVs from two additional rhesus macaque stool samples. Our data collectively contribute to elucidating the origins of HAdV-G52 and provide insights into the frequency of coinfections and subsequent recombination in AdV evolution. IMPORTANCE Understanding the host origins of adenoviruses (AdVs) is critical for public health as transmission of viruses from animals to humans can lead to emergent viruses. Recombination between animal and human AdVs can also produce emergent viruses. HAdV-G52 is the only human-derived member of the HAdV G species. It has been suggested that HAdV-G52 has a simian origin. Here, we isolated from a rhesus macaque, a novel rhAdV, rhAdV-69, that encodes a hexon protein that is 100% identical to that of HAdV-G52. This observation suggests that HAdV-G52 may indeed have a simian origin. We also isolated a highly related rhAdV, differing only in the hexon gene, from the same rhesus macaque stool sample as rhAdV-69, illustrating the potential for co-infection of closely related AdVs and recombination at the hexon gene. Furthermore, our study highlights the critical role of whole-genome sequencing in understanding AdV evolution and monitoring the emergence of pathogenic AdVs. [ABSTRACT FROM AUTHOR]
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- 2024
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3. Isolation of a rhesus calicivirus that can replicate in human cells
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Tianyu Gan, Lindsay Droit, Susan Vernon, Dan H. Barouch, and David Wang
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Virology - Published
- 2023
4. Picobirnaviruses encode proteins that are functional bacterial lysins.
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Tianyu Gan and Wang, David
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LYSINS , *DOUBLE-stranded RNA , *GESTATIONAL diabetes , *RNA viruses , *GRAFT versus host disease - Abstract
Picobirnaviruses (PBVs) are double-stranded RNA viruses frequently detected in human and animal enteric viromes. Associations of PBVs with enteric graft-versus-host disease and type I diabetes during pregnancy have been established. Since their discovery in 1988, PBVs have been generally assumed to be animal-infecting viruses despite the lack of culture system, animal model, or detection in animal cells or tissues. Recent studies have proposed that bacteria or fungi could be the hosts of PBVs based on genomic analysis. Here, we functionally demonstrate that multiple PBVs of different genome organizations encode bacterial lysins that lyse Escherichia coli. Such genes are typically encoded only by bacteriophages supporting the model that PBVs infect bacterial hosts. Recognition of PBVs as RNA phages in the human gut would completely shift models of how PBVs could impact human health. In addition, expanding the RNA phage world beyond the two recognized clades to three clades has implications for our understanding of the evolution of RNA viruses. [ABSTRACT FROM AUTHOR]
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- 2023
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5. The highly conserved stem-loop II motif is dispensable for SARS-CoV-2
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Hongbing Jiang, Astha Joshi, Tianyu Gan, Andrew B. Janowski, Chika Fujii, Traci L. Bricker, Tamarand L. Darling, Houda H. Harastani, Kuljeet Seehra, Hongwei Chen, Stephen Tahan, Ana Jung, Binita Febles, Joshua A. Blatter, Scott A. Handley, Bijal A. Parikh, David Wang, and Adrianus C. M. Boon
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Virology ,Insect Science ,Immunology ,Microbiology ,Article - Abstract
The stem-loop II motif (s2m) is a RNA structural element that is found in the 3’ untranslated region (UTR) of many RNA viruses including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Though the motif was discovered over twenty-five years ago, its functional significance is unknown. In order to understand the importance of s2m, we created viruses with deletions or mutations of the s2m by reverse genetics and also evaluated a clinical isolate harboring a unique s2m deletion. Deletion or mutation of the s2m had no effect on growthin vitro, or growth and viral fitness in Syrian hamstersin vivo. We also compared the secondary structure of the 3’ UTR of wild type and s2m deletion viruses using SHAPE-MaP and DMS-MaPseq. These experiments demonstrate that the s2m forms an independent structure and that its deletion does not alter the overall remaining 3’UTR RNA structure. Together, these findings suggest that s2m is dispensable for SARS-CoV-2.IMPORTANCERNA viruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) contain functional structures to support virus replication, translation and evasion of the host antiviral immune response. The 3’ untranslated region of early isolates of SARS-CoV-2 contained a stem-loop II motif (s2m), which is a RNA structural element that is found in many RNA viruses. This motif was discovered over twenty-five years ago, but its functional significance is unknown. We created SARS-CoV-2 with deletions or mutations of the s2m and determined the effect of these changes on viral growth in tissue culture and in rodent models of infection. Deletion or mutation of the s2m element had no effect on growthin vitro, or growth and viral fitness in Syrian hamstersin vivo. We also observed no impact of the deletion on other known RNA structures in the same region of the genome. These experiments demonstrate that the s2m is dispensable for SARS-CoV-2.
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- 2023
6. Novel quinolone derivatives targeting human dihydroorotate dehydrogenase suppress Ebola virus infection in vitro
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Yiqing Yang, Qiang Ding, Jin Zhong, Qianqian Li, Yue Wu, Youchun Wang, Weijin Huang, Tianyu Gan, Hongying Gao, Fei Deng, Rong Zhang, Yu Rao, Jianhui Nie, Mingli Gong, and Yi Huang
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medicine.drug_class ,Dihydroorotate Dehydrogenase ,Quinolones ,medicine.disease_cause ,Virus Replication ,Antiviral Agents ,Cell Line ,Inhibitory Concentration 50 ,Virology ,medicine ,Humans ,Pharmacology ,chemistry.chemical_classification ,Ebola virus ,Alanine ,biology ,RNA virus ,Hemorrhagic Fever, Ebola ,Quinolone ,biology.organism_classification ,Ebolavirus ,In vitro ,Adenosine Monophosphate ,De novo synthesis ,Africa, Western ,Enzyme ,chemistry ,Pyrimidine metabolism ,Dihydroorotate dehydrogenase - Abstract
Ebola virus (EBOV) has emerged as a significant public health concern since the 2013–2016 outbreak in West Africa. Currently, no effective antiviral treatments have been approved for clinical use. Compound 1 RYL-634 is a quinolone-derived compound that can inhibit dihydroorotate dehydrogenase, a rate-limiting enzyme in the de novo pyrimidine synthesis pathway and it exhibited antiviral activity against multiple RNA virus infection. In this study, we evaluated the efficacy of a panel of newly developed compounds based on RYL-634 against EBOV infection. Our data showed that RYL-634 as well as its derivatives are effective against EBOV transcription- and replication-competent virus-like particle (trVLP) infection and authentic EBOV infection in vitro at low nanomolar IC50 values and relatively high CC50. Of note, the new derivative RYL-687 had the lowest IC50 at approximately 7 nM and was almost 6 times more potent than remdesivir (GS-5734). Exogenous addition of different metabolites in the pyrimidine de novo synthesis pathway confirmed DHODH as the target of RYL-687. These data provide evidence that such quinolone-derived compounds are promising therapeutic candidates against EBOV infection.
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- 2021
7. Development of a New Reverse Genetics System for Ebola Virus
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Ziyue Ma, Tianyu Gan, Shuqi Xiao, Yi Huang, Xiaoyou Hu, Huimin Yan, Yimin Tong, Dihan Zhou, and Jin Zhong
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0301 basic medicine ,filovirus ,Viral protein ,viruses ,030106 microbiology ,Population ,negative-stranded RNA virus ,Genome, Viral ,Biology ,medicine.disease_cause ,Microbiology ,Virus ,Cell Line ,03 medical and health sciences ,Ebola virus ,reverse genetics ,VP40 ,Virology ,medicine ,education ,Molecular Biology ,education.field_of_study ,virus diseases ,RNA virus ,biology.organism_classification ,Ebolavirus ,QR1-502 ,Nucleoprotein ,030104 developmental biology ,Viral replication ,RNA, Viral ,Research Article - Abstract
Ebola virus is among the most dangerous viral pathogens, with a case fatality rate of up to 90%. Since 2013, the two largest and most complex Ebola outbreaks in West Africa have revealed the lack of investigation on this notorious virus., Ebola virus (EBOV) is a highly pathogenic negative-stranded RNA virus that has caused several deadly endemics in the past decades. EBOV reverse genetics systems are available for studying live viruses under biosafety level 4 (BSL-4) or subviral particles under BSL-2 conditions. However, these systems all require cotransfection of multiple plasmids expressing viral genome and viral proteins essential for EBOV replication, which is technically challenging and unable to naturally mimic virus propagation using the subviral particle. Here, we established a new EBOV reverse genetics system only requiring transfection of a single viral RNA genome into an engineered cell line that stably expresses viral nucleoprotein (NP), viral protein 35 (VP35), VP30, and large (L) proteins and has been fine-tuned for its superior permissiveness for EBOV replication. Using this system, subviral particles expressing viral VP40, glycoprotein (GP), and VP24 could be produced and continuously propagated and eventually infect the entire cell population. We demonstrated the authentic response of the subviral system to antivirals and uncovered that the VP35 amount is critical for optimal virus replication. Furthermore, we showed that fully infectious virions can be efficiently rescued by delivering the full-length EBOV genome into the same supporting cell, and the efficiency is not affected by genome polarity or virus variant specificity. In summary, our work provides a new tool for studying EBOV under different biosafety levels. IMPORTANCE Ebola virus is among the most dangerous viral pathogens, with a case fatality rate of up to 90%. Since 2013, the two largest and most complex Ebola outbreaks in Africa have revealed the lack of investigation on this notorious virus. A reverse genetics system is an important tool for studying viruses by producing mutant viruses or generating safer and convenient model systems. Here, we developed an EBOV life cycle modeling system in which subviral particles can spontaneously propagate in cell culture. In addition, this system can be employed to rescue infectious virions of homologous or heterologous EBOV isolates using either sense or antisense viral RNA genomes. In summary, we developed a new tool for EBOV research.
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- 2021
8. Ebola virus VP35 has novel NTPase and helicase-like activities
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Hui Zhou, Qi Qian, Xiaotong Wang, Lei Yin, Yang Qiu, Qi Cheng, Ting Shu, Jin Zhong, Tianyu Gan, Xi Zhou, and Peng Bai
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viruses ,Amino Acid Motifs ,Filoviridae ,Viral Nonstructural Proteins ,Virus Replication ,medicine.disease_cause ,03 medical and health sciences ,Adenosine Triphosphate ,0302 clinical medicine ,Genetics ,medicine ,Humans ,Replicon ,Cells, Cultured ,RNA, Double-Stranded ,030304 developmental biology ,0303 health sciences ,Ebola virus ,biology ,Nucleic Acid Enzymes ,Viral Core Proteins ,DNA Helicases ,RNA ,Helicase ,RNA virus ,Hemorrhagic Fever, Ebola ,Nucleocapsid Proteins ,Ebolavirus ,Nucleoside-Triphosphatase ,biology.organism_classification ,Virology ,RNA silencing ,Nucleoproteins ,Viral replication ,biology.protein ,RNA, Viral ,RNA Helicases ,030217 neurology & neurosurgery ,Protein Binding - Abstract
Ebola virus (EBOV) is a non-segmented, negative-sense RNA virus (NNSV) in the family Filoviridae, and is recognized as one of the most lethal pathogens in the planet. For RNA viruses, cellular or virus-encoded RNA helicases play pivotal roles in viral life cycles by remodelling viral RNA structures and/or unwinding viral dsRNA produced during replication. However, no helicase or helicase-like activity has ever been found to associate with any NNSV-encoded proteins, and it is unknown whether the replication of NNSVs requires the participation of any viral or cellular helicase. Here, we show that despite of containing no conserved NTPase/helicase motifs, EBOV VP35 possesses the NTPase and helicase-like activities that can hydrolyse all types of NTPs and unwind RNA helices in an NTP-dependent manner, respectively. Moreover, guanidine hydrochloride, an FDA-approved compound and inhibitor of certain viral helicases, inhibited the NTPase and helicase-like activities of VP35 as well as the replication/transcription of an EBOV minigenome replicon in cells, highlighting the importance of VP35 helicase-like activity during EBOV life cycle. Together, our findings provide the first demonstration of the NTPase/helicase-like activity encoded by EBOV, and would foster our understanding of EBOV and NNSVs.
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- 2019
9. TRIM26 is a critical host factor for HCV replication and contributes to host tropism
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Yongfen Xu, Qiang Ding, Guigen Zhang, Yu Guo, Yimin Tong, Wanyin Tao, Jin Zhong, Mingzhe Guo, Xiaomin Zhao, Zhuo Zhou, Wensheng Wei, Qiheng Li, Tianyu Gan, Y. F. Liang, Lin Han, and Xiaoyou Hu
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viruses ,Hepatitis C virus ,Host tropism ,medicine.disease_cause ,03 medical and health sciences ,chemistry.chemical_compound ,Ubiquitin ,TANK-binding kinase 1 ,Virology ,medicine ,NS5B ,Research Articles ,030304 developmental biology ,Host factor ,0303 health sciences ,Multidisciplinary ,biology ,030302 biochemistry & molecular biology ,virus diseases ,SciAdv r-articles ,digestive system diseases ,Ubiquitin ligase ,chemistry ,biology.protein ,Ectopic expression ,Research Article - Abstract
A genome-wide screening revealed that TRIM26 is a host factor for HCV replication and a new determinant for host tropism., Hepatitis C virus (HCV) remains a major human pathogen that requires better understanding of virus-host interactions. In this study, we performed a genome-wide CRISPR-Cas9 screening and identified TRIM26, an E3 ligase, as a critical HCV host factor. Deficiency of TRIM26 specifically impairs HCV genome replication. Mechanistic studies showed that TRIM26 interacts with HCV-encoded NS5B protein and mediates its K27-linked ubiquitination at residue K51, and thus promotes the NS5B-NS5A interaction. Moreover, mouse TRIM26 does not support HCV replication because of its unique six–amino acid insert that prevents its interaction with NS5B. Ectopic expression of human TRIM26 in a mouse hepatoma cell line that has been reconstituted with other essential HCV host factors promotes HCV infection. In conclusion, we identified TRIM26 as a host factor for HCV replication and a new determinant of host tropism. These results shed light on HCV-host interactions and may facilitate the development of an HCV animal model.
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- 2021
10. Long non-coding RNA nuclear enriched abundant transcript 1 (NEAT1) modulates inhibitor of DNA binding 1 (ID1) to facilitate papillary thyroid carcinoma development by sponging microRNA-524-5p.
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Guansheng Liao, Zhuoya Huang, Tianyu Gan, Cong Wu, Xiaolong Wang, and Dexiang Li
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- 2022
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11. Identification of a novel replication-competent hepatitis C virus variant that confers the sofosbuvir resistance
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Steve Leumi, Mingzhe Guo, Jie Lu, Zhaoning Wang, Tianyu Gan, Lin Han, Jackline Ngari, Yimin Tong, Xiaogang Xiang, Qing Xie, Lanfeng Wang, and Jin Zhong
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Pharmacology ,Genotype ,Virology ,Drug Resistance, Viral ,Genetic Variation ,Humans ,Replicon ,Hepacivirus ,Sofosbuvir ,Antiviral Agents ,Hepatitis C - Abstract
Despite the excellent antiviral potency of direct-acting antivirals (DAAs) against hepatitis C virus (HCV), emergence of drug-resistant viral mutations remains a potential challenge. Sofobuvir (SOF), a nucleotide analog targeting HCV NS5B - RNA-dependent RNA polymerase (RdRp), constitutes a key component of many anti-HCV cocktail regimens and confers a high barrier for developing drug resistance. The serine to threonine mutation at the amino acid position 282 of NS5B (S282T) is the mostly documented SOF resistance-associated substitution (RAS), but severely hampers the virus fitness. In this study, we first developed new genotype 1b (GT1b) subgenomic replicon cells, denoted PR52D4 and PR52D9, directly from a GT1b clinical isolate. Next, we obtained SOF-resistant and replication-competent PR52D4 replicon by culturing the replicon cells in the presence of SOF. Sequencing analysis showed that the selected replicon harbored two mutations K74R and S282T in NS5B. Reverse genetics analysis showed that while PR52D4 consisting of either single mutation K74R or S282T could not replicate efficiently, the engineering of the both mutations led to a replication-competent and SOF-resistant PR52D4 replicon. Furthermore, we showed that the K74R mutation could also rescue the replication deficiency of the S282T mutation in Con1, another GT1b replicon as well as in JFH1, a GT2a replicon. Structural modeling analysis suggested that K74R might help maintain an active catalytic conformation of S282T by engaging with Y296. In conclusion, we identified the combination of two NS5B mutations S282T and K74R as a novel RAS that confers a substantial resistance to SOF while retains the HCV replication capacity.
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- 2022
12. IL-1β Enhances the Antiviral Effect of IFN-α on HCV Replication by Negatively Modulating ERK2 Activation
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Lin Han, Jin Zhong, Qingchao Li, Tao Yu, Hui Xiao, Peilan Lou, Yongfen Xu, Tianyu Gan, Liqing Ye, Guangxun Meng, Xia Jin, and Mingzhe Guo
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p38 mitogen-activated protein kinases ,medicine.medical_treatment ,Interleukin-1beta ,Context (language use) ,Hepacivirus ,Antiviral Agents ,Proinflammatory cytokine ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Humans ,STAT1 ,030304 developmental biology ,0303 health sciences ,biology ,Chemistry ,Kinase ,Interferon-alpha ,Inflammasome ,Hepatitis C ,3. Good health ,Infectious Diseases ,Cytokine ,030220 oncology & carcinogenesis ,biology.protein ,Cancer research ,Phosphorylation ,medicine.drug - Abstract
Chronic hepatitis C infection is a leading cause of liver cirrhosis, which is linked to chronic hepatic inflammation. While there are multiple studies detailing the proinflammatory role of interleukin-1β (IL-1β) in HCV-induced inflammasome signaling, the antiviral capacity of this cytokine has not been adequately investigated in the context of HCV infection or other members of Flaviridae. Our data indicated that IL-1β alone does not inhibit HCV replication, yet when in combination with IFN-α, it can boost the anti-HCV activity of IFN-α, which is mediated by augmented STAT1 tyrosine 701 phosphorylation. Through signaling inhibitor screening, we found that ERK2 kinase is directly linked to the enhanced activation of the STAT1 complex. Our study found that IL-1β negatively affects ERK2 phosphorylation, which suggests that IL-1β-mediated STAT1 tyrosine 701 phosphorylation employed kinase machinery of ERK2 other than JNK or P38 kinase. Our results identify IL-1β as a proinflammatory cytokine possessing wide spectrum synergistic antiviral capability via enhancing IFN-α-induced interferon-stimulated genes (ISGs) expression. A more nuanced understanding of the antiviral mechanisms of this important cytokine could facilitate the development of new therapeutic options.
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- 2020
13. A trivalent HCV vaccine elicits broad and synergistic polyclonal antibody response in mice and rhesus monkey
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Dongming Zhou, Xuesong Wang, Xi Yang, Qiang Sun, Zhong Huang, Jin Zhong, Tianyu Gan, Yu Yan, and Dapeng Li
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Viral Hepatitis Vaccines ,0301 basic medicine ,Genotype ,Hepacivirus ,Neutralization ,Mice ,Viral Proteins ,03 medical and health sciences ,0302 clinical medicine ,Antigen ,Immunity ,Splenocyte ,Animals ,Cells, Cultured ,Immunity, Cellular ,biology ,Gastroenterology ,Hepatitis C Antibodies ,biology.organism_classification ,Antibodies, Neutralizing ,Hepatitis C ,Macaca mulatta ,Virology ,030104 developmental biology ,Polyclonal antibodies ,Antibody Formation ,Immunology ,biology.protein ,030211 gastroenterology & hepatology ,Antibody - Abstract
ObjectiveDespite the development of highly effective direct-acting antivirals, a prophylactic vaccine is needed for eradicating HCV. A major hurdle of HCV vaccine development is to induce immunity against HCV with high genome diversity. We previously demonstrated that a soluble E2 (sE2) expressed from insect cells induces broadly neutralising antibodies (NAbs) and prevents HCV infection. The objective of this study is to develop a multivalent HCV vaccine to increase the antigenic coverage.DesignWe designed a trivalent vaccine containing sE2 from genotype 1a, 1b and 3a. Mice and rhesus macaques were immunised with monovalent or trivalent sE2 vaccine, and sera or purified immunoglobulin were assessed for neutralisation against a panel of cell culture-derived virion (HCVcc) of genotype 1–7 in cell culture. Splenocytes from the vaccinated macaques were assessed for HCV-specific T cell response.ResultsWe showed that the trivalent vaccine elicited pangenotypic NAbs in mice, which neutralised HCVcc of all the seven genotypes more potently than the monovalent vaccine. Further analyses demonstrated that each sE2 component of this trivalent vaccine elicited unique spectrum of NAbs which acted synergistically to inhibit HCV infection. Finally, the trivalent vaccine triggered stronger and more uniform multigenotypic neutralising antibody response than the monovalent vaccine in rhesus macaques.ConclusionsIn summary, we developed a trivalent HCV vaccine that induces broad and synergistic-acting neutralising antibodies in mice and non-human primates.
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- 2017
14. A profiling study of a newly developed HCVcc strain PR63cc's sensitivity to direct-acting antivirals
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Tianyu Gan, Wanyin Tao, Jin Zhong, and Jie Lu
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0301 basic medicine ,Simeprevir ,Ledipasvir ,Adenosine ,Pyrrolidines ,Daclatasvir ,Genotype ,030106 microbiology ,Hepacivirus ,Biology ,Antiviral Agents ,03 medical and health sciences ,chemistry.chemical_compound ,Virology ,Drug Discovery ,Drug Resistance, Viral ,medicine ,Humans ,Enzyme Inhibitors ,Pharmacology ,Sulfonamides ,Dasabuvir ,Imidazoles ,Valine ,Hepatitis C, Chronic ,Isoquinolines ,Ombitasvir ,030104 developmental biology ,chemistry ,Grazoprevir ,Paritaprevir ,Mutation ,Asunaprevir ,Carbamates ,Sofosbuvir ,medicine.drug - Abstract
The development of direct-acting antivirals (DAAs) has significantly improved hepatitis C virus (HCV) treatment. However, drug resistance remains a potential concern in the real-world DAA-based therapies. We previously developed a novel full-length genotype 2a HCVcc clone PR63cc directly from clinical isolates. Here in this study, we compared the sensitivity of PR63cc and JFH1 to 12 different DAAs most of which are either already in clinical use or in the late clinical development phase. For NS5B inhibitors, PR63cc and JFH1 displayed comparable sensitivity to nucleoside/nucleotide analogues sofosbuvir and 2'-C-methyladenosine, while PR63cc was 4-fold more sensitive than JFH1 to nesbuvir, a non-nucleoside inhibitor. Interestingly, PR63cc and JFH1 were both completely resistant to dasabuvir which efficiently inhibited the replication of genotype 1b HCV replicon. For NS5A inhibitors, while PR63cc was as sensitive as JFH1 to ombitasvir and velpatasvir, it was much more resistant than JFH1 to daclatasvir and ledipasvir, which was mainly due to methionine at amino acid residue 31 of NS5A. For NS3 inhibitors, PR63cc was generally less sensitive than JFH1 to simeprevir, grazoprevir, asunaprevir and paritaprevir. Serine at residue 67 of NS3 was identified to be a resistance-associated variant (RAV) for asunaprevir. Finally, we showed that PR63cc was more resistant than JFH1 to the asunaprevir/daclatasvir combination treatment. In summary, our study systemically analyzed the DAA sensitivity of a new HCVcc strain and identified critical RAVs. These results are not only important for monitoring the emergence of drug-resistant mutations of current DAA therapies, but also valuable for developing next-generation DAAs.
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- 2017
15. Long Noncoding RNA LINC00511 Promotes Cell Growth And Invasion In Triple-Negative Breast Cancer By Interacting With Snail [Retraction]
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Ruilei Liu, Liang Wang, Tianyu Gan, Tao Pan, Jianglong Huang, and Mingjun Bai
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Oncology - Published
- 2019
16. Study on the length of cable-free zone of wide cantilever cable stayed bridge with low pylon
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Keyu Fan, Shuqin Li, and Tianyu Gan
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Cantilever ,Computer simulation ,business.industry ,Bending moment ,Pylon ,Structural engineering ,Deformation (meteorology) ,Span (engineering) ,business ,Bridge (interpersonal) ,Tower ,Geology - Abstract
Low pylon cable-stayed bridge is a new type of composite bridge between girder bridge and traditional cable-stayed bridge. Because of its good mechanical properties, economic benefits and beautiful shape, low pylon cable-stayed bridge is widely used in highway and urban landscape bridges. In this paper, a wide and low pylon cable-stayed bridge under construction is taken as the research background, and the numerical simulation model is established by using the finite element analysis software MIDAS CIVIL. The influence of the length of the cable-free zone is studied. By changing the length of cable-free zone at the tower root and the length of cable-free zone in the middle of span, the influence of the length of non-cable zone on the deformation, bending moment, internal force and cable force of low pylon cable-stayed bridge at the completion stage is studied. The reasonable value range of non-cable zone length is obtained. The research results will provide theoretical guidance for the design and construction of similar projects.
- Published
- 2021
17. Construction and characterization of Genotype-3 hepatitis C virus replicon revealed critical genotype-3-specific polymorphism for drug resistance and viral fitness
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Xiaogang Xiang, Mingzhe Guo, Yongfen Xu, Jie Lu, Tianyu Gan, Qing Xie, and Jin Zhong
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0301 basic medicine ,Genotype ,viruses ,Hepatitis C virus ,030106 microbiology ,Genome, Viral ,Hepacivirus ,Drug resistance ,Viral Nonstructural Proteins ,Biology ,Virus Replication ,medicine.disease_cause ,03 medical and health sciences ,Cell Line, Tumor ,Virology ,Drug Resistance, Viral ,medicine ,Humans ,Replicon ,Phylogeny ,Pharmacology ,NS3 ,Polymorphism, Genetic ,Dose-Response Relationship, Drug ,RNA ,RNA virus ,biology.organism_classification ,Hepatitis C ,030104 developmental biology ,Amino Acid Substitution ,Viral replication ,Genetic Fitness - Abstract
Hepatitis C virus (HCV), a major causative agent of chronic hepatitis, is a positive-stranded RNA virus and has a high degree of genetic diversity due to its error-prone RNA-dependent RNA polymerase. Development of direct-acting antiviral agents (DAAs) has greatly improved the therapeutic outcome of chronic hepatitis C patients. However, naturally existing resistance-associated variants (RAVs) or occurrence of resistance-associated substitutions (RASs) in the HCV genome may impose a challenge to the long-term success of the DAA-based therapies. Genotype-3 HCV is the most difficult genotype to treat by DAAs, but the underlying molecular mechanisms remain to be explored. Here we developed a novel genotype-3a subgenomic replicon PR87A7 by screening a HCV cDNA pool amplified from a patient serum RNA. PR87A7 replicon displayed strong resistance to anti-NS3 DAAs, mainly owing to a genotype-3-specific polymorphism 168Q in NS3. Introduction of NS3 168Q into a genotype-2a JFH1 strain rendered resistance to anti-NS3 DAAs while greatly diminished the viral replication, and yet this fitness defect can be rescued by additional genotype-3-specific polymorphism. In conclusion, we developed a novel genotype-3a subgenomic replicon by a functional screening approach, and revealed genotype-3-specfic amino acid residues that confer resistance to anti-NS3 DAAs while retaining viral fitness.
- Published
- 2019
18. Novel Stable Ebola Virus Minigenome Replicon Reveals Remarkable Stability of the Viral Genome
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Tianyu Gan, Wanyin Tao, Jin Zhong, Mingzhe Guo, and Yongfen Xu
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0301 basic medicine ,Ebola virus ,Viral protein ,viruses ,Immunology ,Biology ,medicine.disease_cause ,Microbiology ,Virology ,Genome Replication and Regulation of Viral Gene Expression ,Nucleoprotein ,03 medical and health sciences ,RNA silencing ,030104 developmental biology ,Viral replication ,Viral life cycle ,RNA interference ,Insect Science ,medicine ,Replicon - Abstract
Ebola virus (EBOV) causes severe hemorrhagic fever in humans and other primates with a high case fatality rate. No approved drug or vaccine of EBOV is available, which necessitates better understanding of the virus life cycle. Studies on EBOV have been hampered because experimentations involving live virus are restricted to biosafety level 4 (BSL4) laboratories. The EBOV minigenome system has provided researchers with the opportunity to study EBOV under BSL2 conditions. Here, we developed a novel EBOV minigenome replicon which, to our knowledge, is the first EBOV cell culture system that can stably replicate and transcribe the EBOV minigenome. The minigenomic RNA harboring a Gaussia luciferase and hygromycin-resistant marker can replicate for months in a helper cell stably expressing viral nucleoprotein (NP), viral protein 35 (VP35), VP30, and L proteins. Quantification of viral RNA (vRNA), cRNA, and mRNA levels of the EBOV minigenome demonstrated that the stable EBOV replicon had much-more-active minigenome replication than previously developed transient-transfection-based EBOV minigenome systems, which recapitulate viral primary transcription more than genome replication. Interestingly, minigenome replication in the stable EBOV replicon cells was insensitive to interferon treatment or RNA interference. Moreover, RNase digestion of the replicon cell lysates revealed the remarkably stable nature of the EBOV minigenomic vRNA ribonucleoprotein complex, which may help improve understanding of EBOV persistence in convalescent patients. IMPORTANCE The scope and severity of the recent Ebola outbreak in Western Africa justified a more comprehensive investigation of the causative risk group 4 agent Ebola virus (EBOV). Study of EBOV replication and antiviral development can be facilitated by developing a cell culture system that allows experimentation under biosafety level 2 conditions. Here, we developed a novel stable EBOV minigenome replicon which, to our knowledge, is the first EBOV cell culture system that can stably replicate and transcribe the EBOV minigenome. The replicon system had more-active genome replication than previously developed transient-transfection-based EBOV minigenome systems, providing a convenient surrogate system to study EBOV replication. Furthermore, self-replicating minigenomic vRNA in the replicon cells displayed strong stability in response to interferon treatment, RNA silencing, and RNase digestion, which may provide an explanation for the persistence of EBOV in survivors.
- Published
- 2017
19. IL-1β Enhances the Antiviral Effect of IFN-α on HCV Replication by Negatively Modulating ERK2 Activation.
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Mingzhe Guo, Liqing Ye, Tao Yu, Lin Han, Qingchao Li, Peilan Lou, Tianyu Gan, Xia Jin, Hui Xiao, Guangxun Meng, Jin Zhong, and Yongfen Xu
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- 2020
- Full Text
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20. A trivalent HCV vaccine elicits broad and synergistic polyclonal antibody response in mice and rhesus monkey.
- Author
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Xuesong Wang, Yu Yan, Tianyu Gan, Xi Yang, Dapeng Li, Dongming Zhou, Qiang Sun, Zhong Huang, and Jin Zhong
- Subjects
VIRAL envelope proteins ,RHESUS monkeys ,ANTIBODY formation ,HEPATITIS A virus - Published
- 2019
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21. Novel Stable Ebola Virus Minigenome Replicon Reveals Remarkable Stability of the Viral Genome.
- Author
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Wanyin Tao, Tianyu Gan, Mingzhe Guo, Yongfen Xu, and Jin Zhong
- Subjects
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EBOLA virus , *VIRAL genomes , *BIOSAFETY , *CELL culture , *NUCLEOPROTEINS - Abstract
Ebola virus (EBOV) causes severe hemorrhagic fever in humans and other primates with a high case fatality rate. No approved drug or vaccine of EBOV is available, which necessitates better understanding of the virus life cycle. Studies on EBOV have been hampered because experimentations involving live virus are restricted to biosafety level 4 (BSL4) laboratories. The EBOV minigenome system has provided researchers with the opportunity to study EBOV under BSL2 conditions. Here, we developed a novel EBOV minigenome replicon which, to our knowledge, is the first EBOV cell culture system that can stably replicate and transcribe the EBOV minigenome. The minigenomic RNA harboring a Gaussia luciferase and hygromycinresistant marker can replicate for months in a helper cell stably expressing viral nucleoprotein (NP), viral protein 35 (VP35), VP30, and L proteins. Quantification of viral RNA (vRNA), cRNA, and mRNA levels of the EBOV minigenome demonstrated that the stable EBOV replicon had much-more-active minigenome replication than previously developed transient-transfection-based EBOV minigenome systems, which recapitulate viral primary transcription more than genome replication. Interestingly, minigenome replication in the stable EBOV replicon cells was insensitive to interferon treatment or RNA interference. Moreover, RNase digestion of the replicon cell lysates revealed the remarkably stable nature of the EBOV minigenomic vRNA ribonucleoprotein complex, which may help improve understanding of EBOV persistence in convalescent patients. IMPORTANCE The scope and severity of the recent Ebola outbreak in Western Africa justified a more comprehensive investigation of the causative risk group 4 agent Ebola virus (EBOV). Study of EBOV replication and antiviral development can be facilitated by developing a cell culture system that allows experimentation under biosafety level 2 conditions. Here, we developed a novel stable EBOV minigenome replicon which, to our knowledge, is the first EBOV cell culture system that can stably replicate and transcribe the EBOV minigenome. The replicon system had more-active genome replication than previously developed transient-transfection-based EBOV minigenome systems, providing a convenient surrogate system to study EBOV replication. Furthermore, self-replicating minigenomic vRNA in the replicon cells displayed strong stability in response to interferon treatment, RNA silencing, and RNase digestion, which may provide an explanation for the persistence of EBOV in survivors. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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22. TRIM26 is a critical host factor for HCV replication and contributes to host tropism.
- Author
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Yisha Liang, Guigen Zhang, Qiheng Li, Lin Han, Xiaoyou Hu, Yu Guo, Wanyin Tao, Xiaomin Zhao, Mingzhe Guo, Tianyu Gan, Yimin Tong, Yongfen Xu, Zhuo Zhou, Qiang Ding, Wensheng Wei, and Jin Zhong
- Subjects
- *
VIRAL tropism , *VIRAL nonstructural proteins , *MEDICAL sciences , *HEPATITIS C vaccines - Abstract
The article offers information about the TRIM26, a critical host factor for Hepatitis C virus (HCV) replication and contributes to host tropism. It mentions about the identification of TRIM26 as a host factor for HCV replication and a new determinant of host tropism. It discusses that HCV-host interactions facilitate the development of an HCV animal model.
- Published
- 2021
- Full Text
- View/download PDF
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