Virologica SinicaPub Date : 2024-08-01DOI: 10.1016/j.virs.2024.06.002
{"title":"Correlation between circulating T follicular helper cell levels after infection and a decreased risk of COVID-19 re-infection","authors":"","doi":"10.1016/j.virs.2024.06.002","DOIUrl":"10.1016/j.virs.2024.06.002","url":null,"abstract":"","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"39 4","pages":"Pages 699-701"},"PeriodicalIF":5.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1995820X24000816/pdfft?md5=427af723012209ef3b391a246ed4582e&pid=1-s2.0-S1995820X24000816-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141296829","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Virologica SinicaPub Date : 2024-08-01DOI: 10.1016/j.virs.2024.06.003
{"title":"Detection of HBV DNA integration in plasma cell-free DNA of different HBV diseases utilizing DNA capture strategy","authors":"","doi":"10.1016/j.virs.2024.06.003","DOIUrl":"10.1016/j.virs.2024.06.003","url":null,"abstract":"<div><p>The landscape of hepatitis B virus (HBV) integration in the plasma cell-free DNA (cfDNA) of HBV-infected patients with different stages of liver diseases [chronic hepatitis B (CHB), liver cirrhosis (LC), and hepatocellular carcinoma (HCC)] remains unclear. In this study, we developed an improved strategy for detecting HBV DNA integration in plasma cfDNA, based on DNA probe capture and next-generation sequencing. Using this optimized strategy, we successfully detected HBV integration events in chimeric artificial DNA samples and HBV-infected HepG2-NTCP cells at day one post infection, with high sensitivity and accuracy. The characteristics of HBV integration events in the HBV-infected HepG2-NTCP cells and plasma cfDNA from HBV-infected individuals (CHB, LC, and HCC) were further investigated. A total of 112 and 333 integration breakpoints were detected in the HepG2-NTCP cells and 22 out of 25 (88%) clinical HBV-infected samples, respectively. <em>In vivo</em> analysis showed that the normalized number of support unique sequences (<em>nnsus</em>) in HCC was significantly higher than in CHB or LC patients (<em>P</em> values < 0.05). All integration breakpoints are randomly distributed on human chromosomes and are enriched in the HBV genome around nt 1800. The majority of integration breakpoints (61.86%) are located in the gene-coding region. Both non-homologous end-joining (NHEJ) and microhomology-mediated end-joining (MMEJ) interactions occurred during HBV integration across the three different stages of liver diseases. Our study provides evidence that HBV DNA integration can be detected in the plasma cfDNA of HBV-infected patients, including those with CHB, LC, or HCC, using this optimized strategy.</p></div>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"39 4","pages":"Pages 655-666"},"PeriodicalIF":5.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1995820X24000828/pdfft?md5=c59234e1ed45ce52f4e2926238f136d0&pid=1-s2.0-S1995820X24000828-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141296830","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Virologica SinicaPub Date : 2024-08-01DOI: 10.1016/j.virs.2024.06.009
{"title":"AIMP2 restricts EV71 replication by recruiting SMURF2 to promote the degradation of 3D polymerase","authors":"","doi":"10.1016/j.virs.2024.06.009","DOIUrl":"10.1016/j.virs.2024.06.009","url":null,"abstract":"<div><p>Hand, foot and mouth disease (HFMD), mainly caused by enterovirus 71 (EV71), has frequently occurred in the Asia-Pacific region, posing a significant threat to the health of infants and young children. Therefore, research on the infection mechanism and pathogenicity of enteroviruses is increasingly becoming important. The 3D polymerase, as the most critical RNA-dependent RNA polymerase (RdRp) for EV71 replication, is widely targeted to inhibit EV71 infection. In this study, we identified a novel host protein, AIMP2, capable of binding to 3D polymerase and inhibiting EV71 infection. Subsequent investigations revealed that AIMP2 recruits the E3 ligase SMURF2, which mediates the polyubiquitination and degradation of 3D polymerase. Furthermore, the antiviral effect of AIMP2 extended to the CVA16 and CVB1 serotypes. Our research has uncovered the dynamic regulatory function of AIMP2 during EV71 infection, revealing a novel antiviral mechanism and providing new insights for the development of antienteroviral therapeutic strategies.</p></div>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"39 4","pages":"Pages 632-644"},"PeriodicalIF":5.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1995820X24001081/pdfft?md5=8e9849117e1716838af0defc408ef1c7&pid=1-s2.0-S1995820X24001081-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141471094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Virologica SinicaPub Date : 2024-08-01DOI: 10.1016/j.virs.2024.06.007
{"title":"Measures of insulin resistance and beta cell function before and after treatment of HCV infection","authors":"","doi":"10.1016/j.virs.2024.06.007","DOIUrl":"10.1016/j.virs.2024.06.007","url":null,"abstract":"<div><p>The association between chronic HCV infection and type 2 diabetes mellitus (T2DM) has been established; however, there is limited research on β-cell function particularly in the pre-diabetic population. Here, we evaluated indices of β-cell function and insulin sensitivity across the spectrum from normal glucose tolerance to T2DM in individuals with and without chronic hepatitis C (CHC), and the effects of antiviral treatments on these variables. A total of 153 non-cirrhotic, non-fibrotic CHC patients with a BMI <25 were enrolled in the study. Among them, 119 were successfully treated with either direct acting antiviral (DAA) drugs or pegylated interferon/ribavirin (IFN/RBV) anti-HCV therapy. Fasting state- and oral glucose tolerance test (OGTT)-derived indexes were used to evaluate β-cell function and insulin sensitivity. Among all subjects, 19 (13%) had T2DM and 21% exhibited pre-diabetes including 8% isolated impaired fasting glucose (IFG) and 13% combined IFG and impaired glucose tolerance (IGT). Early and total insulin secretion adjusted for the degree of insulin resistance were decreased in pre-diabetic CHC patients compared to HCV-uninfected individuals. Viral eradication through DAA or IFN/RBV therapy demonstrated positive impacts on insulin sensitivity and β-cell function in CHC patients who achieved sustained virologic response (SVR), regardless of fasting or OGTT state. These findings emphasize the role of HCV in the development of β-cell dysfunction, while also suggesting that viral eradication can improve insulin secretion, reverse insulin resistance, and ameliorate glycemic control. These results have important implications for managing pre-diabetic CHC patients and could prevent diabetes-related clinical manifestations and complications.</p></div>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"39 4","pages":"Pages 667-674"},"PeriodicalIF":5.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1995820X24001056/pdfft?md5=0b6aa3ce41faac910b24c120f2e9888b&pid=1-s2.0-S1995820X24001056-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141477521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Virologica SinicaPub Date : 2024-08-01DOI: 10.1016/j.virs.2024.07.002
{"title":"A quadrivalent norovirus vaccine based on a chimpanzee adenovirus vector induces potent immunity in mice","authors":"","doi":"10.1016/j.virs.2024.07.002","DOIUrl":"10.1016/j.virs.2024.07.002","url":null,"abstract":"<div><p>Norovirus (NoV) infection is a major cause of gastroenteritis worldwide. The virus poses great challenges in developing vaccines with broad immune protection due to its genetic and antigenic diversity. To date, there are no approved NoV vaccines for clinical use. Here, we aimed to develop a broad-acting quadrivalent NoV vaccine based on a chimpanzee adenovirus vector, AdC68, carrying the major capsid protein (VP1) of noroviral GI and GII genotypes. Compared to intramuscular (i.m.), intranasal (i.n.), or other prime-boost immunization regimens (i.m. + i.m., i.m. + i.n., i.n. + i.m.), AdC68-GI.1-GII.3 (E1)-GII.4-GII.17 (E3), administered via i.n. + i.n. induced higher titers of serum IgG antibodies and higher IgA antibodies in bronchoalveolar lavage fluid (BALF) and saliva against the four homologous VP1s in mice. It also significantly stimulated the production of blocking antibodies against the four genotypes. In response to re-stimulation with virus-like particles (VLP)-GI.1, VLP-GII.3, VLP-GII.4, and VLP-GII.17, the quadrivalent vaccine administered according to the i.n. + i.n. regimen effectively triggered specific cell-mediated immune responses, primarily characterized by IFN-γ secretion. Furthermore, the preparation of this novel quadrivalent NoV vaccine requires only a single recombinant adenovirus to provide broad preventive immunity against the major GI/GII epidemic strains, making it a promising vaccine candidate for further development.</p></div>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"39 4","pages":"Pages 675-684"},"PeriodicalIF":5.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1995820X24001123/pdfft?md5=c85be2d64b45a21de8d2d0d74f5ea576&pid=1-s2.0-S1995820X24001123-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141601929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Virologica SinicaPub Date : 2024-08-01DOI: 10.1016/j.virs.2024.07.001
{"title":"Structural and functional insights into the 2′-O-methyltransferase of SARS-CoV-2","authors":"","doi":"10.1016/j.virs.2024.07.001","DOIUrl":"10.1016/j.virs.2024.07.001","url":null,"abstract":"<div><p>A unique feature of coronaviruses is their utilization of self-encoded nonstructural protein 16 (nsp16), 2′-O-methyltransferase (2′-O-MTase), to cap their RNAs through ribose 2′-O-methylation modification. This process is crucial for maintaining viral genome stability, facilitating efficient translation, and enabling immune escape. Despite considerable advances in the ultrastructure of SARS-CoV-2 nsp16/nsp10, insights into its molecular mechanism have so far been limited. In this study, we systematically characterized the 2′-O-MTase activity of nsp16 in SARS-CoV-2, focusing on its dependence on nsp10 stimulation. We observed cross-reactivity between nsp16 and nsp10 in various coronaviruses due to a conserved interaction interface. However, a single residue substitution (K58T) in SARS-CoV-2 nsp10 restricted the functional activation of MERS-CoV nsp16. Furthermore, the cofactor nsp10 effectively enhanced the binding of nsp16 to the substrate RNA and the methyl donor S-adenosyl-<span>l</span>-methionine (SAM). Mechanistically, His-80, Lys-93, and Gly-94 of nsp10 interacted with Asp-102, Ser-105, and Asp-106 of nsp16, respectively, thereby effectively stabilizing the SAM binding pocket. Lys-43 of nsp10 interacted with Lys-38 and Gly-39 of nsp16 to dynamically regulate the RNA binding pocket and facilitate precise binding of RNA to the nsp16/nsp10 complex. By assessing the conformational epitopes of nsp16/nsp10 complex, we further determined the critical residues involved in 2′-O-MTase activity. Additionally, we utilized an <em>in vitro</em> biochemical platform to screen potential inhibitors targeting 2′-O-MTase activity. Overall, our results significantly enhance the understanding of viral 2′-O methylation process and mechanism, providing valuable targets for antiviral drug development.</p></div>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"39 4","pages":"Pages 619-631"},"PeriodicalIF":5.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1995820X24001111/pdfft?md5=0d34dd7cd1a804b2d4b14371b5d2f14e&pid=1-s2.0-S1995820X24001111-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141538721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Virologica SinicaPub Date : 2024-08-01DOI: 10.1016/j.virs.2024.05.001
{"title":"Design of antiviral AGO2-dependent short hairpin RNAs","authors":"","doi":"10.1016/j.virs.2024.05.001","DOIUrl":"10.1016/j.virs.2024.05.001","url":null,"abstract":"<div><p>The increasing emergence and re-emergence of RNA virus outbreaks underlines the urgent need to develop effective antivirals. RNA interference (RNAi) is a sequence-specific gene silencing mechanism that is triggered by small interfering RNAs (siRNAs) or short hairpin RNAs (shRNAs), which exhibits significant promise for antiviral therapy. AGO2-dependent shRNA (agshRNA) generates a single-stranded guide RNA and presents significant advantages over traditional siRNA and shRNA. In this study, we applied a logistic regression algorithm to a previously published chemically siRNA efficacy dataset and built a machine learning-based model with high predictive power. Using this model, we designed siRNA sequences targeting diverse RNA viruses, including human enterovirus A71 (EV71), Zika virus (ZIKV), dengue virus 2 (DENV2), mouse hepatitis virus (MHV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and transformed them into agshRNAs. We validated the performance of our agshRNA design by evaluating antiviral efficacies of agshRNAs in cells infected with different viruses. Using the agshRNA targeting EV71 as an example, we showed that the anti-EV71 effect of agshRNA was more potent compared with the corresponding siRNA and shRNA. Moreover, the antiviral effect of agshRNA is dependent on AGO2-processed guide RNA, which can load into the RNA-induced silencing complex (RISC). We also confirmed the antiviral effect of agshRNA <em>in vivo</em>. Together, this work develops a novel antiviral strategy that combines machine learning-based algorithm with agshRNA design to custom design antiviral agshRNAs with high efficiency.</p></div>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"39 4","pages":"Pages 645-654"},"PeriodicalIF":5.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1995820X24000695/pdfft?md5=1b7e4a5987f65a53da869d0a2cd24d05&pid=1-s2.0-S1995820X24000695-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140909385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Virologica SinicaPub Date : 2024-08-01DOI: 10.1016/j.virs.2024.05.008
{"title":"Seroprevalence of neutralizing antibodies against HFMD associated enteroviruses among healthy individuals in Shanghai, China, 2022","authors":"","doi":"10.1016/j.virs.2024.05.008","DOIUrl":"10.1016/j.virs.2024.05.008","url":null,"abstract":"","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"39 4","pages":"Pages 694-698"},"PeriodicalIF":5.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1995820X24000774/pdfft?md5=860275c4880f43846772ca1a29f49c8a&pid=1-s2.0-S1995820X24000774-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141158614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Virologica SinicaPub Date : 2024-08-01DOI: 10.1016/j.virs.2024.05.010
{"title":"Diverse genotypes of norovirus genogroup I and II contamination in environmental water in Thailand during the COVID-19 outbreak from 2020 to 2022","authors":"","doi":"10.1016/j.virs.2024.05.010","DOIUrl":"10.1016/j.virs.2024.05.010","url":null,"abstract":"<div><p>Noroviruses (NoVs) are the most significant viral pathogens associated with waterborne and foodborne outbreaks of nonbacterial acute gastroenteritis in humans worldwide. This study aimed to investigate the prevalence and diversity of NoVs contaminated in the environmental water in Chiang Mai, Thailand. A total of 600 environmental water samples were collected from ten sampling sites in Chiang Mai from July 2020 to December 2022. The presence of NoV genogroups I (GI), GII, and GIV were examined using real-time RT-PCR assay. The genotype of the virus was determined by nucleotide sequencing and phylogenetic analysis. The results showed that NoV GI and GII were detected at 8.5% (51/600) and 11.7% (70/600) of the samples tested, respectively. However, NoV GIV was not detected in this study. NoV circulated throughout the year, with a higher detection rate during the winter season. Six NoV GI genotypes (GI.1-GI.6) and eight NoV GII genotypes (GII.2, GII.3, GII.7, GII.8, GII.10, GII.13, GII.17, and GII.21) were identified. Among 121 NoV strains detected, GII.17 was the most predominant genotype (24.8%, 30 strains), followed by GII.2 (21.5%, 26 strains), GI.3 (17.4%, 21 strains), and GI.4 (16.5%, 20 strains). Notably, NoV GII.3, GII.7, GII.8, and GII.10 were detected for the first time in water samples in this area. This study provides insight into the occurrence and seasonal pattern of NoV along with novel findings of NoV strains in environmental water in Thailand during the COVID-19 outbreak. Our findings emphasize the importance of further surveillance studies to monitor viral contamination in environmental water.</p></div>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"39 4","pages":"Pages 556-564"},"PeriodicalIF":5.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1995820X24000798/pdfft?md5=ba594f061369ca489e52f30579e769ab&pid=1-s2.0-S1995820X24000798-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141186153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}