Journal of Virology最新文献

{"title":"Cholesterol 25-hydroxylase inhibits Newcastle disease virus replication by enzyme activity-dependent and direct interaction with nucleocapsid protein.","authors":"Guangmei Zhu, Xianchun Zong, Mengmeng Xiao, Dan Wang, Zhe Xu, Jingtao Hu, Guilian Yang, Yanlong Jiang, Wentao Yang, Haibin Huang, Chunwei Shi, Yan Zeng, Nan Wang, Xin Cao, Jianzhong Wang, Chunfeng Wang","doi":"10.1128/jvi.00428-25","DOIUrl":"https://doi.org/10.1128/jvi.00428-25","url":null,"abstract":"<p><p>Newcastle disease virus (NDV) is a significant enveloped virus within the Paramyxoviridae family, posing a major threat to the global poultry industry. Increasing evidence suggests that cholesterol-25-hydroxylase (CH25H) and its enzymatic product, 25-hydroxycholesterol (25HC), exhibit broad-spectrum antiviral activity properties by modulating lipid metabolism and various signaling pathways. However, the specific role of CH25H in regulating NDV infection and replication remains unclear. In this study, we demonstrate that CH25H significantly inhibits NDV replication by blocking viral entry through its enzymatic product, 25HC. Notably, a catalytic mutant of CH25H (CH25H-M), which lacks hydroxylase activity, still retains partial ability to inhibit NDV replication, suggesting the involvement of an enzyme-independent antiviral mechanism. Furthermore, we found that CH25H interacts with the viral nucleoprotein (NP), leading to a reduction in NP expression and inhibition of viral ribonucleoprotein (RNP) complex activity. These findings reveal that CH25H exerts antiviral effects through both enzyme-dependent and -independent mechanisms, providing new insights into its role in host defense and offering potential targets for the development of antiviral therapies.IMPORTANCECholesterol 25-hydroxylase (CH25H) is a multifunctional host protein that has been implicated in regulating the life cycles of various viruses. As a prototype of paramyxovirus, Newcastle disease virus (NDV) poses a significant threat to the global poultry industry, causing substantial economic losses. Uncovering the mechanisms of NDV-host interactions is crucial for unraveling the viral pathogenesis and the host immune response, which can drive the development of effective antiviral therapies. Here, we demonstrate that CH25H, whose expression is induced upon NDV infection, plays a pivotal role in restricting viral replication. Specifically, CH25H interacts with the viral NP and inhibits the viral RNP activity. These findings expand our understanding of CH25H's antiviral functions and offer new insights into virus-host interactions, providing potential targets for the development of novel antiviral drugs against NDV and related pathogens.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0042825"},"PeriodicalIF":4.0,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144023458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive maps of escape mutations from antibodies 10-1074 and 3BNC117 for Envs from two divergent HIV strains.","authors":"Caelan E Radford, Jesse D Bloom","doi":"10.1128/jvi.00195-25","DOIUrl":"https://doi.org/10.1128/jvi.00195-25","url":null,"abstract":"<p><p>Antibodies capable of neutralizing many strains of HIV are being explored as prophylactic and therapeutic agents, but viral escape mutations pose a major challenge. Efforts have been made to experimentally define the escape mutations from specific antibodies in specific viral strains, but it remains unclear how much the effects of mutations on neutralization differ among HIV strains. Here, we use pseudovirus deep mutational scanning to comprehensively map escape mutations from the V3 loop targeting antibody 10-1074 and the CD4-binding site targeting antibody 3BNC117 for both a clade A (BF520) and a clade B (TRO.11) HIV Envelope (Env). Mutations that escape neutralization by antibody 10-1074 are largely similar for the two Envs, but mutations that escape 3BNC117 differ greatly between Envs. Some differences in the effects of mutations on escape between Envs can be explained by strain-to-strain variation in mutational tolerance or potential N-linked glycosylation motifs, but other mutations have different effects on escape for unclear reasons. Overall, the extent to which measurements of mutational effects on antibody neutralization can be generalized across HIV strains differs among antibodies 10-1074 and 3BNC117.IMPORTANCEBroadly neutralizing antibodies are promising candidates as prophylactics and therapeutics for HIV. This study uses pseudoviruses to map all escape mutations for antibodies 10-1074 and 3BNC117 for the Envelope proteins from two different HIV strains. These maps can inform analyses of viral mutations observed in clinical trials and help understand how the escape mutations from these antibodies differ across HIV strains.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0019525"},"PeriodicalIF":4.0,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144015521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protein-S-nitrosylation of human cytomegalovirus pp65 reduces its ability to undermine cGAS.","authors":"Justin B Cox, Masatoshi Nukui, Eain A Murphy","doi":"10.1128/jvi.00481-25","DOIUrl":"https://doi.org/10.1128/jvi.00481-25","url":null,"abstract":"<p><p>Post-translational modifications (PTMs) are key regulators of various processes important for cell survival. These modifications are critical for dealing with stress conditions, such as those observed in disease states, and during infections with various pathogens. We previously reported that during infection of primary dermal fibroblasts, multiple human cytomegalovirus (HCMV)-encoded proteins were post-translationally modified by the addition of a nitric oxide group to cysteine residues, a modification called protein-S-nitrosylation. For example, tegument protein pp71 is nitrosylated, diminishing its ability to inhibit STING, a protein necessary for DNA virus immune response. Herein, we report that an additional HCMV tegument protein, pp65, responsible for the inhibition of cGAS is also modified by protein-S-nitrosylation on two cysteine residues. Utilizing site-directed mutagenesis to generate recombinant viruses that encode a pp65 that cannot be protein-S-nitrosylated, we evaluated the impact of this PTM on viral replication and how the virus impacts the cGAS/STING pathway. We report that the nitrosylation of pp65 negatively impacts its ability to block cGAS enzymatic functions. pp65 protein-S-nitrosylation mutants demonstrated a decrease in cGAS/STING-induced IRF3 and TBK1 phosphorylation. Additionally, we observed a reduction in IFN-β1 secretion in NuFF-1 cells expressing a nitrosylation-resistant pp65. We report that HCMV expressing a protein-S-nitrosylation-deficient pp65 is resistant to the activation of cGAS in the infection of primary dermal fibroblasts. Our work suggests that nitrosylation of viral proteins may serve as a broadly neutralizing mechanism in HCMV infection.</p><p><strong>Importance: </strong>Post-translational modifications (PTM) are utilized by host cells to limit an invading pathogen's ability to establish a productive infection. A potent PTM, called protein-S-nitrosylation, has anti-bacterial and anti-viral properties. Increasing protein-S-nitrosylation with the addition of nitric oxide donor compounds reduced HCMV replication in fibroblasts and epithelial cells. We previously reported that protein-S-nitrosylation of HCMV pp71 limits its ability to inhibit STING. Herein, we report that the protein-S-nitrosylation of HCMV pp65 impacts its ability to limit cGAS activity, an additional protein important in regulating interferon response. Therapeutically, patients provided nitric oxide by inhalation reduced viral replication in coronavirus disease 2019, influenza, and even impacted bacterial growth within patients' lungs. It is thought that an increase in free nitric oxide increases the frequency of nitrosylated proteins. Understanding how protein-S-nitrosylation regulates a common DNA virus like HCMV will provide insights into the development of broadly neutralizing therapeutics in drug-resistant viral infections.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0048125"},"PeriodicalIF":4.0,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143969275","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mysteries of adenovirus packaging.","authors":"Matthew Charman, Matthew D Weitzman","doi":"10.1128/jvi.00180-25","DOIUrl":"https://doi.org/10.1128/jvi.00180-25","url":null,"abstract":"<p><p>It is conventionally held that most DNA viruses package their genomes by one of two fundamental mechanisms: described by the sequential or concurrent models of assembly and packaging. Sequential packaging involves the translocation of a viral genome into a pre-formed capsid, often referred to as the pro-capsid. In contrast, concurrent packaging does not require the assembly of a pro-capsid. Instead, the genome is condensed, and the capsid shell is formed around the genome. The accumulation of empty particles in adenovirus infected cells has led to the assumption that adenovirus packaging may be best described by the sequential model. However, existing models fail to adequately explain all experimental observations, leaving many mysteries of adenovirus genome packaging unresolved. In this review, we describe key findings in adenovirus assembly and packaging, and we discuss them in the context of the competing models of sequential versus concurrent packaging. We discuss recent findings that have redefined our understanding of adenovirus packaging, including the role of viral biomolecular condensates and visualization of viral assembly and packaging <i>in situ</i>. These advances have renewed interest in the concurrent model of packaging. We anticipate that lessons learned from adenovirus packaging will be highly valuable for the advancement of viral vectors and gene-delivery technologies. In reviewing this topic, we hope to stimulate discussion and facilitate future investigation that will ultimately resolve gaps in knowledge and expand our understanding of DNA virus genome packaging.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0018025"},"PeriodicalIF":4.0,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143971198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Engineering iridoviruses: development of reverse genetics and virus rescue systems.","authors":"Daria Vladimirova, Daniela Kunecova, Mariana Nascimento, Ji Yoon Kim, Dusan Kunec, Jakob Trimpert","doi":"10.1128/jvi.01852-24","DOIUrl":"https://doi.org/10.1128/jvi.01852-24","url":null,"abstract":"<p><p>Iridoviruses are a family of large DNA viruses that infect insects and poikilotherm vertebrates, including amphibians, reptiles, and fish. Notably, members of the genus <i>Ranavirus</i> cause mass mortality in fish and amphibians, threatening aquaculture and contributing to global amphibian decline. Despite their omnipresence and impact, key aspects of iridovirus biology remain unknown, largely due to the absence of reverse genetics systems. In this study, we developed, characterized, and utilized a reverse genetics system for frog virus 3 (FV3, <i>Ranavirus rana1</i>), one of the most widely studied iridoviruses. The rescued virus exhibits growth and phenotypic properties identical to those of the parental virus isolate. Furthermore, we established an alternative approach of virus reconstitution from genomic DNA, utilizing a heterologous iridovirus as a helper. This novel approach enables rapid and facile rescue of modified viruses from naked DNA. The reverse genetics and rescue systems described in this study will advance iridovirus research by facilitating efficient genetic modification of the virus genome in yeast or bacteria. This could clear the path to elucidating functions of virus genes and allow a much more detailed understanding of iridovirus biology. Moreover, owing to the promiscuous nature of FV3 with its ability to infect hosts from different classes of animals, the FV3 system has the potential to serve as a platform for the development of modified live vaccines for a variety of fish and amphibian species.IMPORTANCEIridoviruses pose a substantial threat to aquaculture and global amphibian populations, yet research has been hindered by the lack of a reverse genetics system. In this study, we describe the development of the first such system for this virus family. We constructed a synthetic clone of frog virus 3 (FV3) that can be propagated and genetically manipulated in both yeast and bacteria, yielding a virus that has biological properties identical to the parental virus isolate. Furthermore, we developed a novel helper virus-based system for the rescue of FV3 from purified DNA. This system provides an essential tool for advancing our understanding of iridovirus biology and serves as a platform for the development of modified live virus vaccines.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0185224"},"PeriodicalIF":4.0,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144016845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lnc-DARVR/miR-365-1-5p/LAMB1 axis regulates rotavirus replication via the complement C3 pathway.","authors":"Xiaopeng Song, Lida Yao, Yan Li, Jinlan Wang, Chenxing Lu, Jinmei Li, Qingmei Leng, Xianqiong Tang, Xiaoqing Hu, Jinyuan Wu, Rong Chen, Xiaochen Lin, Jun Ye, Xiangjun Kuang, Guangming Zhang, Maosheng Sun, Yan Zhou, Hongjun Li","doi":"10.1128/jvi.02114-24","DOIUrl":"https://doi.org/10.1128/jvi.02114-24","url":null,"abstract":"<p><p>Antiviral effectors and cytokines are critical components of host innate immunity. However, the regulatory mechanisms governing the roles of these molecules in host-virus interactions are still unclear. Although long non-coding RNAs (lncRNAs) have been recognized as key players in various biological processes, their involvement in the complement system of host antiviral defenses remains to be explored. In this study, we discovered a novel, unannotated lncRNA, called DARVR. DARVR was found to be an intergenic lncRNA and inhibited rotavirus (RV) replication in MA104 cells. Mechanistically, we found that complement 3 (C3) was upregulated following RV infection in a LAMB1-dependent manner. However, LAMB1 expression was downregulated by miR-365-1-5p, resulting in the inhibition of the C3-mediated antiviral reaction. However, DARVR functioned as a competing endogenous RNA against miR-365-1-5p, promoting the expression of LAMB1 and thereby enhancing C3 activity and inhibiting RV replication. These results not only provide evidence demonstrating the involvement of lncRNAs in the regulation of RV infection but also highlight the role of complement factors in host innate immunity.</p><p><strong>Importance: </strong>Long non-coding RNAs (lncRNAs) play versatile and critical roles in host-virus interactions, offering significant potential for developing targeted therapies to prevent or treat viral infections. Despite their importance, the involvement of lncRNAs in rotavirus infection remains underexplored. This study identifies a novel lncRNA that enhances complement factor C3 activity through the competing endogenous RNA (ceRNA) mechanism, effectively inhibiting rotavirus replication across different subtypes. These findings underscore the complex molecular interplay regulating complement factor activity during rotavirus infection and provide valuable insights into the host's antiviral mechanisms. This research paves the way for innovative therapeutic strategies targeting lncRNAs and complement factors to combat viral infections more effectively.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0211424"},"PeriodicalIF":4.0,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144031801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular characteristics of the immune escape of coronavirus PEDV under the pressure of vaccine immunity.","authors":"Yunchuan Li, Shanshan Yang, Jiali Qian, Shiyu Liu, Yupeng Li, Xu Song, Qiuxia Cao, Rongli Guo, Yongxiang Zhao, Min Sun, Mi Hu, Jizong Li, Xuehan Zhang, Baochao Fan, Bin Li","doi":"10.1128/jvi.02193-24","DOIUrl":"https://doi.org/10.1128/jvi.02193-24","url":null,"abstract":"<p><p>Coronaviruses have undergone evolutionary changes and mutations in response to the immune pressures exerted by vaccines and environmental factors, resulting in more severe consequences during breakthrough infections. Nevertheless, the specific correlation between the evolutionary mutations of coronaviruses and immune pressures remains ambiguous. Swine coronavirus-porcine epidemic diarrhea virus (PEDV)-has existed for decades. This study utilized <i>in vivo</i> preparation of polyclonal antibodies against the PEDV and identified critical neutralizing epitopes through serial <i>in vitro</i> passaging. Then, the recombinant mutated strains were successfully constructed. <i>In vitro</i> experiments confirmed the ability of the rA1273P strain to escape neutralization by polyclonal antibodies. Both <i>in vitro</i> cell studies and <i>in vivo</i> animal experiments revealed that the strain maintains virulence and pathogenicity while evading antibody pressure post-vaccination. The pathogenicity of the strain while evading immune pressure is comparable to wild-type strains. A comparison of the S protein gene between vaccine strains and clinical strains identified mutations in 1273 amino acid positions in clinical strains. In conclusion, this study identified a novel PEDV S protein neutralizing site under immune pressure through serial passaging, indicating that the 1,273th amino acid position is prone to mutation under prolonged antibody pressure, enhancing the virus's ability to escape hosts. This study offers new insights into the interpretation of coronavirus escape immune pressure and provides technical support for monitoring and predicting the variation and evolution of coronavirus.IMPORTANCECoronaviruses represent an ongoing public health threat because of high variability. Since 2010, the emergence of highly pathogenic porcine epidemic diarrhea virus (PEDV) strains has resulted in significant economic losses to the global pig industry. PEDV undergoes evolution and mutation under external immune pressure, rendering it an increasingly challenging target for prevention and control measures. Here, we prepared the polyclonal antibodies against PEDV and identified a novel neutralization epitope on the S protein (1,273th amino acids) through serial <i>in vitro</i> passaging. Furthermore, our findings indicate that the mutation of A1273P in the S protein did not alter the virulence of the PEDV but significantly enhanced its ability to escape and infect the host <i>in vitro</i> and <i>in vivo</i>. Finally, we found that the 1,273 amino acid position of the S gene has been mutated to varying degrees in clinical PEDV strains. This work provides a specific correlation between the evolutionary mutations of coronaviruses and immune pressures.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0219324"},"PeriodicalIF":4.0,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144000801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stabilized dengue virus 2 envelope subunit vaccine redirects the neutralizing antibody response to all E-domains.","authors":"Devina J Thiono, Demetrios Samaras, Thanh T N Phan, Deanna R Zhu, Ruby P Shah, Izabella Castillo, Lawrence J Forsberg, Lakshmanane Premkumar, Ralph S Baric, Shaomin Tian, Brian Kuhlman, Aravinda M de Silva","doi":"10.1128/jvi.00229-25","DOIUrl":"https://doi.org/10.1128/jvi.00229-25","url":null,"abstract":"<p><p>The four dengue virus (DENV) serotypes cause several hundred million infections annually. Several live-attenuated tetravalent dengue vaccines (LAVs) are at different stages of clinical testing and regulatory approval. A major hurdle faced by the two leading LAVs is uneven replication of vaccine serotypes stimulating a dominant response to one serotype at the expense of the other three, leading to the potential for vaccine antibody (Ab)-enhanced, more severe infections by wild-type (WT) DENV serotypes that fail to replicate in the vaccine. Protein subunit vaccines are a promising alternative since antigen dosing can be precisely controlled. However, DENV envelope (E) protein subunit vaccines have not performed well to date, possibly due to differences between the monomeric structure of soluble E and the E homodimer of the viral surface. Previously, we have combined structure-guided computational and experimental approaches to design and produce DENV2 E antigens that are stable homodimers at 37℃ and stimulate higher levels of neutralizing Abs (NAbs) than the WT E antigen in mice. The goal of this study was to evaluate if DENV2 E homodimers stimulate NAbs that target different epitopes on E protein compared to the WT E monomer. Using DENV4/2 chimeric viruses and Ab depletion methods, we mapped the WT E-elicited NAbs to simple epitopes on domain III of E. In contrast, the stable E homodimer stimulated a more complex response toward all three surface-exposed domains of the E protein. Our findings highlight the impact of DENV2 E oligomeric state on the quality and specificity of DENV NAbs and the promise of DENV E homodimers as subunit vaccines.IMPORTANCEThe ideal dengue virus (DENV) vaccine should elicit a balanced and highly protective immune response against all four DENV serotypes. Current tetravalent live-attenuated DENV vaccines have faced challenges due to uneven replication of vaccine virus strains stimulating a strong immune response to one serotype and weak responses to the other three. Protein subunit vaccines provide novel opportunities to stimulate a balanced response because dosing can be precisely controlled and independent of vaccine virus replication. Here, we compare immune responses elicited by a new DENV serotype 2 protein vaccine designed to match the structure of proteins on the viral surface. We find that proteins designed to match the viral surface stimulate better immune responses targeting multiple sites on the viral surface compared to previous protein vaccines. Our results justify further testing and development of these second-generation DENV protein subunit vaccines.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0022925"},"PeriodicalIF":4.0,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144063859","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genome evolution of Kaposi sarcoma-associated herpesvirus (KSHV).","authors":"Razia Moorad, Alice Peng, Justin Landis, Linda J Pluta, Patricio Cano, Angelica Juarez, Dirk P Dittmer","doi":"10.1128/jvi.01950-24","DOIUrl":"https://doi.org/10.1128/jvi.01950-24","url":null,"abstract":"<p><p>Kaposi sarcoma (KS) is the most common cancer in people living with HIV (PLWH), particularly in sub-Saharan Africa (SSA), where Kaposi sarcoma herpesvirus (KSHV or human herpesvirus 8 [HHV-8]) is endemic. In KSHV endemic areas, the overall survival of KS patients has changed little over the past 20 years. A phylogenetic analysis of available full-length viral genomes (<i>n</i> = 164) identified two different virus lineages that co-circulate in KSHV endemic regions today. Their sequences differ from the GenBank reference sequence and those of common laboratory strains, which originated in the 1990s in the US and Europe. Targeted short-read sequencing accuracy was validated by PacBio-based long-read sequencing to resolve repeats. This analysis identified over 1,000 single nucleotide variants (SNV) in a new 14-member sequence collection from tumor biopsies and blood in Malawi with 127 ± 32 (median ± SD) SNV per genome. Most were private, i.e., specific to one individual's virus. Within each of the two lineages, KSHV continues to evolve over time and across national borders by genetic drift and recombination. Analyses of shared SNVs by AlphaFold2 predicted some changes in the conformation of key viral proteins. These findings may help our understanding of herpesvirus evolution.</p><p><strong>Importance: </strong>To understand viruses, the field needs to know their genetic makeup. To develop mechanistic models, targeted therapies, and vaccines, we need comprehensive and up-to-date sequence information on the viral strains that circulate where the diseases appear today. Our knowledge of Kaposi sarcoma herpesvirus (KSHV) sequence distribution and evolution is behind that of other human herpesviruses and RNA viruses. Here, we add to community knowledge using new technologies and artificial intelligence.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0195024"},"PeriodicalIF":4.0,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144029691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction for Yan et al., \"Molecular Determinants of Hepatitis B and D Virus Entry Restriction in Mouse Sodium Taurocholate Cotransporting Polypeptide\".","authors":"Huan Yan, Bo Peng, Wenhui He, Guocai Zhong, Yonghe Qi, Bijie Ren, Zhenchao Gao, Zhiyi Jing, Mei Song, Guangwei Xu, Jianhua Sui, Wenhui Li","doi":"10.1128/jvi.00445-25","DOIUrl":"https://doi.org/10.1128/jvi.00445-25","url":null,"abstract":"","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0044525"},"PeriodicalIF":4.0,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144029618","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}