Journal of General Virology最新文献

{"title":"Characterization of human cytomegalovirus infection dynamics in human microglia.","authors":"Marcos Nuevalos Guaita, Tajudeen O Jimoh, Emma B Barrall, Kristina E Atanasoff, Michelle E Ehrlich, Sam Gandy, Estéfani García-Ríos, Pilar Perez Romero, J Andrew Duty, Domenico Tortorella","doi":"10.1099/jgv.0.002096","DOIUrl":"https://doi.org/10.1099/jgv.0.002096","url":null,"abstract":"<p><p>Human cytomegalovirus (HCMV) is a β-herpesvirus that establishes asymptomatic infections in immunocompetent individuals but can cause severe or even life-threatening symptoms in immunocompromised patients. HCMV can replicate in a wide variety of cells through the engagement of diverse cell factors with the viral envelope protein gH/gL/gO (trimer) or gH/gL/UL128/UL130/UL131a (pentamer), allowing for systemic spread within the human host. This study explores HCMV infection tropism and dynamics in human microglia, demonstrating the susceptibility of microglia to both clinical and laboratory HCMV strains, <i>albeit</i> with lower efficacy for the laboratory strain, implying that both the gH/gL-trimer and -pentamer can mediate virus entry in microglia. The importance of the gH/gL pentamer for virus entry was demonstrated by the inhibition of virus infection upon pre-incubation with a soluble neuropilin-2 (NRP-2) entry factor. Further, we demonstrated that HCMV infection can be effectively inhibited by monoclonal antibodies specific for the gH/gL complexes and HCMV hyperimmunoglobulin. Lastly, we report that microglia infection can be prevented by newly characterized chemical entry inhibitors. Altogether, these findings underscore the potential of microglia as valuable models for studying HCMV neurotropism and strategies to block virus infection in cells that can impact neurological disorders.</p>","PeriodicalId":15880,"journal":{"name":"Journal of General Virology","volume":"106 4","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12041478/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144022152","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emergence, migration and spreading of the high pathogenicity avian influenza virus H5NX of the Gs/Gd lineage into America.","authors":"Alejandro J Aranda, Gabriela Aguilar-Tipacamú, Daniel R Perez, Bernardo Bañuelos-Hernandez, George Girgis, Xochitl Hernandez-Velasco, Socorro M Escorcia-Martinez, Inkar Castellanos-Huerta, Victor M Petrone-Garcia","doi":"10.1099/jgv.0.002081","DOIUrl":"https://doi.org/10.1099/jgv.0.002081","url":null,"abstract":"<p><p>The high pathogenicity avian influenza virus H5N1, which first emerged in the winter of 2021, has resulted in multiple outbreaks across the American continent through the summer of 2023 and they continue based on early 2025 records, presenting significant challenges for global health and food security. The viruses causing the outbreaks belong to clade 2.3.4.4b, which are descendants of the lineage A/Goose/Guangdong/1/1996 (Gs/Gd) through genetic reassortments with several low pathogenicity avian influenza viruses present in populations of Anseriformes and Charadriiformes orders. This review addresses these issues by thoroughly analysing available epidemiological databases and specialized literature reviews. This project explores the mechanisms behind the resurgence of the H5N1 virus. It provides a comprehensive overview of the origin, timeline and factors contributing to its prevalence among wild bird populations on the American continent.</p>","PeriodicalId":15880,"journal":{"name":"Journal of General Virology","volume":"106 4","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12032427/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143995225","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent advances in the prevention and treatment of respiratory syncytial virus disease.","authors":"Alexandra Sanchez-Martinez, Tom Moore, Telma Sancheira Freitas, Tami R Benzaken, Shaun O'Hagan, Emma Millar, Helen E Groves, Simon B Drysdale, Lindsay Broadbent","doi":"10.1099/jgv.0.002095","DOIUrl":"10.1099/jgv.0.002095","url":null,"abstract":"<p><p>Respiratory syncytial virus (RSV) is associated with considerable healthcare burden; as such, prevention and treatment of RSV have long been considered a priority. Historic failures in RSV vaccine development had slowed the research field. However, the discovery of the conformational change in the RSV fusion protein (F) has led to considerable advancements in the field. The RSV pharmaceutical landscape has drastically changed in recent years with successful trials of both vaccines and second-generation mAbs leading to licensing and roll-out of these agents in several countries. RSV preventative and therapeutic measures will likely have a significant impact on RSV-related morbidity and mortality. However, there are still gaps in the protection that these immunizations offer that should be addressed. Many unanswered questions about RSV infection dynamics and subsequent disease should be a focus of ongoing research. This review discusses the currently licensed RSV pharmaceuticals and others that have recently progressed to clinical trials.</p>","PeriodicalId":15880,"journal":{"name":"Journal of General Virology","volume":"106 4","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12282282/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143999713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Temperature affects reptarenavirus growth in a permissive host-derived <i>in vitro</i> model.","authors":"Iman Kriještorac Berbić, Simon De Neck, Lorenzo Ressel, Eleni Michalopoulou, Anja Kipar, Jussi Hepojoki, Udo Hetzel, Francesca Baggio","doi":"10.1099/jgv.0.002100","DOIUrl":"https://doi.org/10.1099/jgv.0.002100","url":null,"abstract":"<p><p>Reptarenaviruses cause Boid inclusion body disease (BIBD), a lethal disease primarily affecting captive boa constrictors. The presence of cytoplasmic inclusion bodies (IBs), mainly composed of viral nucleoprotein (NP), in various cell types is characteristic to and a diagnostic criterion of BIBD. We have previously reported that reptarenavirus replication and IB formation are efficient in cell cultures that are maintained at 27-30 °C but not in cells that are kept at 37 °C, the temperature commonly used for mammalian cell cultures. Here, considering the poikilothermic nature of snakes, we studied the ideal temperature(s) for reptarenavirus propagation and the expression of reptarenavirus NP. We incubated <i>Boa constrictor</i> kidney-derived I/1Ki cells at different temperatures (24-36 °C), inoculated them with University of Giessen virus 1 (UGV-1) and monitored both cell growth and virus proliferation. Cell growth was optimal at 30-34 °C and was not significantly affected by UGV-1 infection. Viral RNA release per cell was highest at ambient temperatures between 28 and 32 °C, as determined by qRT-PCR. However, the cells passaged at day 15 post-inoculation released viral RNA at comparable levels even when kept at slightly lower temperatures (24-26 °C). Morphometric analyses undertaken on sections of cell pellets immunostained for reptarenavirus NP found the expression to be most intense at 32 and 34 °C in freshly inoculated cells, and at 28-32 °C in passaged cells. The NP expression positively correlated with the amount of viral RNA released per cell. Our results indicate that the optimal temperature ranges for boid cell growth and reptarenavirus replication (as judged based on antigen expression and RNA release) overlap at about 32 °C. They also suggest that environmental temperature modulation could represent a strategy to impair reptarenavirus replication and, potentially, the spread of reptarenaviruses within and between snake collections.</p>","PeriodicalId":15880,"journal":{"name":"Journal of General Virology","volume":"106 4","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12041477/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144024781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A region of mumps virus nucleoprotein affects defective interfering particle production.","authors":"Jacquline Risalvato, James Zengel, Mark Phillips, Ashley Beavis, Ming Luo, Biao He","doi":"10.1099/jgv.0.002085","DOIUrl":"https://doi.org/10.1099/jgv.0.002085","url":null,"abstract":"<p><p>Mumps virus (MuV) is a negative-sense, single-stranded RNA virus belonging to the family <i>Paramyxoviridae</i>. MuV causes acute infection of the parotid glands, and the infection can result in severe cases of encephalitis, meningitis and deafness in humans. The non-segmented RNA genome of MuV is encapsidated by the nucleocapsid protein (NP), which forms the ribonucleoprotein (RNP) complex that serves as a template for viral RNA synthesis. To make viral genomic RNA accessible to the viral polymerase, a conformational change within NP occurs. Recently, an atomic model of the NP of MuV was developed with cryogenic-electron microscopy (cryo-EM) using PIV5 NP crystal structure as a homology template. To examine NP's structure and function, we performed mutational analysis of MuV NP at region(s) proposed to play a role in accessing viral RNA. The MuV NP mutants containing G185P, A197Q, Q200R and groups denoted as Top (N63G, P139D, A197Q), Tip (P109E, N121G, A124R) and Bottom (G21S, E29T, P43N, R93Q, R304Q) were first tested in a minigenome system. All mutations resulted in reduced reporter gene activities with Q200R and Bottom having the most severe negative effects. Rescuing of recombinant viruses with these mutations was attempted, and only MuV mutants '185 (G185P)', '197 (A197Q)' and 'Top (N63G, P139D, A197A)' were obtained. The 'Top' MuV mutant exhibited normal growth kinetics at low multiplicities of infection (MOIs); however, at high MOIs, the virus had reduced peak litres than low MOIs. Further analysis indicates that production of defective interfering particles (DI particles or DIPs) was enhanced by the mutant virus, indicating that this region, a known alpha-helix hinge region, is important for full-length genome replication, suggesting that it plays a role in maintaining stability of viral RNA-dependent RNA-polymerase on RNP template during MuV viral RNA synthesis. Understanding the production of DI particles will lead to a better understanding of MuV pathogenesis, as well as its replication/transcription process.</p>","PeriodicalId":15880,"journal":{"name":"Journal of General Virology","volume":"106 4","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11992363/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143983536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The loss of both pUL16 and pUL21 in HSV-1-infected cells alters capsid-tegument composition, nuclear membrane architecture, cytoplasmic maturation and cell-to-cell spread.","authors":"Kellen Roddy, Peter Grzesik, Barbara J Smith, Nathan Ko, Sanjay Vashee, Prashant J Desai","doi":"10.1099/jgv.0.002083","DOIUrl":"10.1099/jgv.0.002083","url":null,"abstract":"<p><p>Previously, we had developed synthetic genomics methods to assemble an infectious clone of herpes simplex virus type-1 (HSV-1) strain KOS. To do this, the genome was assembled from 11 separate cloned fragments in yeast using transformation-associated recombination. Using this method, we generated null mutations in five tegument protein-coding genes as well as different combinations of these mutants. The single-locus mutants were all able to plaque on Vero cells. However, one multi-locus combination, ∆UL16/UL21, proved lethal for virus replication in non-permissive cells. The proteins encoded by the genes UL16 and UL21 are of interest because they are known to physically interact and are constituents of the tegument structure. Furthermore, their roles in HSV-1-infected cells are unclear. Both are dispensable for HSV-1 replication; however, in HSV-2, their mutation results in nuclear retention of assembled capsids and has activities that impact nuclear membrane integrity as well as activities of proteins that function in nuclear egress. We thus characterized these HSV-1 viruses that carry the single and double mutants. What we found was that the single mutants could replicate within cells and spread from infected to uninfected cells, albeit at significantly reduced levels. However, the double mutant (∆16/21) could not produce infectious progeny in a 24 h growth cycle and could not spread from cell to cell. Confocal microscopy of VP16-Venus expressed by these viruses as well as immunofluorescence assays for glycoprotein B showed perturbation of the nuclear membrane, which was pronounced in ∆21 and ∆16/21 infected cells. All the mutants assembled DNA-filled capsids as judged by ultrastructural analyses and sedimentation studies. Electron microscopy revealed the presence of numerous mature viruses in WT-infected cells but fewer such particles in the ∆16- and ∆21-infected cells. What we discovered is that in cells where both pUL16 and pUL21 are absent, cytoplasmic capsids were evident, but mature enveloped particles were not detected. The capsid particles isolated from all the single- and multi-locus mutant-infected cells showed significantly lower levels of incorporation of both VP16 and pUL37 when compared to the WT capsids. This reduced incorporation may be related to the loss of the integrity of the architecture of the nuclear membrane. Interestingly, the incorporation of pUL16 was not affected by the absence of pUL21 and vice versa, as judged by immunoblots. These data now show that of the tegument proteins, like the essential pUL36, pUL37 and VP16, the complex of pUL16 and pUL21 should be considered as important mediators of maturation and cell-to-cell spread of the particle.</p>","PeriodicalId":15880,"journal":{"name":"Journal of General Virology","volume":"106 3","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11912938/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143624895","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cytoplasmic retention of dengue virus capsid protein by metformin impairing nuclear transport.","authors":"Ian Carlos Puello-Nakayama, Jonathan Hernandez-Castillo, Juan Manuel Castillo, Daniel Talamás-Lara, Selvin Noé Palacios-Rápalo, Rosa María Del Ángel","doi":"10.1099/jgv.0.002089","DOIUrl":"10.1099/jgv.0.002089","url":null,"abstract":"<p><p>Nuclear transport of proteins larger than 60 kDa occurs via energy-dependent active transport, whereas smaller proteins diffuse into the nucleus through nuclear pore complexes via passive nuclear transport. Although the dengue virus (DENV) replication cycle primarily takes place in the cytoplasm, the capsid protein and non-structural protein 5 (NS5) are imported into the nucleus through a nuclear localization sequence-dependent mechanism. However, given its small molecular weight (14 kDa), the DENV capsid protein may also enter the nucleus via passive diffusion. While some drugs primarily inhibit active nuclear transport, few are known to block passive diffusion. Notably, biguanides have been associated with inhibitory effects on passive nuclear transport. Since biguanides such as metformin (MET) exhibit anti-DENV properties, we investigated the effects of MET on the nuclear transport of DENV proteins. Our results suggest that MET induces changes in the nuclear membrane of Huh-7 cells and reduces capsid nuclear localization without affecting NS5 nuclear import. Furthermore, MET treatment did not alter capsid nuclear import in BHK-21 cells. Additionally, mimicking MET's effects using a non-hydrolyzable ATP analogue increased capsid cytoplasmic retention and decreased DENV-2 replication. Finally, the inhibition of the classical active nuclear transport pathway did not block capsid nuclear transport, suggesting that DENV-2 capsid enters the nucleus in Huh-7 and Vero cells independently of this pathway.</p>","PeriodicalId":15880,"journal":{"name":"Journal of General Virology","volume":"106 3","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11926096/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143663558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NEDD4-binding protein 1 suppresses hepatitis B virus replication by regulating viral RNAs.","authors":"Nobuhiro Kobayashi, Saori Suzuki, Yuki Sakamoto, Rigel Suzuki, Kento Mori, Yume Kosugi, Tomoya Saito, Yuan Ma, Lihan Liang, Takuma Izumi, Kisho Noda, Daisuke Okuzaki, Yumi Kanegae, Sanae Hayashi, Yasuhito Tanaka, Atsuya Yamashita, Kohji Moriishi, Yoshiharu Matsuura, Osamu Takeuchi, Tomokazu Tamura, Akinobu Taketomi, Takasuke Fukuhara","doi":"10.1099/jgv.0.002082","DOIUrl":"10.1099/jgv.0.002082","url":null,"abstract":"<p><p>Chronic infection with hepatitis B virus (HBV) (chronic HBV infection) places patients at increased risk for liver cirrhosis and hepatocellular carcinoma. Although nucleos(t)ide analogues are mainly used for the treatment of HBV, they require long-term administration and may lead to the emergence of drug-resistant mutants. Therefore, to identify targets for the development of novel anti-HBV drugs, we screened for HBV-suppressive host factors using a plasmid expression library of RNA-binding proteins (RBPs). We tested the effect of 132 RBPs on HBV replication by ectopically expressing these proteins along with HBV in hepatocellular carcinoma and evaluated the intracellular capsid-associated HBV DNA level. Our screen identified NEDD4-binding protein 1 (N4BP1) as having an anti-HBV effect. In hepatocellular carcinoma cell lines transfected or infected with HBV, the overexpression of N4BP1 decreased core-associated HBV DNA levels, while knockdown or knockout of the gene encoding N4BP1 rescued core-associated HBV DNA levels. N4BP1 possesses the KH-like and RNase domains, and both were required for the anti-HBV effect of N4BP1. Additionally, we measured levels of HBV pregenomic RNA (pgRNA) and covalently closed circular DNA in the RBP-transfected cells and confirmed that N4BP1 binds pgRNA directly and regulates both the 3.5 and 2.4/2.1 kb HBV RNA. In summary, N4BP1 is a newly identified host factor able to counteract HBV production by regulating 3.5 and 2.1/2.4 kb HBV RNA.</p>","PeriodicalId":15880,"journal":{"name":"Journal of General Virology","volume":"106 3","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12282332/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143663559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"No evidence of subclinical infection in sheep surviving oral challenge with prions.","authors":"M Khalid F Salamat, Nora Hunter, E Fiona Houston","doi":"10.1099/jgv.0.002087","DOIUrl":"10.1099/jgv.0.002087","url":null,"abstract":"<p><p>Variant Creutzfeldt-Jakob disease (vCJD) is a fatal zoonotic disease caused by the ingestion of bovine spongiform encephalopathy (BSE)-infected meat products. Although the number of vCJD cases due to dietary exposure has significantly declined, the true burden of subclinical infections remains uncertain. Several large-scale surveys using appendix tissue samples have indicated the presence of abnormal prion protein (PrP^Sc; Sc for scrapie) in lymphoid tissue of a small proportion of the UK population. These may represent silent carriers of infection, with the potential to contribute to transmission, persistence and re-emergence of vCJD. Previously, we showed that subclinical infection is a frequent outcome of low-dose prion exposure by blood transfusion in sheep. To determine whether subclinical infection was also found following low-dose exposure by another clinically relevant route for humans, we screened archived tissues from sheep orally challenged with a range of doses of BSE, which did not show clinical or pathological signs of disease after several years of follow-up post-infection. Using a highly sensitive protein misfolding cyclic amplification assay, we were unable to detect PrP^Sc in the lymph node/tonsil of 15 sheep, or in a wider range of lymphoid tissues and brain (medulla oblongata) from a subset of 5 sheep. Our findings suggest that the route of infection/exposure may significantly influence the probability of establishing subclinical infection, with the oral route apparently much less efficient than intravenous infection by blood transfusion in sheep.</p>","PeriodicalId":15880,"journal":{"name":"Journal of General Virology","volume":"106 3","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11928478/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143674064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dynamic regulation of autophagy during Semliki Forest virus infection of neuroblastoma cells.","authors":"Robert J Stott-Marshall, Craig McBeth, Thomas Wileman","doi":"10.1099/jgv.0.002086","DOIUrl":"10.1099/jgv.0.002086","url":null,"abstract":"<p><p>Autophagy can defend against infection by delivering viruses to lysosomes for degradation. Semliki Forest virus (SFV) is a positive-sense, single-stranded RNA virus of the alphavirus genus which has been used extensively as a model for arbovirus infection and neuronal encephalitis. Here, we show that autophagy is suppressed during the early hours of SFV infection of neurons. We also show that a switch between autophagy suppression and upregulation between the early and later stages was mediated through modulation of the mammalian target of rapamycin (mTOR) activity during infection. At later stages of infection, autophagosomes colocalize with SFV nonstructural proteins suggesting the formation of a platform for virus replication. Inhibition of mTOR by torin reduced infectious virus production and intracellular virus gene expression while improving cell survival during infection. The results suggest that autophagy is suppressed early during infection of neurons to increase cell survival and then upregulated at later times to facilitate replication. This biphasic regulation of autophagy seen for SFV may be important for other arboviruses, and knowledge about the regulation of autophagy by alphaviruses may be useful for the development of antiviral therapies.</p>","PeriodicalId":15880,"journal":{"name":"Journal of General Virology","volume":"106 3","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11882037/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143557043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}