Virus research最新文献

{"title":"Characterization of antigenically dominant regions in the hemagglutinin protein of B/victoria-lineage influenza B virus using monoclonal antibody escape mutants","authors":"Yoko Matsuzaki ,&nbsp;Kanetsu Sugawara ,&nbsp;Yoko Kadowaki ,&nbsp;Yuko Kidoguchi ,&nbsp;Yoshitaka Shimotai ,&nbsp;Katsumi Mizuta","doi":"10.1016/j.virusres.2025.199598","DOIUrl":"10.1016/j.virusres.2025.199598","url":null,"abstract":"<div><div>As of 2024, B/Victoria-lineage strains have emerged as the predominant influenza B viruses globally. To elucidate the antigenic regions responsible for variation within this lineage, three monoclonal antibodies (MAbs) targeting the hemagglutinin (HA) protein were employed to generate escape mutants of the B/Victoria strain B/Aichi/20/99, which was isolated approximately 10 years after the B/Victoria and B/Yamagata lineages began cocirculating. A total of 45 escape mutants were obtained. Sequencing of their HA genes identified six amino acid substitutions at four sites within two key antigenic regions—the 160-loop and 190-helix—specifically, N165Y, N165S, K167R, and an asparagine insertion between residues 164 and 165 in the 160-loop; and K203R and K203N in the 190-helix (numbering is based on the B/Brisbane/60/2008 HA sequence). Hemagglutination inhibition (HI) assays revealed that two MAbs affected binding of both mutants with mutations in the 160-loop and those with a mutation at residue 203. Mutations in the 160-loop did not affect reactivity with antiserum against the parental B/Aichi/20/99 strain, whereas K203N substitution reduced antiserum reactivity, indicating the antigenic importance of this residue. Further HI analyses using eight B/Victoria lineage strains isolated between 1997 and 2021 showed that all three MAbs lost reactivity with strains isolated after 2016, while the antiserum demonstrated reduced reactivity. Notably, the current vaccine strain, B/Austria/1359417/2021, which harbors substitutions at positions 150 and 203, also exhibited diminished reactivity. These findings suggest that both the 150-loop and 190-helix constitute antigenically dominant sites that contribute to immune escape and the emergence of drift variants within the B/Victoria-lineage.</div></div>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":"358 ","pages":"Article 199598"},"PeriodicalIF":2.5,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144310501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The association between influenza infection and acute myocardial infarction: A comprehensive systematic review and meta-analysis","authors":"Xia Zhou ,&nbsp;Li Feng","doi":"10.1016/j.virusres.2025.199594","DOIUrl":"10.1016/j.virusres.2025.199594","url":null,"abstract":"<div><div>Influenza infection could be associated with several systemic complications, including acute myocardial infarction (AMI); however, evidence on this association remains inconsistent. This systematic review and meta-analysis examined the influenza-AMI link, temporal AMI risk post-infection, and in-hospital outcomes and mortality in influenza-infected AMI patients. We conducted a systematic search of PubMed, EMBASE, Cochrane Library, Scopus, and Web of Science. Observational studies and self-controlled case series (SCCS) designs, were included. Data were extracted and analyzed using random-effects models to calculate pooled odds ratios (ORs), incidence rate ratios (IRRs), and 95 % confidence intervals (CIs). Subgroup analyses were performed based on exposure definitions (laboratory-confirmed influenza vs. influenza-like illness [ILI]), study design, and temporal patterns of AMI risk. In-hospital outcomes, including mortality, complications, length of stay, and costs, were also evaluated. The meta-analysis included 17 studies. A significant association was found, with a pooled adjusted OR of 2.70 (95 % CI: 1.28–5.72). ILI showed a stronger association with AMI (aOR: 2.04; 95 % CI: 1.33–3.14) compared to laboratory-confirmed influenza. Temporal analyses from SCCS studies revealed a markedly increased risk of AMI within the first week post-infection, peaking in days 1–3 (IRR: 6.83; 95 % CI: 4.66–10.01) and gradually declining thereafter. Influenza-infected AMI patients had significantly worse in-hospital outcomes, including higher mortality (OR: 1.60; 95 % CI: 1.55–1.66), and multiorgan failure (OR: 2.90; 95 % CI: 2.79–3.01). Additionally, these patients experienced longer median hospital stays (8.8 days vs. 5.5 days) and higher hospitalization costs ($20,678 vs. $18,269) compared to non-influenza AMI patients. This study confirms a strong link between influenza and AMI, especially early post-infection. Influenza-infected AMI patients experience worse outcomes, longer hospital stays, and higher costs. These findings highlight the importance of influenza prevention strategies, including vaccination, particularly in high-risk groups, to reduce AMI risk and its cardiovascular burden.</div></div>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":"358 ","pages":"Article 199594"},"PeriodicalIF":2.5,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144276030","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Validation of signature molecular profiles of advanced HCV liver disease in hepatocellular carcinoma patients","authors":"In-Woo Park,&nbsp;Hope K. Fiadjoe,&nbsp;Tamara Hoteit,&nbsp;Pankaj Chaudhary","doi":"10.1016/j.virusres.2025.199593","DOIUrl":"10.1016/j.virusres.2025.199593","url":null,"abstract":"<div><div>Our previous transcriptome analysis revealed that hepatitis C virus (HCV) infection in hepatocytes regulates the expression of numerous hepatocellular genes in a liver disease stage-specific manner. Based on the fold changes at different stages and the known relevant function of the cellular genes with respect to hepatocellular carcinoma (HCC) and through comprehensive examination with various in silico assays, such as heatmap and volcano analysis for the differential expression, the Cancer Genome Atlas - Hepatocellular Carcinoma (TCGA-HCC) analysis, and molecular approaches, such as qRT-PCR, immunoblot analyses, we have chosen the two up-regulated genes - aldo-keto reductase family 1 member B10 (AKR1B10) and hexokinase domain containing 1 (HKDC1), and two down-regulated genes - glycine N-methyltransferase (GNMT) and C-type lectin domain family 4, member M (CLEC4M), and validated their differential expressions of the genes at disparate stages of liver disease with respect to the development of potential therapeutic targets against HCV-mediated hepatocellular carcinoma (HCC). These data suggested that the differentially expressed genes at various stages could serve as prognostic and diagnostic markers for liver disease progression and may also be utilized in developing therapeutic drugs.</div></div>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":"357 ","pages":"Article 199593"},"PeriodicalIF":2.5,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144258958","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification and evaluation of biomarkers for diagnosis of chronic hepatitis B using RNA-seq","authors":"Hong Hong ,&nbsp;Xintong Han ,&nbsp;Qiuxiang Hu ,&nbsp;Huafeng Song ,&nbsp;Bing Han","doi":"10.1016/j.virusres.2025.199589","DOIUrl":"10.1016/j.virusres.2025.199589","url":null,"abstract":"<div><h3>Background &amp; aim</h3><div>Chronic hepatitis B (CHB) is a global public health problem affecting hundreds of millions of people and is associated with significant morbidity and mortality of liver cancer. Exosomes originate from cells and their detection in biofluids provides valuable insights into cellular and tissue alterations, thus reflecting underlying pathological states. The aim of this study was to provide exosomal RNA biomarkers of CHB and develop a machine learning model for the non-invasive diagnosis of CHB patients.</div></div><div><h3>Methods</h3><div>The differentially expressed genes (DEGs) were screened according to the RNA-seq data of normal and CHB liver tissues. The biomarkers were selected according to the analysis of pathway enrichment and functional annotation. The correlation of biomarkers’ expression level with the inflammation stage of CHB patients was analyzed. The non-invasive diagnostic value of the potential RNA biomarkers was evaluated by checking their different expression level in the plasma exosome of healthy individuals and CHB patients. A machine learning model was constructed to diagnose CHB by combining three identified biomarkers.</div></div><div><h3>Results</h3><div>A total of 1,006 differential expressed genes (569 upregulated and 437 downregulated) were screened between normal and CHB tissues. The GO and KEGG results showed the DEGs were mainly enriched in inflammation-related pathways. Among these genes, the expression of 4 upregulated genes and 27 downregulated genes showed consistent trends with the inflammation stage utilizing an independent CHB dataset. Three (<em>PXN-AS1, RAD9A, SLC17A9</em>) of 27 downregulated genes were found significantly decreased in plasma exosome of CHB patients. ROC analysis revealed that <em>PXN-AS1, RAD9A</em> and <em>SLC17A9</em> exhibited moderate diagnostic performance in distinguishing CHB from healthy controls, with AUC values of 0.743, 0.762, and 0.665 respectively. A machine learning model, Adaboost classifier, was constructed to detect CHB by combining exosomal expression of <em>PXN-AS1, RAD9A</em> and <em>SLC17A9</em>. The AUC of the model was 0.983 and 0.924 for CHB detection in train and test dataset respectively.</div></div><div><h3>Conclusion</h3><div>Based on multiple RNA-seq data of tissues and plasma exosomes, we identified <em>PXN-AS1, RAD9A, SLC17A9</em> as diagnostic biomarkers for CHB detection. The model based on three biomarkers showed potential diagnostic value for detecting CHB. Additional validation with a larger sample size is essential to thoroughly assess the reliability of these three biomarkers and the model's performance.</div></div>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":"358 ","pages":"Article 199589"},"PeriodicalIF":2.5,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144249826","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enterovirus 71 structural viral protein 1 promotes the expression of PMP22 through m6A modification in mouse Schwann cells","authors":"Qiuyan Peng ,&nbsp;Guangming Liu ,&nbsp;Danping Zhu ,&nbsp;Suyun Li ,&nbsp;Sida Yang ,&nbsp;Peiqing Li ,&nbsp;Yingxian Yin ,&nbsp;Dandan Hu","doi":"10.1016/j.virusres.2025.199590","DOIUrl":"10.1016/j.virusres.2025.199590","url":null,"abstract":"<div><h3>Purpose</h3><div>Enterovirus 71 (EV71) is one of the enteroviruses that causes hand-foot-and-mouth disease (HFMD). This study aims to investigate the role of EV71 structural viral protein 1 (VP1) in mouse Schwann cells.</div></div><div><h3>Methods</h3><div>An EV71 VP1-expressing vector was generated and transfected into mouse Schwann cells (MSCs). Small interfering RNAs against methyltransferase-like protein 14 (METTL14) and YTH N⁶-Methyladenosine RNA Binding Protein 1 (YTHDF1) were used to knock down the expressions of METTL14 and YTHDF1 in MSCs to investigate their roles in peripheral myelin protein 22 (PMP22) expression. Real-time PCR and Western blot analysis were performed to determine the expressions of PMP22 and m⁶A modification-associated proteins.</div></div><div><h3>Results</h3><div>EV71-VP1 over-expression significantly increased the expressions of transmethylase METTL3/14 and m⁶A methylation recognition protein YTHDC1 and YTHDF1/2/3 in MSCs. On the contrary, the level of demethylase FTO, but not ALKBH5, was obviously decreased in VP1-over-expressed MSCs. Furthermore, 3-DZA inhibited expressions of METTL3/14 and YTHDF1/2 in VP1-over-expressed MSCs, indicating METTL3/14 and YTHDF1/2 were the key m⁶A-modification-related genes regulated by VP1. In addition, deficiency of METTL14 or YTHDF1 contracted the up-regulation of PMP22 induced by VP1 overexpression in MSCs.</div></div><div><h3>Conclusions</h3><div>VP1 up-regulated PMP22 via m6A modification in MSCs, which were mainly affected by METTL14 and YTHDF1.</div></div>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":"358 ","pages":"Article 199590"},"PeriodicalIF":2.5,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144249825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preparation and pharmacokinetic evaluation of Staphylococcus phage COP-80B for treatment of periprosthetic joint infections in a mouse model","authors":"Vida Štilec ,&nbsp;Monika Marušić ,&nbsp;Nika Janež ,&nbsp;Urban Bezeljak ,&nbsp;Lucija Rebula ,&nbsp;Maja Leskovec ,&nbsp;Rihard Trebše ,&nbsp;Simon Horvat ,&nbsp;Matjaž Peterka","doi":"10.1016/j.virusres.2025.199592","DOIUrl":"10.1016/j.virusres.2025.199592","url":null,"abstract":"<div><div>Phage therapy has recently attracted significant attention as a potential treatment for periprosthetic joint infections, yielding promising outcomes in several compassionate use cases. The absence of standardized treatment protocols is partly attributable to insufficient pharmacokinetic data regarding relevant phage administration routes and dosages. Another neglected aspect is the scalable manufacturing of pharmaceutical-grade phage preparations for preclinical testing. In this study, we address both challenges and present a scalable phage production process for the <em>Staphylococcus epidermidis</em>-specific phage COP-80B We prepared a highly purified phage suspension, as verified through qPCR, HPLC, NTA and short-read sequencing, which was used in a preclinical pharmacokinetic study in an uninfected mice model. Using a plaque assay, we determined phage concentrations in mouse organs over time after intraperitoneal and intra-articular application of 10⁹ phages. Intra-articularly administered phages persisted in the periarticular tissue for several days, entered the systemic circulation and were subsequently cleared from the liver and spleen. Conversely, intraperitoneally administered phages did not reach the intra-articular space. No adverse events and no changes in hematological parameters were observed in mice after phage application by either route, confirming the safety of a single-dose application. Our results emphasize the importance of local phage administration for sustained presence in periarticular tissue and provide valuable pharmacokinetic data to support the development of optimized treatment protocols for periprosthetic joint infections.</div></div>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":"357 ","pages":"Article 199592"},"PeriodicalIF":2.5,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144209644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of a multi-segmented rod-shaped mycovirus within the order Martellivirales largely accommodating plant viruses","authors":"Mika Yoshioka ,&nbsp;Akihito Fukudome ,&nbsp;Yuto Chiba ,&nbsp;Daisuke Hagiwara ,&nbsp;Syun-ichi Urayama","doi":"10.1016/j.virusres.2025.199591","DOIUrl":"10.1016/j.virusres.2025.199591","url":null,"abstract":"<div><div>The order <em>Martellivirales</em> in the <em>Riboviria</em> realm includes seven established families. The viruses in this order have a single-stranded positive-sense RNA genome and infect animals, plants, or fungi. In this study, we characterized Aspergillus flavus vivivirus 1 (AfViV1), an RNA virus infecting <em>Aspergillus flavus</em> that presumably belongs to the proposed “Viviviridae” family in the <em>Martellivirales</em> order. In previous reports, multiple RNA-dependent RNA polymerase (RdRP) sequences related to “Viviviridae” were mainly identified from metatranscriptome data. However, their virological characteristics were not disclosed. Our analysis showed that the AfViV1 virion exhibited a rod-shaped structure with varying lengths and identified the coat protein (CP) encoded by <em>RNA12</em> of AfViV1. Using the AfViV1-CP sequence, we detected several potential CP sequences from viruses in the suggested “Viviviridae“ family based on sequence read archive (SRA) data. These data suggest that viruses in this family have similar rod-shaped structures. Interestingly, the AfViV1-CP amino acid sequence was not significantly similar to the known viral CP. However, the predicted structure was similar to rod-shaped viruses in the <em>Potyviridae</em> (<em>Patatavirales</em>) and <em>Closteroviridae</em> (<em>Martellivirales</em>) families (and orders). Our analysis describes the first multi-segmented fungal ssRNA virus with rod-shaped particles and expands the morphological diversity of fungal RNA viruses. Additionally, this study highlights the similarities between fungal and plant viruses, suggesting their deep relationships concerning host range, host adaptation, and more.</div></div>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":"357 ","pages":"Article 199591"},"PeriodicalIF":2.5,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144200117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recombinant adeno-associated virus 2-mediated miRNA-199 suppression vector alleviates dextran sulfate sodium-induced ulcerative colitis in mice","authors":"Wang Shanshan ,&nbsp;Zhao Yu","doi":"10.1016/j.virusres.2025.199588","DOIUrl":"10.1016/j.virusres.2025.199588","url":null,"abstract":"<div><h3>Aim</h3><div>Mouse colonic tissue was transfected with a recombinant adeno-associated virus (rAAV) 2 vector. We aimed to determine whether the rAAV vector could mediate gene expression in the colonic tissue and the role of microRNA (miRNA)-199a-5p in regulating the colonic inflammatory response in dextran sulfate sodium (DSS)-treated mice.</div></div><div><h3>Methods</h3><div>Different transfection methods and transfection times were found to be the most effective for mouse colonic tissue. The rAAV-miRNA-199a-5p vector (and control) was transfected into the colonic tissue of a mouse model of DSS-induced colitis. PCR was used to quantify miRNA and mRNA expression levels, and the TUNNEL assay was used to identify cellular regulation and histological alterations in colonic tissues.</div></div><div><h3>Results</h3><div>At three weeks following transfection, rAAV produced a higher transfection efficiency in colonic tissues via enucleation than via caudal vein injection and intraperitoneal injection. The colonic inflammatory response and apoptosis in mouse colonic tissues were reduced by miRNA-199a-5p inhibition.</div></div><div><h3>Conclusion</h3><div>rAAV can be used as a vector to inhibit gene expression in mouse colonic tissues. In mice with colitis, the rAAV-mediated suppression of miRNA-199a-5p reduces the inflammatory response.</div></div>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":"357 ","pages":"Article 199588"},"PeriodicalIF":2.5,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144143626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibition of Semliki Forest virus replication with long double-stranded RNA in Aedes albopictus cells","authors":"Alejandra Centurión ,&nbsp;Bodunrin Omokungbe ,&nbsp;Sabrina Stiehler ,&nbsp;Andreas Vilcinskas ,&nbsp;Kornelia Hardes","doi":"10.1016/j.virusres.2025.199584","DOIUrl":"10.1016/j.virusres.2025.199584","url":null,"abstract":"<div><div>Arthropod-borne viruses represent an increasing threat to the global health system, requiring the development of novel and sustainable control strategies to reduce the risk of arboviral infections. RNA interference (RNAi) offers a potential approach to directly prevent viral replication within vectors due to its specificity in gene silencing. In this study, we evaluated the efficacy of long double-stranded RNAs (dsRNAs) targeting six regions of the Semliki Forest virus (SFV) genome in <em>Aedes albopictus</em> U4.4 cells. The antiviral efficiency of dsRNA alone is low, therefore we evaluated its use after complexing with the K4 Transfection System (K4). A cytotoxicity assay based on ATP quantification showed that both uncomplexed and complexed dsRNA had no cytotoxic effects on U4.4 cells at a concentration up to 2 ng/µL. Complexed dsRNA achieved higher antiviral efficacy, significantly reducing viral replication compared to uncomplexed dsRNA. We found that complexed dsRNA retained its antiviral activity when challenged with SFV up to 72 h post-transfection. Among our synthesized dsRNA constructs, nsP4-dsRNA in complex with K4 led to an 80 % reduction in viral replication at 72 h post-infection at 0.5 ng/µL. Using RT-qPCR, we confirmed a significant 32.2 % reduction of nsP4 mRNA after transfection of complexed nsP4-dsRNA. Dose response assays showed that complexed dsRNAs with a concentration of 0.5 ng/µL are effective for viral reduction. Our results highlight the importance of efficient dsRNA delivery and selection of critical viral targets, such as nsP4, for successful RNAi-mediated viral suppression. This work elucidates the potential of dsRNAs to target Semliki Forest virus replication, highlighting viral gene targeting as a viable strategy for RNAi-based suppression of arboviral replication.</div></div>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":"357 ","pages":"Article 199584"},"PeriodicalIF":2.5,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144102633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Large-scale prediction shows that the dominant structure of the HIV-1 domain closed by the U5-AUG duplex contains the alternative SDa hairpin, and the domain variant without SD is rare","authors":"M.I. Zarudnaya,&nbsp;A.L. Potyahaylo,&nbsp;L.G. Gorb","doi":"10.1016/j.virusres.2025.199581","DOIUrl":"10.1016/j.virusres.2025.199581","url":null,"abstract":"<div><div>Using several models of the HIV-1 5′ leader, it was shown that the domain containing the structural elements that regulate the processes of dimerization and genome packaging, as well as the initiation of reverse transcription, is closed by the U5-AUG duplex. However, there is no consensus in the literature on the structure of the upper part of this domain. Currently, the model proposed by Keane et al. in 2015 is dominant, although the question of whether it is general structure or specific to the experimental HIV-1 genome NL4–3 of subtype B remains open. To clarify this issue, we conducted large-scale <em>in silico</em> studies on the secondary structure of the domain closed by the U5-AUG duplex in 2754 HIV-1 genomes of different subtypes. Our investigation showed that the proportion of HIV-1 genomes in which the structure of the domain under study is similar to that in Keane et al. model is low. It forms mainly in HIV-1 genomes of subtype B with the frequency of 3.8 % in the optimal foldings or foldings with the energy increment of the lowest change in free energy (ΔΔG)&lt;1.0 kcal/mol. In particular, certain base changes in common SD hairpin or base changes stabilizing Psi hairpin contribute to the formation of this domain variant. The dominant structure of the domain closed by the U5-AUG duplex is similar to that in Wilkinson et al. model (2008) but with the alternative SD hairpin. We found also new variants of this domain, which occur in foldings with ΔΔG&lt;1.0 kcal/mol and may co-exist with dominant structure. However, it is possible that the variants of the domain closed by the U5-AUG duplex similar to Wilkinson et al. or Keane et al. models are formed only in the early stages of HIV-1 replication, while in the late stage (in the presence of nucleocapsid protein) the domain adopts structure similar to that in Sakuragi et al. (2012) model and the initiation of the reverse transcription occurs just in this structure. Extreme conservation of GACGC-GCGUC duplex, proposed in Sakuragi et al. model, supports this assumption.</div></div>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":"357 ","pages":"Article 199581"},"PeriodicalIF":2.5,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144095156","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}