Journal of Medical Virology最新文献

{"title":"SARS-CoV-2 Membrane Protein Induces MARCHF1/GPX4-Mediated Ferroptosis by Promoting Lipid Accumulation","authors":"Pei Sun,&nbsp;Qian Liu,&nbsp;Shuofeng Yuan,&nbsp;Xin-Tao Wang,&nbsp;Ye Qiu,&nbsp;Xing-Yi Ge","doi":"10.1002/jmv.70328","DOIUrl":"https://doi.org/10.1002/jmv.70328","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 <p>The membrane protein (M), a key structural protein of SARS-CoV-2 that regulates virus assembly and morphogenesis, is involved in the pathological processes of multiple organ damage and metabolic disorders. This study aims to elucidate the mechanisms of M-mediated host ferroptosis and lipid accumulation during SARS-CoV-2 infection. Here, we detected that M protein enhances cellular sensitivity to ferroptosis. Additionally, we uncovered the pivotal role of perilipin-2 and sterol regulatory element-binding protein 1 in M-induced lipid accumulation. Xanthohumol, a cost-effective and orally available diacylglycerol acyltransferase inhibitor, alleviated triglyceride and total cholesterol accumulation, thereby counteracting the M-induced ferroptosis. Furthermore, we identified that the mitochondrial import inner membrane translocase subunit TIM23 and the mitochondrial import receptor subunit TOM20 homolog contribute to M-induced mitochondrial dysfunction. Notably, inhibiting lipid synthesis effectively reduced mitochondrial reactive oxygen species and transmembrane potential, indicating a cross-talk between lipid and ferro metabolic pathways. Mechanistically, glutathione peroxidase 4 (GPX4) interacts with SARS-CoV-2 M, leading to its subsequent degradation by the Membrane Associated Ring-CH-Type Finger 1 (MARCHF1) ubiquitin ligase. M-GPX4 interaction occurs at the R72 residue, which may represent a potential therapeutic target against SARS-CoV-2 infection. M modulates lipid accumulation and further impairs mitochondrial functions, ultimately resulting in ferroptosis through MARCHF1-GPX4 axis. Disrupting host-virus interactions along this pathway may provide a therapeutic strategy for SARS-CoV-2 infection.</p>\u0000 </section>\u0000 </div>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 4","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143778293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unveiling the Dynamics of SARS-CoV-2 Gamma and Delta Waves in Paraná, Brazil – Delta Displacing a Persistent Gamma Through Alternative Routes of Dispersal","authors":"Emanuele Gustani-Buss,&nbsp;Carlos Eduardo Buss,&nbsp;Carlos Alberto Oliveira de Biagi,&nbsp;Isabela Medeiros de Oliveira,&nbsp;Kamila Chagas Peronni,&nbsp;Glauco Akelinghton Freire Vitiello,&nbsp;Bárbara Luisa Fermino,&nbsp;Fernanda Ivanski,&nbsp;Bárbara Mendes Paz Chao,&nbsp;Felipe Francisco Bondan Tuon,&nbsp;Franciele Ani Caovilla Follador,&nbsp;Leia Carolina Lucio,&nbsp;Lirane Elize Defante Ferreto,&nbsp;Marcos Pillegi,&nbsp;Jeane Eliete Laguila Visentainer,&nbsp;Marcia Edilaine Lopes Consolaro,&nbsp;Maria Leandra Terêncio,&nbsp;Dennis Armando Bertolini,&nbsp;Alex Sandro Jorge,&nbsp;Jaime Luis Lopes Rocha,&nbsp;Bruno Zagonel Piovesan,&nbsp;Irina Nastassja Riediger,&nbsp;Diogo Muller Lacerda,&nbsp;Angélica Regina Cappellari,&nbsp;Marco Antonio Largura,&nbsp;Álvaro Largura,&nbsp;Patrik André Barcaro,&nbsp;Vitoria Caroline Tomacheski Schultz Bertol,&nbsp;Marcos Aurélio Pelegrina,&nbsp;Glauco Nonose Negrão,&nbsp;Carla Luiza da Silva,&nbsp;Daniela Frizon Alfieri,&nbsp;Tony Vinicius Moreira Sampaio,&nbsp;Andrea Name Colado Simao,&nbsp;Emerson Carraro,&nbsp;Wilson Araújo Silva Jr.,&nbsp;Phillippe Lemey,&nbsp;David Livingstone Alves Figueiredo","doi":"10.1002/jmv.70318","DOIUrl":"https://doi.org/10.1002/jmv.70318","url":null,"abstract":"<p>The Gamma and Delta variants of concern (VOCs) of SARS-CoV-2 drove the second and third wave in Brazil and significantly intensified the number of cases and deaths. In this study, we investigate the timeline and origins of the Gamma and Delta variants using a spatiotemporal analysis based on 1508 genomes collected between March and September 2021 from health administrative regions in Paraná state, Brazil. Our findings indicate that community transmission of Gamma-P.1 began in late 2020, with substantial contributions from the Northeast and North regions. In contrast, our analysis of the Delta-AY.101 genomes underscored the crucial role of Paraná in national-level transmission dynamics beginning in late March 2021. At a local level, the movement estimates inferred from the monophyletic clades showed that the Curitiba health region was the primary source for Gamma-P.1, with a substantial contribution from Londrina. This health-region also emerged as an important hub for Delta-AY.101. Our phylogeographical GLM analysis demonstrates that air travel fluxes and population size at the origin of locations were the strongest predictors of shaping SARS-CoV-2 dispersal dynamics within Paraná. In addition, viral load analysis suggests that Gamma-P.1 and Delta-AY.101 may have maintained a similarly high transmissibility potential throughout the evaluated months, providing insights into the prolonged co-circulation dynamics. Our study underscores the relevance of understanding SARS-CoV-2 introductions and regional circulation contributions at the country level to enhance public health preparedness and strengthen local surveillance programs.</p>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 4","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jmv.70318","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143778292","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}

{"title":"H3K27-me3 Inhibition Induces YTHDF2-Mediated Decay of m6A-Marked Severe Acute Respiratory Syndrome Coronavirus 2 Transcripts","authors":"Ram Kumar,&nbsp;Assim Verma,&nbsp;Himanshu Kamboj,&nbsp;Tarun K. Bhattacharya,&nbsp;Sanjay Barua,&nbsp;Bhupendra N. Tripathi,&nbsp;Shalini Sharma,&nbsp;Naveen Kumar","doi":"10.1002/jmv.70332","DOIUrl":"https://doi.org/10.1002/jmv.70332","url":null,"abstract":"<div>\u0000 \u0000 <p>Emerging evidence highlights the role of epigenetic modification in virus infection. In this study, inhibition of H3K27-methylation (H3K27-me3) by UNC1999 (H3K27-methyltransferase inhibitor) was demonstrated to inhibit SARS-CoV-2 replication, as evidenced by reduced levels of viral RNA/protein. The m6A modifications of SARS-CoV-2 RNA were predominantly present on the 3ʹ end, particularly the “N” gene. The methylated RNA immunoprecipitation (MeRIP) and western-blot analysis revealed a negative correlation between levels of cellular H3K27-me3 and m6A-modifications on the SARS-CoV-2 “N” gene. Moreover, m6A-modifications of the SARS-CoV-2 “N” gene were shown to promote the recruitment of YTHDF2, which eventually resulted in decay of the viral transcripts. The application of the H3K27-demethyltransferase or KDM6A/B inhibitor GSK-J4 can restore H3K27-me3 levels and mitigating the decay of viral mRNA in UNC1999-treated SARS-CoV-2-infected cells. Furthermore, long-term sequential passage (P = 50) of the virus in the presence of UNC1999 did not yield any UNC1999-resistant SARS-CoV-2 mutants. In conclusion, by integrating transcriptomics, molecular virology and functional analyses, we for the first time demonstrated that inhibition of H3K27-me3 induces m6A-mediated decay of SARS-CoV-2 transcripts, highlighting UNC1999 as novel antiviral candidate against SARS-CoV-2.</p>\u0000 </div>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 4","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143770440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Myeloid-Driven Immune Suppression Subverts Neutralizing Antibodies and T Cell Immunity in Severe COVID-19","authors":"Cong Lai,&nbsp;Su Lu,&nbsp;Yilin Yang,&nbsp;Xiaoyu You,&nbsp;Feixiang Xu,&nbsp;Xinran Deng,&nbsp;Lulu Lan,&nbsp;Yuesheng Guo,&nbsp;Zhongshu Kuang,&nbsp;Yue Luo,&nbsp;Li Yuan,&nbsp;Lu Meng,&nbsp;Xueling Wu,&nbsp;Zhenju Song,&nbsp;Ning Jiang","doi":"10.1002/jmv.70335","DOIUrl":"https://doi.org/10.1002/jmv.70335","url":null,"abstract":"<p>The objective of this study was to better understand immune failure mechanisms during <i>severe acute respiratory syndrome coronavirus 2</i>, SARS-CoV-2 infection, which are critical for developing targeted vaccines and effective treatments. We collected 34 cases representing different disease severities and performed high-quality single-cell TCR/BCR sequencing to analyze the peripheral immune cell profiles. Additionally, we assessed antibody-neutralizing activity through in vitro experiments. Our integrated multiomics analysis uncovers a profound immune paradox in severe COVID-19: hyperinflammation coexists with immunosuppression, driven by distinct yet interconnected dysregulatory mechanisms. Severe patients develop robust humoral immunity, evidenced by clonally expanded plasma cells producing neutralizing antibodies (e.g., IGHG1-dominated responses) and antigen-specific T cell activation. However, these protective responses are counteracted by myeloid-driven immunosuppression, particularly <i>CD14</i>+ <i>HMGB2+</i> monocytes exhibiting metabolic reprogramming and HLA-DR downregulation, coupled with progressive T cell exhaustion characterized by IFN-γ/TNF-α hyperactivation and impaired antigen presentation. Importantly, prolonged viral persistence in severe cases arises from a failure to coordinate humoral and cellular immunity—antibody-mediated neutralization cannot compensate for defective cytotoxic T cell function and monocyte-mediated immune suppression. These findings highlight the necessity for therapeutic strategies that simultaneously enhance antibody effector functions (e.g., Fc optimization), restore exhausted T cells, and reverse myeloid suppression. They also highlight the importance of vaccines designed to elicit balanced B cell memory and durable T cell responses, which are critical to preventing severe disease progression. By addressing the dual challenges of hyperinflammation and immunosuppression, such approaches could restore immune coordination and improve outcomes in severe COVID-19.</p>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 4","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jmv.70335","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143770185","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}

{"title":"Usefulness of Saliva Samples in the Diagnosis of Monkeypox: Insights From Argentina","authors":"Alicia Lucero,&nbsp;Cristina Videla,&nbsp;Pablo Bonvehi,&nbsp;Natalia Echegoyen,&nbsp;Antonella Martelli,&nbsp;Lucas Amaya,&nbsp;Patricia Baré,&nbsp;Diego M. Flichman,&nbsp;Alfredo P. Martínez,&nbsp;Federico A. Di Lello","doi":"10.1002/jmv.70333","DOIUrl":"https://doi.org/10.1002/jmv.70333","url":null,"abstract":"","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 4","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143762049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expanding Horizons: Mainland China's First Male HPV Vaccine Approval and Its Global Implications","authors":"Wei Mao,&nbsp;Daiwen Xing,&nbsp;Yifei Zhong,&nbsp;Yan Wang,&nbsp;Kunyu Wang,&nbsp;Hang Yi","doi":"10.1002/jmv.70334","DOIUrl":"https://doi.org/10.1002/jmv.70334","url":null,"abstract":"","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 4","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143761991","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Age-Stratified Treg Responses During Viral Infections of the Central Nervous System: A Literature Review","authors":"Vivek R. Singh,&nbsp;Lauren A. O'Donnell","doi":"10.1002/jmv.70315","DOIUrl":"https://doi.org/10.1002/jmv.70315","url":null,"abstract":"<p>Regulatory T cells (Tregs) play a vital role in limiting inflammation and resolving the immune response after a viral infection. Within the central nervous system (CNS), Tregs are especially important for the protection of neurons, which have limited regenerative capacity, and the preservation of myelin sheaths, which support neuronal function and survival. Nevertheless, viral infections of the CNS often result in enduring neurological dysfunction, especially in more vulnerable age groups such as newborns and the elderly. Although it is appreciated that Treg activity changes with age, it is unclear how these age-dependent changes impact viral CNS infections. In this review, we explore Treg development over the life of the host and discuss evidence for age-dependent Treg responses to peripheral viral infections. We also discuss the CNS-specific roles of Tregs, where both immunomodulatory and neuroprotective functions can contribute to preservation of brain cells. Finally, we examine the current evidence for Treg activity in neurotropic infections in the context of age, and highlight gaps in our understanding of Treg function in younger and older hosts. Overall, a better understanding of age-dependent Treg activity in the CNS may reveal opportunities for therapeutic interventions tailored to the most vulnerable ages.</p>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 4","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jmv.70315","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143762108","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}

{"title":"Papaverine Targets STAT Signaling: A Dual-Action Therapy Option Against SARS-CoV-2","authors":"Philipp Reus,&nbsp;Emma Torbica,&nbsp;Tamara Rothenburger,&nbsp;Marco Bechtel,&nbsp;Joshua Kandler,&nbsp;Sandra Ciesek,&nbsp;Philip Gribbon,&nbsp;Aimo Kannt,&nbsp;Jindrich Cinatl,&nbsp;Denisa Bojkova","doi":"10.1002/jmv.70319","DOIUrl":"https://doi.org/10.1002/jmv.70319","url":null,"abstract":"<p>Papaverine (PV) has been previously identified as a promising candidate in SARS-CoV-2 repurposing screens. In this study, we further investigated both its antiviral and immunomodulatory properties. PV displayed antiviral efficacy against SARS-CoV-2 and influenza A viruses H1N1 and H5N1 in single infection as well as in co-infection. We demonstrated PV's activity against various SARS-CoV-2 variants and identified its action at the post-entry stage of the viral life cycle. Notably, treatment of air-liquid interface (ALI) cultures of primary bronchial epithelial cells with PV significantly inhibited SARS-CoV-2 levels. Additionally, PV was found to attenuate interferon (IFN) signaling independently of viral infection. Mechanistically, PV decreased the activation of the IFN-stimulated response element following stimulation with all three IFN types by suppressing STAT1 and STAT2 phosphorylation and nuclear translocation. Furthermore, the combination of PV with approved COVID-19 therapeutics molnupiravir and remdesivir demonstrated synergistic effects. Given its immunomodulatory effects and clinical availability, PV shows promising potential as a component for combination therapy against COVID-19.</p>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 4","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jmv.70319","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143749298","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}

{"title":"The Burden of HPV Infections and HPV-Related Diseases Among People With HIV: A Systematic Literature Review","authors":"Bekana K. Tadese,&nbsp;Xuedan You,&nbsp;Tidiane Ndao,&nbsp;Joseph E. Tota,&nbsp;Ya-Ting Chen,&nbsp;Alisa Chowdhary,&nbsp;Jia Pan,&nbsp;Ana C. Costa,&nbsp;Nelly Mugo","doi":"10.1002/jmv.70274","DOIUrl":"https://doi.org/10.1002/jmv.70274","url":null,"abstract":"<p>Human papillomavirus (HPV) is associated with a significant global burden of precancerous lesions and cancer. People with HIV (PWH) are at higher risk of HPV infection and HPV-related diseases. This systematic review was conducted to synthesize data on the burden of HPV infection and HPV-related diseases among PWH. Studies published between January 2018–June 2023 were sourced from databases and conferences. Included were 221 publications containing epidemiological data on HPV infections and the clinical burden of HPV-related diseases among PWH. The burden varied by geographical region, age, sex, and sexual orientation. Compared to people without HIV (PWoH), PWH had higher prevalence and incidence of HPV infection and HPV-related diseases. Among PWH, the prevalence of anal HPV infection ranged between 44% and 83%; men had a higher prevalence and incidence of anogenital warts than women. The incidence of anal HPV infection was over two-fold greater among transgender women with HIV and men who have sex with men with HIV than among their respective counterparts without HIV. Incident HPV-related anal cancer was up to two-fold higher among PWH than PWoH, and incident cervical cancer was up to six times higher among women with HIV than those without. The most prevalent high-risk (hr) HPV genotypes with HPV-related disease were vaccine genotype HPV16/18/52/58. HPV35 was one of the most prevalent genotypes with anal or cervical HPV infection among PWH of African descent. PWH also have a higher burden of concurrent HPV infections and HPV-related diseases. This study calls for strengthening appropriate HPV vaccine delivery and increasing vaccine uptake among this high-risk group, potentially by integrating HPV vaccination with routine HIV care.</p>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 4","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jmv.70274","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143749301","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}

{"title":"Oral Neisseria gonorrhoeae Promotes KSHV Lytic Replication","authors":"Shu Feng,&nbsp;Wen Fu,&nbsp;Shutong Li,&nbsp;Wayne Yeh,&nbsp;Rosemary She,&nbsp;Charles Brenner,&nbsp;Casey Chen,&nbsp;Pinghui Feng","doi":"10.1002/jmv.70304","DOIUrl":"https://doi.org/10.1002/jmv.70304","url":null,"abstract":"<div>\u0000 \u0000 <p>The human oral cavity contains highly diverse microbes, including bacteria, fungi, and viruses. Human herpesviruses are ubiquitous pathogens, and the oral cavity is conducive to the replication, dissemination, and pathogenesis of human herpesviruses. Herpesviruses are generally pathogenic in immunodeficient individuals, such as AIDS patients and organ transplant recipients. Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiological agent of Kaposi's sarcoma and two types of rare lymphoma, that is, primary effusion lymphoma and multicentric Castleman's disease. Mounting evidence indicates that KSHV viral load positively correlates with ongoing bacterial infection in the oral cavity, suggesting that bacteria potentially stimulate KSHV replication. However, the mechanism by which oral bacteria may promote KSHV lytic replication is poorly understood. In this study, we performed DNA sequencing and 16S ribosomal RNA analysis of saliva samples of AIDS-KS patients. A correlation analysis identified a panel of oral residential bacteria and uncommon ones that paralleled with KSHV viral load. Performing functional assays, we discovered that the sexually transmitted <i>Neisseria gonorrhoeae</i> (<i>N.g.</i>) significantly increased KSHV lytic replication. Increased KSHV lytic replication was evidenced by elevated levels of mRNA and proteins of viral lytic genes. <i>N.g</i>. stimulation increases the expression of RTA that drives viral lytic replication. Metabolomic analysis reveals the synergistic effect of KSHV and <i>N.g</i>. on cellular metabolism, including the glycolysis and purine and pyrimidine synthesis, that likely underpins the elevated KSHV lytic replication. Findings from our study shed light on the molecular detail of bacteria–virus interaction in the oral cavity and provide references to develop an innovative strategy to treat diseases associated with KSHV.</p>\u0000 </div>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 4","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143749302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}