Journal of Virology最新文献

{"title":"Epidemiological, virological, and pathogenic insights into Nairobi sheep disease virus infection in sheep and goats in China.","authors":"Xin-Yan Yao, Meng-Hang Wang, Xue-Lian Zhang, Xu Zhang, De-Xin Liang, Shao-Han Li, Chun-Yang Lian, Zhi-Hang Lv, Chang-You Xia, Ming-Fa Yang, Jian-Wei Shao, Xin Yin","doi":"10.1128/jvi.00006-25","DOIUrl":"10.1128/jvi.00006-25","url":null,"abstract":"<p><p>Nairobi sheep disease virus (NSDV), a tick-borne pathogen in the <i>Orthonairovirus</i> genus of the <i>Nairoviridae</i> family, causes Nairobi sheep disease (NSD), which has mortality rates over 90% in sheep and goats. Historically, NSD outbreaks in East Africa and South Asia have led to considerable economic losses. Although NSDV genomic fragments have been detected in ticks in China, there has been a notable absence of reported infections in local sheep and goats. In this study, we report the first identification of NSDV infection in sheep and goats in China. Through meta-transcriptomics sequencing, NSDV was found in infected spleen tissue with high viral abundance. Epidemiological investigations indicated a 4.1% positive rate for NSDV RNA and a 29.9% seroprevalence rate, confirming the presence of NSDV infection in these herds. Sequence analyses showed that the identified NSDV clustered with those previously found in ticks in China but were distinct from Africa or India strains. Furthermore, these viruses could be categorized into different sub-clades, suggesting the genetic diversity of NSDV in China. Remarkably, NSDV was isolated from infected sheep for the first time in China, and the isolated virus could cause severe clinical signs, leading to sheep mortality. In summary, this study represents the initial identification of NSDV in vertebrate hosts in China and highlights the importance of NSDV surveillance to prevent outbreaks of NSD within the country.IMPORTANCEAs a significant tick-borne virus, Nairobi sheep disease virus (NSDV) has caused devastating disease known as Nairobi sheep disease (NSD) in small ruminants in East Africa and South Asia. Although NSDV genomic fragments have been detected in ticks within China, there has been little information on its infection in local sheep or goats. This study confirms, for the first time, the infection of NSDV among these animals in China. Additionally, the successful isolation of NSDV from infected sheep highlights its capacity to replicate in various cell lines, including those of human origin, thereby underscoring its broad host range and potential for cross-species transmission. Notably, animal experiments demonstrated that the isolated virus strain could cause severe clinical signs in sheep. These findings provide the first evidence for the presence of NSDV infection among sheep and goats in China, underscoring the critical need for NSDV surveillance to prevent outbreaks of NSD within the country.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0000625"},"PeriodicalIF":4.0,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12172417/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144111134","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A single amino acid mutation in VP1 of coxsackievirus A6 determining efficiency of VP0 cleavage and proliferation.","authors":"Yihao Sun, ShaSha Qian, Yaxin Du, Jiahui Wu, Hadireya Rehemutula, Shengli Meng, Zejun Wang, Jing Guo, Shuo Shen","doi":"10.1128/jvi.00128-25","DOIUrl":"10.1128/jvi.00128-25","url":null,"abstract":"<p><p>Coxsackievirus A6 (CV-A6) has emerged as a major pathogen associated with hand, foot, and mouth disease (HFMD), capable of infecting both children and adults. However, currently, there is no effective vaccine to prevent HFMD caused by non-EV-A71 enteroviruses. In this study, a pair of CV-A6 strains was selected from a rhabdomyosarcoma (RD)-isolated and Vero-adapted stock with a difference of 7 nucleotides in their genomes, resulting in three amino acid mutations in the structural proteins. Distinct differences in propagation, virulence in cells, and plaque size were observed. A series of single-site mutants was constructed, and a single mutation in VP1-143 was mapped to associate with phenotype changes. The mutation from glycine to arginine at VP1-143 dramatically increased infectivity but decreased virulence, growth rate, and plaque size. Furthermore, the experiments using both purified whole virus and full particle (FP) demonstrated that glycine-to-arginine mutation increased VP0 cleavage efficiency because of decreased VP0/VP2 ratio. The decrease in VP0 cleavage efficiency led to the accumulation of non-infectious provirion. The efficiency of virus transmission between cells determined the rates of viral RNA (vRNA) and protein synthesis and was related to fast-slow growth and virulence phenotypes. In addition, the data indicated that the mutation did not affect the encapsidation of the genomic RNA, and the ratio of empty and full particles was unchanged. The results are important for understanding the mechanism of VP0 cleavage regulation and are relevant to developing vaccines and therapeutic reagents against CV-A6 infection and diseases.</p><p><strong>Importance: </strong>CV-A6 is a major pathogen in the context of HFMD. The cost of treatment and hospitalization of children with HFMD may have a considerable financial impact on the families of patients. CV-A6 is a member of picornaviruses and forms infectious virion through maturation cleavage of VP0 into VP4 and VP2. Although it is well accepted that the autocatalytic process involves viral RNA, the detailed mechanism remains unclear. In this study, residues in VP1-143 were demonstrated to regulate the efficiency of VP0 cleavage and affect the ratio of provirion and virion. Glycine-to-arginine mutation was tolerant, not abolished, but affected the efficiency of VP0 cleavage. The results support a theory that residue mutations on a structural protein of a serotype/genotype within enteroviruses, not well-conserved across picornaviruses and far away from the VP0 cleavage site on the outside surface, regulate the efficiency of VP0 cleavage and render phenotypically different strains.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0012825"},"PeriodicalIF":4.0,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12180516/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144000736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ineffectual immunity in a resurrected mouse model of persistent viremia.","authors":"Kylie Nennig, Teressa Shaw, Logan Borsinger, Adam L Bailey","doi":"10.1128/jvi.00248-25","DOIUrl":"10.1128/jvi.00248-25","url":null,"abstract":"<p><p>Viruses that establish persistent (i.e., chronic) infections have evolved sophisticated strategies to avoid clearance by the host immune system. This is particularly true for viruses that infect immunocompetent mammals and sustain high infectious burdens in body sites under intense immune surveillance (i.e., the blood, a.k.a., \"viremia\"). Historically, lymphocytic choriomeningitis virus (LCMV) infection of laboratory mice has served as a powerful model to understand mechanisms of failed immunity, but other viruses may have unique and underappreciated persistence strategies. Here, we resurrect a bygone model of viral persistence-lactate dehydrogenase-elevating virus (LDV)-and use modern transgenic mouse technologies to investigate various aspects of anti-viral immunity. We find that interferons have a modest impact on LDV replication, with interferon-alpha blunting LDV viremia in the acute phase of the infection and interferon-gamma reducing LDV viral loads in the chronic phase of infection, but only when paired with an intact interferon-alpha response. Adaptive immunity, assessed in Rag-knockout mice, had only a modest impact on LDV viremia, and only during the sub-acute phase of infection. Mice lacking the critical immune checkpoint molecule PD-1 showed no signs of disease and supported LDV viral loads at levels equivalent to their wild-type counterparts. Altogether, these results point to a novel and highly effective mechanism of persistence that is minimally impacted by conventional aspects of anti-viral immunity or immune exhaustion-a rarity among persistent viruses. Given the relative paucity of chronic infection models in the laboratory mouse, LDV infection may be useful for exploring unique modes of immune system failure.</p><p><strong>Importance: </strong>Viruses that infect a host over long periods of time have evolved unique strategies to evade the host immune system. Of particular interest are viruses that cause persistent infection in the laboratory mouse-the most well-developed tool for studying the mammalian immune system. Here, we resurrected a model of persistent RNA virus infection (lactate dehydrogenase-elevating virus, LDV) and applied modern tools of mouse immunology to further characterize its persistence. We found that host factors that typically have a dramatic effect on viral infections-e.g., the interferon system and lymphocytes-had very little impact on LDV infection. Removing \"checks\" on immune activation also had little effect on the virus or host health. Altogether, these findings imply that LDV uses a unique and highly effective mechanism to avoid immune clearance. Understanding this mechanism has implications for understanding ways in which the immune system fails.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0024825"},"PeriodicalIF":4.0,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12172470/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144002743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unraveling the cross-talk between a highly virulent PEDV strain and the host via single-cell transcriptomic analysis.","authors":"Yanan Wang, Yu Cheng, Shuai Wang, Dan Liu, Yueyi Gao, Jiaxuan Li, Yanping Jiang, Wen Cui, Xinyuan Qiao, Yijing Li, Li Wang","doi":"10.1128/jvi.00555-25","DOIUrl":"10.1128/jvi.00555-25","url":null,"abstract":"<p><p>Porcine epidemic diarrhea virus (PEDV) causes severe intestinal damage and high mortality in neonatal piglets. The continuous emergence of new strains has brought new challenges to prevention and control. In this study, we isolated and characterized a prevalent PEDV virulent strain and analyzed 19,612 jejunal cells from PEDV-infected and control piglets using single-cell sequencing, revealing significant changes in cellular composition, gene expression, and intercellular communication. In response to PEDV infection, epithelial repair was enhanced through increased proliferation and differentiation of stem cells, transit-amplifying (TA) cells, and intestinal progenitor cells into enterocytes. Additionally, PEDV disrupted intercellular communication, compromising epithelial functionality while triggering immune responses, with IFN-γ and IL-10 signaling activation acting as critical regulators of immune balance and tissue homeostasis. Beyond enterocytes, viral genes were detected in various other cell types. Further experiments confirmed that PEDV could initiate replication in B and T lymphocytes but was unable to produce infectious progeny, with T cells additionally undergoing virus-induced apoptosis. These findings provide new insights into PEDV tropism, immune evasion, and epithelial repair, revealing complex host-pathogen interactions that shape disease progression and tissue regeneration, thereby contributing to a better understanding of enteric coronavirus pathogenesis.IMPORTANCEThe persistent circulation of porcine epidemic diarrhea virus (PEDV) poses a major threat to the swine industry, with emerging strains complicating prevention and control efforts. Currently, no effective measures completely prevent virus transmission, highlighting the need to understand PEDV-host interactions. In this study, we isolated a prevalent virulent strain and used single-cell sequencing to identify new PEDV-infected cell types and explore the complex interplay between the host and PEDV. These findings provide essential insights into viral pathogenesis and facilitate the design of targeted antiviral interventions.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0055525"},"PeriodicalIF":4.0,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12172440/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144111136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative study on the virulence of mycobacteriophages.","authors":"Ilaria Rubino, Carlos A Guerrero-Bustamante, Melissa Harrison, Sheila Co, Isobel Tetreau, Mani Ordoubadi, Sasha E Larsen, Rhea N Coler, Reinhard Vehring, Graham F Hatfull, Dominic Sauvageau","doi":"10.1128/jvi.01920-24","DOIUrl":"10.1128/jvi.01920-24","url":null,"abstract":"<p><p>The global tuberculosis (TB) epidemic affected 10 million people and caused 1.3 million deaths in 2022 alone. Multidrug-resistant TB is successfully treated in less than 60% of cases by long, expensive, and aggressive treatments. Mycobacteriophages, viruses that can infect bacteria such as <i>Mycobacterium tuberculosis</i>-the species responsible for TB-have the potential to redefine TB prevention and treatments. However, the development of phage-based products necessitates the assessment of numerous parameters, including virulence and adsorption, to ensure their performance and quality. In this work, we characterized the virulence of three different mycobacteriophages (Fionnbharth, Muddy, and D29), alone and as cocktails, against a TB model host (<i>Mycobacterium smegmatis</i>) under planktonic and early-stage biofilm growth conditions. Phage D29 and cocktails containing D29 had the highest virulence under all conditions. Interestingly, phages Fionnbharth and Muddy and their combination showed higher virulence against early-stage biofilm than against the planktonic phenotype. Adsorption assays indicated that all three phages had lower adsorption efficiencies on the early-stage biofilm phenotype than on the planktonic one, suggesting a reduced availability of receptors in the former. Given that, despite these lower adsorption efficiencies, the virulence of the phages and phage cocktails was either unchanged or higher against the early-stage biofilm, this phenotype must display properties that are favorable to other steps of the infection process. These results inform us on the dynamics of mycobacteriophage infections, both alone and in cocktail formulations, under different host growth conditions, serving as a basis for the development of phage products targeting mycobacteria biofilms.</p><p><strong>Importance: </strong>This study provides a systematic investigation of the virulence of three mycobacteriophages, Fionnbharth, Muddy, and D29, and their combinations as cocktails against <i>Mycobacterium smegmatis</i>. We also included considerations on the hydrodynamic conditions (shaking and not shaking) and host phenotype (planktonic and early-onset biofilm cultures) during the infection process and adsorption of the phage to the host. We showed that virulence was strongly affected by phenotype and that higher virulence shown against the early-onset biofilm phenotype was not linked to faster adsorption to the host. We also showed that phage D29 and cocktails containing this phage had the highest virulence. These results are important as they provide a framework for a better evaluation and development of phage-based treatment against mycobacterial infections.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0192024"},"PeriodicalIF":4.0,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12172466/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144111130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Basic patches on the E2 glycoprotein of eastern equine encephalitis virus influence viral vascular clearance and dissemination in mice.","authors":"Stephanie E Ander, Erin R Fish, Mariana O L da Silva, Bennett J Davenport, M Guston Parks, Thomas E Morrison","doi":"10.1128/jvi.00602-25","DOIUrl":"10.1128/jvi.00602-25","url":null,"abstract":"<p><p>Previously, we found that chimeric Sindbis-eastern equine encephalitis virus (SINV-EEEV) particles can be removed from the murine blood circulation in a phagocyte-dependent manner which can be disrupted by either transient depletion of vascular heparan sulfate (HS) glycosaminoglycans (GAGs), or mutation of the viral E2 glycoprotein (K71/74/77A) associated with decreased GAG binding <i>in vitro</i>. Here, we further investigate the viral determinants of EEEV vascular clearance and evaluate their role in viremia development. We identified two large basic patches on the EEEV E2 glycoprotein which contain two known GAG-binding sites (K71/74/77 and K156/R157) and six additional basic residues (K10, R13, K56, R152, K231, and K232). We find that disruption of either basic patch by single alanine substitutions promotes prolonged retention of SINV-EEEV particles in the murine blood circulation in an experimental viremia model. Furthermore, we observed that the K156/R157A, K10A, and K231A mutations are also associated with similar viral dissemination in a mouse infection model as the attenuated K71/74/77A mutant. Surprisingly, despite known differences in GAG binding and potential alteration in receptor interactions, we find the initial dispersal of wild-type (WT) and mutant SINV-EEEV virions from the inoculation site to the draining lymph node to be equivalent at 1 hour post-subcutaneous inoculation. Moreover, our data suggest the higher viremia associated with mutation of the E2 basic patches may be attributed to evasion of viremic control by blood-filtering phagocytes. Overall, this study defines viral features of the EEEV E2 glycoprotein that influence tissue-specific viral dissemination and highlights the capacity of blood-filtering phagocytes to modulate EEEV viremia.IMPORTANCEVirus-GAG interactions have long been studied <i>in vitro</i>; however, investigating the impact of these interactions <i>in vivo</i> has been challenging. Previously, we showed that blood-filtering phagocytes and vascular HS mediate the removal of enhanced GAG-binding WT SINV-EEEV virions from the blood circulation in a reductionist, experimental viremia model. Here, we demonstrate that single-residue, charge-neutralizing mutations within basic patches of the E2 glycoprotein are sufficient both to promote viral evasion of vascular clearance and viral dissemination in an infection model. We also find that the WT and decreased GAG-binding SINV-EEEV virions traffic similarly from a subcutaneous inoculation until drainage into the bloodstream, upon which the WT virus is selectively depleted. These observations suggest viral dissemination is influenced by tissue-specific, virion-GAG interactions.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0060225"},"PeriodicalIF":4.0,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12172491/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144094159","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ANP32 proteins from ticks and vertebrates are key host factors for replication of Bourbon virus across species.","authors":"Zhenyu Zhang, Ishmael D Aziati, Thomas Nipper, Adrianus C M Boon, Andrew Mehle","doi":"10.1128/jvi.00522-25","DOIUrl":"10.1128/jvi.00522-25","url":null,"abstract":"<p><p>Bourbon virus (BRBV) is a tick-borne virus in the genus <i>Thogotovirus</i> in the <i>Orthomyxoviridae</i> family. BRBV was initially identified as the presumptive causative agent of a fatal human infection in 2014 and has since been identified in ticks in the Midwest, Northeast, and Southern United States, with occasional spillovers into humans. However, little is known about how virus-host interactions impact their large host range. Here, we show that BRBV polymerase activity in human cells is completely dependent on cellular ANP32 proteins. BRBV polymerase activity was completely lost in cells lacking ANP32A and ANP32B, resulting in failed infections. BRBV polymerase activity was restored in the presence of ANP32 proteins from diverse hosts. Dhori virus and Thogoto virus, other related <i>Thogotovirus</i> members, retained high activity in the absence of ANP32 proteins, showing reduced dependence on these host factors. Interaction studies revealed that the BRBV polymerase trimer binds human ANP32A or ANP32B. Genetic analysis revealed that tick vectors for BRBV encode a single <i>ANP32</i> locus corresponding to <i>ANP32A</i>. Tick <i>ANP32A</i> produces multiple protein variants through alternative splicing and start-site selection, all of which enhance polymerase activity for <i>Thogotoviruses</i>. Unexpectedly, the BRBV polymerase was highly sensitive to changes at the N-terminus of ANP32, while it was insensitive to changes in the body of ANP32 that restrict the activity of influenza virus polymerases. Thus, ANP32A is a deeply conserved pro-viral cofactor, and <i>Thogotoviruses</i> show remarkable plasticity utilizing ANP32 homologs from different hosts separated by almost 1 billion years of evolution.IMPORTANCEViral polymerases rely on cellular cofactors to support efficient transcription of viral genes and replication of the viral genome. The RNA-dependent RNA polymerase of influenza virus, an orthomyxovirus, requires the cellular ANP32A or ANP32B proteins for genome replication. However, little is known about whether ANP32 proteins are required by other orthomyxovirus family members, like the tick-borne thogotoviruses. We show that thogotoviruses use ANP32 proteins from diverse hosts to enhance polymerase activity, including that encoded by the single <i>ANP32A</i> gene found in ticks. However, thogotovirus polymerase showed varying levels of dependence on ANP32 proteins, with some polymerases functioning at near full activity even in the absence of ANP32 proteins. Thus, ANP32 proteins are deeply conserved viral cofactors, with each virus displaying distinct patterns of ANP32 usage and requirements for function.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0052225"},"PeriodicalIF":4.0,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12172476/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143971195","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IFNβ absence compensates for LAT functions in latency reactivation and T cell exhaustion.","authors":"Shaohui Wang, Ujjaldeep Jaggi, Jay J Oh, Homayon Ghiasi","doi":"10.1128/jvi.00374-25","DOIUrl":"10.1128/jvi.00374-25","url":null,"abstract":"<p><p>Type I interferons (IFNs) generate strong antiviral immunity following viral infection in mice and humans. These type I IFNs are encoded by at least 14 IFNα genes and a single IFNβ gene. We showed that the absence of one of the IFNα genes (IFNα2A^-/-) affected latency levels in herpes simplex virus type 1 (HSV-1) ocularly infected mice but not in infected control mice, and the absence of IFNα2A did not affect viral reactivation in ocularly infected mice. Since the role of IFNβ in HSV-1 latency reactivation and the potential effect of latency-associated transcript (LAT) on IFNβ activity is not known, we ocularly infected IFNβ^-/- mice with different doses of LAT-plus [LAT(+)] and LAT-minus [LAT(-)] viruses. Wild-type (WT) control mice and IFNβ^-/- mice were infected similarly. Virus titers in the eye, viral and cellular transcripts in the eye and trigeminal ganglia (TG) of infected mice on days 3 and 5 post-infection, eye disease, survival, latency-reactivation levels, and T cell exhaustion were measured in latently infected mice. Virus replication and viral and cellular transcripts in the eye of infected IFNβ^-/- mice were similar to those in WT mice, while eye disease and survival in IFNβ^-/- mice differed significantly from WT mice. WT mice infected with LAT(-) virus showed reduced latency, slower reactivation, and less T cell exhaustion than mice infected with LAT(+) virus. However, using different doses of each virus, latency levels, time of reactivation, and T cell exhaustion were similar between LAT(+) and LAT(-) viruses. These results suggest that the absence of IFNβ expression compensates for the function of LAT with regard to levels of latency, T cell exhaustion, and reactivation but does not affect viral and cellular transcripts during primary infection.IMPORTANCEInterferon β (IFNβ) is a type I interferon that plays an important role in controlling primary herpes simplex virus type 1 (HSV-1) infection. To evaluate the importance of IFNβ on HSV-1 latency reactivation and its relationship to LAT, we infected IFNβ^-/- mice with LAT(+) and LAT(-) viruses. In the absence of IFNβ, latency levels in mice infected with LAT(-) virus were similar to those of mice infected with LAT(+) virus. The absence of IFNβ also reduced the time of reactivation in mice infected with LAT(-) virus to that of LAT(+) virus. Our results show a strong correlation between the functions of LAT and IFNβ during latent but not primary stages of HSV-1 infection.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0037425"},"PeriodicalIF":4.0,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12172465/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144016958","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rubella virus mutations that confer resistance to inactivation at low pH.","authors":"Pratyush Kumar Das, Margaret Kielian","doi":"10.1128/jvi.00255-25","DOIUrl":"10.1128/jvi.00255-25","url":null,"abstract":"","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0025525"},"PeriodicalIF":4.0,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12172415/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144078650","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Apolipoprotein E selectively supports gammaherpesvirus replication in macrophages.","authors":"Damon L Schmalzriedt, Carlie A Aurubin, Cade R Rahlf, Matthew A Brown, Jordan M Bobek, Philip T Lange, Xander G Bradeen, Daisy Sahoo, Vera L Tarakanova","doi":"10.1128/jvi.00480-25","DOIUrl":"10.1128/jvi.00480-25","url":null,"abstract":"<p><p>Gammaherpesviruses establish lifelong infections in over 90% of adults worldwide and contribute to the development of several cancers. Endogenous lipid synthesis pathways support lytic and latent life cycles of several gammaherpesviruses. However, the role of circulating lipoproteins and the corresponding apolipoproteins in gammaherpesvirus infection remains unknown. Apolipoprotein E (ApoE) is a protein that associates with lipoproteins in circulation and supports bidirectional lipid transport to maintain lipid homeostasis. Interestingly, ApoE differentially affects several virus families, but its role in gammaherpesvirus infection has not been evaluated. In this study, we demonstrate that ApoE expression was increased in murine gammaherpesvirus 68 (MHV68)-infected macrophages in a type-I interferon (IFN)-dependent manner. Intriguingly, ApoE expression was usurped to support MHV68 lytic replication and expression of lytic viral genes. The proviral effects of ApoE in macrophages were independent of the conventional functions of ApoE in the regulation of endogenous lipid synthesis and type I IFN signaling. Finally, the proviral effects of ApoE were limited to the lytic life cycle, as the establishment of MHV68 latency in macrophages was not altered by the ApoE genotype of chronically infected mice. Thus, our study defines a viral life cycle-specific proviral role of ApoE in gammaherpesvirus infection.</p><p><strong>Importance: </strong>ApoE is an apolipoprotein that mediates lipid transport and exchange between tissues and the circulation. ApoE differentially affects several virus families, but its role in gammaherpesvirus infection remains unknown. Here, we show that ApoE supported lytic gammaherpesvirus replication in primary macrophages and that infected macrophages increased expression of ApoE in an interferon-dependent manner. However, ApoE expression did not affect viral latency <i>in vivo</i>, implying a novel viral life cycle-specific proviral role for ApoE in gammaherpesvirus infection.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0048025"},"PeriodicalIF":4.0,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12172433/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144173910","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}