Journal of Virology最新文献

{"title":"CypA inhibits respiratory syncytial virus (RSV) replication by suppressing glycolysis through the downregulation of PKM2 expression.","authors":"Jing Zhang, Miao Li, Jing Cheng, Yutong Wang, Cuiqing Ma, Lizheng Yin, Jiachao Wang, Xue Gao, Wenzhang Liang, Lin Wei","doi":"10.1128/jvi.00074-25","DOIUrl":"https://doi.org/10.1128/jvi.00074-25","url":null,"abstract":"<p><p>The \"Warburg effect,\" a type of metabolic reprogramming characterized by enhanced glycolysis even in the presence of oxygen, is frequently observed in tumor cells and has also been detected in cells infected with viruses. Our study demonstrated that respiratory syncytial virus (RSV) infection induced aerobic glycolysis both <i>in vivo</i> and <i>in vitro</i>. By utilizing the glycolysis agonist PS48 or inhibitor 2-DG, we ascertained that RSV can utilize glycolysis to promote its replication. Mechanistically, glycolysis may facilitate RSV replication by negatively regulating the IFNβ response. Additionally, we discovered a host molecule, namely CypA, that could downregulate glycolysis to combat RSV infection. CypA interacted with PKM2, a key enzyme of glycolysis, and reduced its expression. By overexpressing or knocking down CypA, we verified that CypA could inhibit aerobic glycolysis, enhance IFNβ production, and reduce RSV replication. Inhibiting the PPIase activity of CypA resulted in the disappearance of its function, indicating that CypA exerted its effects dependent on PPIase activity. Furthermore, we found that CypA has a synergistic effect with 2-DG and an antagonistic effect with PS48 on the IFNβ response, supporting the notion that CypA regulates IFNβ by inhibiting glycolysis. These results indicate that CypA may serve as a novel host factor in the regulation of glycolysis, the interferon response, and ultimately in resisting RSV infection.</p><p><strong>Importance: </strong>Viruses utilize the host's resources and energy to carry out essential life processes and achieve self-replication. In response, hosts have evolved a range of antagonistic mechanisms. Our study investigates how RSV employs glycolysis to benefit its replication, with a particular focus on the interaction between glycolysis and IFNβ regulation. Additionally, we explore how the host employs CypA to antagonize the virus's utilization of glycolysis, thereby inhibiting RSV replication. Our findings will contribute to the development of effective antiviral therapies targeting CypA.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0007425"},"PeriodicalIF":4.0,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144475772","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":"CD317 functions as a key antiviral factor in human herpesvirus 6 (HHV-6) infection.","authors":"Xianyi Xu, Minmin Song, Xin Zhang, Junli Jia, Shuhua Chen, Hua Xie, Lingyun Li, Jingjing Ma, Huamin Tang","doi":"10.1128/jvi.00841-25","DOIUrl":"https://doi.org/10.1128/jvi.00841-25","url":null,"abstract":"<p><p>CD317, an interferon-stimulated gene, is known for its role in inhibiting the release of various enveloped viruses from infected cells. However, its function can vary, as it also promotes infection in certain contexts, such as with human cytomegalovirus (HCMV). Human herpesvirus 6 (HHV-6) and HCMV are both classified within the β-herpesvirus subfamily. The role of CD317 in HHV-6 infection has not been previously investigated. In this study, we found that (i) HHV-6 infection induces CD317 expression, which in turn restricts HHV-6 infection, (ii) type I interferon stimulation induces CD317 expression, thereby inhibiting HHV-6 infection, (iii) the HHV-6 envelope glycoprotein O (gO) interacts with CD317, leading to gO degradation, and (iv) CD317 is incorporated into HHV-6 virions. This work represents the first report elucidating the role of CD317 in HHV-6 infection and reveals a novel function of gO in this process.</p><p><strong>Importance: </strong>Upon stimulation with type I interferon, hundreds of interferon-stimulated genes (ISGs) are induced to express. For an individual virus, it is crucial to identify and analyze the key ISGs. Here, we discovered that CD317 is one of the key ISGs that restrict HHV-6 infection. While CD317 is well known for its ability to inhibit the release of progeny virions, we have revealed a novel role for CD317 in restricting HHV-6 infection by inhibiting viral entry. Additionally, we found that CD317 interacts with HHV-6 glycoprotein O (gO), a protein of unknown function, leading to the proteasomal degradation of gO. This finding may provide valuable clues for further analysis of gO's function.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0084125"},"PeriodicalIF":4.0,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144475771","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":"Enterovirus C recombination groups: RNA sequence similarity and the viral polymerase underpin sexual replication mechanisms.","authors":"Evan M Okolovitch, Vishnu Govindarajan, Refugio Robles-Sikisaka, Grace Campagnola, Brian J Kempf, Andrew L Routh, Olve B Peersen, David J Barton","doi":"10.1128/jvi.00434-25","DOIUrl":"https://doi.org/10.1128/jvi.00434-25","url":null,"abstract":"<p><p>Enteroviruses frequently recombine with one another in nature; however, it is unclear how viral replication machinery can distinguish between related and unrelated partners during recombination. We hypothesize that viral RNA recombination involves two parental RNA templates, nascent RNA products, and their dynamic interactions with the viral polymerase-a sexual replication strategy. When nascent RNA products move from one parental RNA template to another, RNA sequence similarity may be an important factor underpinning the mechanism and efficiency of recombination. To test this hypothesis, we focused on recombination between two related group C enteroviruses, poliovirus and Coxsackievirus A21 (CVA21), using bioinformatic, biological, and biochemical approaches. Bioinformatic analyses comparing 22 prototypical group C enteroviruses delineated four recombination groups where viruses in each group exhibit high RNA sequence and amino acid similarity in their polymerase genes. ClickSeq and ViReMa methods detect recombinant forms of poliovirus with P3 genes from CVA21, analogous to recombinant circulating vaccine-derived polioviruses (cVDPV). Biochemical assays show that poliovirus and CVA21 polymerases can detect mismatched base pairs as they traverse an extended primer grip surface adjacent to the active site. Mismatched base pairs in the -2 and -3 positions destabilize polymerase elongation complexes, consistent with the predicted role of RNA sequence similarity in recombination. Two subgroup-specific genetic elements, upstream open-reading frames (uORFs) and RNase L competitive inhibitor RNAs (RNase L ciRNAs), reinforce the existence and biological relevance of enterovirus C recombination groups. Altogether, our observations suggest that enterovirus RNA replication machinery can distinguish between related and unrelated partners during recombination.</p><p><strong>Importance: </strong>Viral RNA recombination transforms live-attenuated polioviruses into neurovirulent circulating vaccine-derived polioviruses, complicating the planned eradication of poliovirus. When humans are co-infected with poliovirus and related non-polio enteroviruses, viral replication machinery can produce recombinant viruses. However, who recombines with whom? What factors determine whether two distinct viruses can produce recombinant progeny that are fit for transmission from person to person? In this study, we clarify which viruses recombine with one another in nature and further elucidate the mechanisms by which the viral polymerase distinguishes between related and unrelated RNA templates-a sexual form of replication. Understanding these mechanisms could lead to better strategies for virus control and/or eradication.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0043425"},"PeriodicalIF":4.0,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144475773","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":"The role of Nef in the long-term persistence of the replication-competent HIV reservoir in South African women.","authors":"Sherazaan D Ismail, Shorok Sebaa, Bianca Abrahams, Martha C Nason, Mitchell J Mumby, Jimmy D Dikeakos, Sarah B Joseph, Matthew Moeser, Ronald Swanstrom, Nigel Garrett, Carolyn Williamson, Thomas C Quinn, Melissa-Rose Abrahams, Andrew D Redd","doi":"10.1128/jvi.00217-25","DOIUrl":"10.1128/jvi.00217-25","url":null,"abstract":"<p><p>HIV-1 Nef mediates immune evasion and viral pathogenesis in part through the downregulation of cell surface cluster of differentiation 4 (CD4) and major histocompatibility complex class I (MHC-I) on infected cells. While the Nef function of circulating viral populations found early in infection has been associated with reservoir size in early-treated cohorts, there is limited research on how its activity impacts reservoir size in people initiating treatment during chronic infection. In addition, there is little research on its role in the persistence of viral variants during long-term antiretroviral therapy (ART). Phylogenetically distinct <i>nef</i> genes (<i>n</i> = 82) with varying estimated times of reservoir entry were selected from viral outgrowth variants stimulated from the reservoir of South African women living with HIV who initiated ART during chronic infection (<i>n</i> = 16). These <i>nef</i> genes were synthesized and used in a pseudovirus infection assay that measures CD4 and MHC-I downregulation via flow cytometry. Downregulation measures were compared to the size of the replication-competent viral reservoir (RC-VR), estimated by quantitative viral outgrowth assay at 5 years after treatment initiation, as well as proviral survival time. Maximum Nef-mediated MHC-I downregulation was significantly associated with RC-VR size (<i>P</i> = 0.034), but this association was not observed for CD4 downregulation. Conversely, we did not find a consistent association between intraparticipant MHC-I or CD4 downregulation and the variant timing of entry into the reservoir. These data support a role for Nef-mediated MHC-I downregulation in determining RC-VR size, but more work is needed to determine Nef's role in the survival of individual viral variants over time.IMPORTANCERational design of HIV cure interventions requires an understanding of the viral determinants of reservoir dynamics. For an equitable cure, it needs to be broadly applicable. While African women bear the greatest burden of HIV globally, most cure research has focused on men in the global North. Our study aims to elucidate viral determinants of HIV persistence in South African women on antiretroviral therapy. We hypothesized that the HIV protein Nef subverts immune clearance of infected cells by downregulating surface levels of two cellular proteins, CD4 and MHC-I. We compared this downregulation capacity with reservoir size and variant survival in the reservoir. We found a positive association between an individual's reservoir size and MHC-I downregulation, but there was little evidence for a survival benefit with stronger MHC-I reduction. These data support earlier work and suggest that Nef's interaction with MHC-I may be a target to restrict the latent reservoir in cure strategies.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0021725"},"PeriodicalIF":4.0,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144475775","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":"METTL3 regulates PRRSV replication by suppressing interferon beta through autophagy-mediated IKKε degradation.","authors":"Yunyun Zhai, Lucai Wang, Lijie Lv, Xuyang Zhao, Mengjie Li, Jiajing Tian, Xiangqi Qiu, Lulu Yao, Wenhui Zhu, Yunzhe Kang, Angke Zhang, Guoqing Zhuang, Aijun Sun","doi":"10.1128/jvi.00098-25","DOIUrl":"https://doi.org/10.1128/jvi.00098-25","url":null,"abstract":"<p><p>Methyltransferase-like-3 (METTL3)-mediated N6-methyladenosine (m⁶A) modification of messenger RNAs plays a pivotal role in regulating innate immune responses, either promoting or combating virus replication. However, the biological function of METTL3 during porcine reproductive and respiratory syndrome virus (PRRSV) infection remains unclear. In this study, we found that PRRSV infection reprograms m⁶A modifications in cellular transcripts, enhances METTL3 expression, and alters its subcellular distribution. Intriguingly, METTL3 overexpression facilitates PRRSV replication, whereas its deficiency suppresses it, primarily through the negative regulation of type I interferon (IFN-I) production. Further investigation revealed that METTL3 interacts with and promotes the degradation of IκB kinase-ε (IKKε) during PRRSV infection. Mechanistically, METTL3-mediated m⁶A modification of SQSTM1 (sequestosome 1) enhances <i>SQSTM1</i> messenger RNA (mRNA) expression, increasing autophagy levels. Moreover, METTL3 facilitates the formation of K63-linked ubiquitin chains on IKKε, targeting it for degradation via SQSTM1-dependent selective autophagy. Collectively, our findings unveil a novel mechanism whereby METTL3 facilitates PRRSV replication by suppressing antiviral innate immunity, thereby offering potential targets for antiviral therapy.IMPORTANCEPorcine reproductive and respiratory syndrome (PRRS), induced by the porcine reproductive and respiratory syndrome virus (PRRSV), poses a highly contagious threat to the global swine industry, leading to substantial economic losses. The genetic variability and immune evasion capabilities of PRRSV complicate the development of effective vaccines and control strategies. Thus, a comprehensive understanding of PRRSV's immune evasion mechanisms is imperative. In this study, we reveal that METTL3 plays a pivotal role in PRRSV's evasion of interferon (IFN) immunity. Specifically, METTL3 targets IKKε, inducing its autophagy degradation and subsequently inhibiting the expression of interferon beta 1 (IFNB1). Furthermore, PRRSV infection alters the N6-methyladenosine (m⁶A) modification of various host genes, with notable changes observed in the m⁶A modification and transcriptional levels of SQSTM1, which are regulated by METTL3. This regulation is crucial for SQSTM1-mediated autophagy degradation of IKKε. Our findings offer novel insights into the mechanisms underlying host protein involvement in PRRSV's immune evasion.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0009825"},"PeriodicalIF":4.0,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144475774","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":"The SHFV nsp2 and nucleocapsid proteins recruit G3BP1 to sites of viral replication, but stress granules are not induced by the infection.","authors":"Ayisha A Lavender, Oreoluwa Solanke, Hsin-Yao Tang, Hannah E Peck, Daryll Vanover, Philip J Santangelo, Margo A Brinton","doi":"10.1128/jvi.00794-25","DOIUrl":"https://doi.org/10.1128/jvi.00794-25","url":null,"abstract":"<p><p>Stress granules (SGs) are dynamic, cytoplasmic foci that form in response to environmental stresses, including viral infections, and function to restore cellular homeostasis by regulating mRNA translation, storage, and decay. To inhibit SG formation and subvert their antiviral effects, viruses from diverse families sequester or cleave G3BP1, the key SG nucleating protein. We found that an infection with simian hemorrhagic fever virus (SHFV), a member of the family <i>Arteriviridae</i>, does not induce the formation of <i>bona fide</i> SGs despite inducing phosphorylation of PKR and eIF2α. The SG proteins, G3BP1, G3BP2, TIA-1, Caprin-1, and USP10, but not the translation initiation proteins, eIF3A, eIF4G, and small ribosomal protein S6 (rpS6), were redistributed into foci located in the same intracellular region as the viral dsRNA foci. However, SGs could be induced in infected cells by exogenous inducers. LC-MS/MS analysis of the proteins co-immunoprecipitating with endogenous G3BP1 from SHFV-infected cell lysates detected multiple viral replication/transcription complex proteins. Interaction between G3BP1 and the nsp2 and N proteins of SHFV was observed in reciprocal co-immunoprecipitation assays, and colocalization was detected by IFA. A conserved FGAP motif in nsp2 and a FAEP motif in the N protein were shown to be required for interaction with G3BP1. We also detected G3BP cleavage products in the SHFV-infected cell lysates and hypothesize that cleavage is mediated by a viral protease. These findings suggest that SG formation is not induced by an SHFV infection due to recruitment of G3BP to sites of viral replication and cleavage of G3BP by viral proteins.IMPORTANCEEukaryotic cells shut down translation by assembling stress granules (SGs) in response to environmental stresses, including viral infections. Viruses require cellular translation machinery for protein synthesis and have developed mechanisms to subvert SG assembly. Simian hemorrhagic fever virus (SHFV), a simian arterivirus, causes asymptomatic infections in African cercopithecoid monkeys but fatal hemorrhagic fever disease in Asian macaques. Even though intracellular production of SHFV RNA activates the stress sensor, PKR, SGs are not induced. G3BP1, the main nucleating protein of SGs, is recruited to foci located near viral replication complexes through interaction with the viral proteins nsp2 and N. An FGAP motif in nsp2 and an FAEP motif in the N protein are required for interaction with G3BP1. Cleavage of G3BP1 was identified as an additional mechanism of viral counteraction of SG formation.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0079425"},"PeriodicalIF":4.0,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144475776","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":"Zika virus non-structural protein NS2A mediated endoplasmic reticulum stress through interacting with Sarco/endoplasmic reticulum Ca²⁺-ATPase 2.","authors":"Shan Wang, Shanshan Tang, Yuxin Zhou, Qifei An, Mengxing Du, Xiujuan Yang, Peng Zou, Li Tang, Yufeng Yu","doi":"10.1128/jvi.00405-25","DOIUrl":"https://doi.org/10.1128/jvi.00405-25","url":null,"abstract":"<p><p>Zika virus (ZIKV) infection of neuronal cells leads to endoplasmic reticulum (ER) stress, which is one of the key causes of neuronal damage. However, how ZIKV mediates ER stress has not been fully understood. Here, we observed that ZIKV infection of astrocytes elevated Sarco/endoplasmic reticulum Ca²⁺-ATPase (SERCA) expression, increased intracellular Ca²⁺ concentration, and upregulated ER stress-related genes. SERCA2 was identified to regulate Ca²⁺ homeostasis and ER stress during ZIKV infection through both knockdown and overexpression of SERCA2 in astrocytes. Furthermore, ZIKV NS2A interacted with SERCA2 and increased the expression of SERCA2, disrupted Ca²⁺ homeostasis, and induced ER stress in astrocytes. After the knockdown of SERCA2 expression, Ca²⁺ homeostasis and ER stress were significantly mitigated in astrocytes expressing NS2A. Additionally, pTMS1-2 and pTMS4-5 of NS2A interacted with SERCA2 and regulated Ca²⁺ homeostasis and ER stress. ZIKV infection of the brains of BALB/c neonatal mice also elevated expression of SERCA2 and ER stress-related genes. Furthermore, SERCA2 expression facilitated ZIKV replication. These results suggested that ZIKV NS2A mediates ER stress through its interaction with SERCA2, providing new insights into the pathogenic mechanism of ZIKV and the development of anti-ZIKV therapies.</p><p><strong>Importance: </strong>Zika virus (ZIKV) infection induces intracellular Ca²⁺ imbalance and endoplasmic reticulum (ER) stress. However, the molecular mechanisms involved in it remain unknown. Here we reported, for the first time, that ZIKV infection increased the expression of Sarco/endoplasmic reticulum Ca²⁺-ATPase 2 (SERCA2), which plays a crucial role in regulating Ca²⁺ homeostasis and ER stress. Furthermore, ZIKV NS2A was found to interact with SERCA2, contributing to the regulation of Ca²⁺ homeostasis and ER stress during ZIKV infection. And ZIKV NS2A pTMS1-pTMS2 and pTMS4-pTMS5 were the specific sites that interacted with SERCA2. These findings elucidate that the interaction between NS2A and SERCA2 is responsible for the regulation of the upstream signaling pathway of ER stress mediated by ZIKV infection. Additionally, the expression of SERCA2 promoted ZIKV proliferation, indicating that SERCA2 may serve as a potential target for anti-ZIKV therapies.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0040525"},"PeriodicalIF":4.0,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144475777","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 mechanism of potently neutralizing human monoclonal antibodies against severe fever with thrombocytopenia virus infection.","authors":"Chuansong Quan, Kaixiao Nie, Dezhen Ma, Chao Su, Lianfeng Li, Wenjun Zheng, Chunhong Yin, Yiwen Wang, Peipei Yang, Dingkun Peng, Xin Liu, Weiwei Li, Weixiao Liu, Chao Shan, Jie Zheng, Di Liu, Hong Zhang, Michael J Carr, George F Gao, Jianxun Qi, Weifeng Shi","doi":"10.1128/jvi.00533-25","DOIUrl":"10.1128/jvi.00533-25","url":null,"abstract":"<p><p>Although severe fever with thrombocytopenia syndrome (SFTS) was first described in China in 2009, the case fatality rate remains >40% among patients with multi-organ failure. To date, no antivirals specifically targeting SFTSV have been approved. We obtained several monoclonal antibodies (mAbs) from SFTS survivors by single-cell RNA-seq. Neutralization and animal experiments were applied to assess the effects of these mAbs <i>in vitro</i> and <i>in vivo</i>, and co-crystal structures with SFTSV-Gn glycoproteins were determined by X-ray crystallography. The mAbs SD4, SD12, and SD22 targeted the SFTSV-Gn with high neutralizing activities, and, remarkably, SD4 and SD22 exhibited <i>K_D</i> values in the range of 32-83 pM for different viral genotypes. Notably, a single administration (20 mg/kg) of SD4 and SD22 showed 100% protection in mice at day 3 post-inoculation (dpi). Importantly, SD4 also provided 60% protection at a lower dose (0.3 mg/kg) when administered at 3 dpi. The crystallographic structures of SD4, SD22, and SD12 with Gn were determined at 3.3 Å, 2.8 Å, and 2.4 Å, respectively, which revealed that they recognized a conserved antigenic epitope around the hexon wellhead edge. These human-derived mAbs have significant therapeutic potential for severe SFTS cases and provide a basis for rational antibody-based vaccine designs and clinical trials.</p><p><strong>Importance: </strong>The incidence of severe fever with thrombocytopenia syndrome (SFTS) has been increasing in Asia in recent years; however, no specific antiviral agents have been approved to date. Herein, we report a panel of anti-SFTSV Gn monoclonal antibodies (mAbs) with excellent neutralizing capacities and remarkable therapeutic potential <i>in vitro</i> and <i>in vivo</i> in a mouse model. In addition, crystallographic structures of mAbs complexed with Gn were resolved with atomic resolution (2.4 Å-3.3 Å), revealing a conserved antigenic epitope near the hexon wellhead edge. In sum, the neutralizing antibodies reported in the present study have significant therapeutic potential, paving the way for effective treatment of severe SFTS patients.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0053325"},"PeriodicalIF":4.0,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144333428","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":"Diversity and evolutionary history of RNA viruses among different horseshoe crab species.","authors":"Yu-Hua Qi, Zhuang-Xin Ye, Ke-Hui Feng, Xiao-Wan Ma, Chuan-Xi Zhang, Meng-Hong Hu, Mang Shi, Jian-Ping Chen, Jun-Min Li","doi":"10.1128/jvi.00164-25","DOIUrl":"10.1128/jvi.00164-25","url":null,"abstract":"<p><p>Horseshoe crabs (Xiphosura: Limulidae) are the sole surviving species of the class Merostomata, with only four extant species remaining today. Recent advances in metagenomic next-generation sequencing have unveiled a vast diversity of RNA viruses and non-retroviral endogenous RNA viral elements (nrEVEs) in invertebrates. This raises intriguing questions about the RNA virome and nrEVEs in horseshoe crabs as \"living fossils,\" potentially offering insights into the evolutionary relationships between RNA viruses and these ancient organisms. In this study, 22 novel RNA viruses were identified across the four horseshoe crab species by screening 117 data sets, including picornaviruses, totiviruses, a flavivirus, a rhabdovirus, as well as a plant-associated tombusvirus and a fungi-associated narnavirus. Additionally, 20 nrEVEs were identified in the genomes of the four horseshoe crab species (hcEVEs), with most sharing homology with the viral family <i>Chuviridae</i> (<i>N</i> = 11), supporting the hypothesis that modern negative-sense RNA viruses may trace their origins to ancient oceanic chuviruses. A time-scaled phylogenetic tree based on hcEVEs suggests that at least two independent ancient chuvirus infections and genome integration events occurred in the common ancestor of horseshoe crab species. Interestingly, transcriptional analyses indicated that hcEVE-containing transcripts display typical exon-intron structures in the three Asian horseshoe crab species, suggesting that these hcEVEs may have been co-opted by horseshoe crabs during coevolution. These findings advance our understanding of the RNA viruses associated with horseshoe crabs and shed light on the potential role of RNA viruses in shaping the evolutionary history of this \"living fossil\" arthropod host.IMPORTANCERecent studies have discovered abundant RNA viruses in invertebrates, revealing that viral genomes may integrate into host genomes, creating a genetic record of past infections. In this study, we explored the evolutionary relationship between RNA viruses and the four extant horseshoe crab species-the last representatives of the class Merostomata, often termed \"living fossils\"-by analyzing viral sequences embedded in their genomes. The presence of chuvirus-like sequences in the genomes of these horseshoe crabs suggests that modern negative-sense RNA viruses may trace their origins back to ancient chuviruses from the ocean. Furthermore, we identified at least two independent ancient integrations of chuviruses in the evolutionary history of horseshoe crabs, with one orthologous gene containing a chuvirus-derived G protein gene/coding sequence potentially inherited from a common ancestor of the three Asian species before their divergence. Our findings contribute to a deeper understanding of the long-term coevolution between RNA viruses and their arthropod hosts.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0016425"},"PeriodicalIF":4.0,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144333426","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":"Efficacy of oncolytic virus in the treatment of intermediate-to-advanced solid tumors: a systematic review and meta-analysis.","authors":"Jin-Zhou Xu, Jian-Xuan Sun, Chen-Qian Liu, Ruo-Yan Pan, Na Zeng, Si-Han Zhang, Ye An, Meng-Yao Xu, Xing-Yu Zhong, Si-Yang Ma, Hao-Dong He, Jia Hu, Shao-Gang Wang, Qi-Dong Xia","doi":"10.1128/jvi.00640-25","DOIUrl":"10.1128/jvi.00640-25","url":null,"abstract":"<p><p>This meta-analysis assessed oncolytic virus therapy's efficacy for intermediate-to-advanced solid tumors. We systematically searched PubMed, Cochrane Library, and Embase databases until March 6, 2025. Our review included 87 studies, involving 5,385 individuals, encompassing 75 clinical trials and 12 retrospective studies. Patient response rates were as follows: complete response (CR) 11%, partial response (PR) 18%, stable disease (SD) 32%, and progressive disease (PD) 32%. The overall response rate (ORR) was 29%, and the durable response rate (DRR) was 39%. Comparing oncolytic virus therapy to alternatives, the odds ratio (OR) for overall response was 1.62, and the hazard ratio (HR) for overall survival (OS) was 0.86. This analysis emphasizes the effectiveness of oncolytic virus therapy for intermediate-to-advanced solid tumors, highlighting its promise as a treatment option. These findings offer vital insights into cancer therapy researchers and practitioners.IMPORTANCEAlthough previous meta-analyses on this topic have been published, our research addresses the limitations of previous studies by including missed and newly published studies, updating the results, and conducting extensive subgroup analyses. Our study fills a gap in the literature by providing a comprehensive evaluation of the therapeutic potential of oncolytic viruses for solid tumors.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0064025"},"PeriodicalIF":4.0,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144333427","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}