Journal of Virology最新文献

{"title":"Diversity and transmissibility of RNA viruses in the small brown planthopper, <i>Laodelphax striatellus</i>.","authors":"Qianzhuo Mao, Zhuang-Xin Ye, Jing-Na Yuan, Chao Ning, Meng-Nan Chen, Zhong-Tian Xu, Yu-Hua Qi, Yan Zhang, Ting Li, Yu-Juan He, Gang Lu, Hai-Jian Huang, Jia-Bao Lu, Ji-Chong Zhuo, Qing-Ling Hu, Chuan-Xi Zhang, Jian-Ping Chen, Jun-Min Li","doi":"10.1128/jvi.00191-24","DOIUrl":"10.1128/jvi.00191-24","url":null,"abstract":"<p><p>While a considerable number of viruses have been recently discovered in hematophagous insects, there remains insufficient research on virus diversity and their association with phytophagous insect hosts. In this study, we conducted a systematic investigation of the RNA virome in the small brown planthopper (SBPH), <i>Laodelphax striatellus</i>, an important vector of plant viruses. We successfully identified a total of 22 RNA viruses, including 17 novel viruses, from various families. These viruses were prevalent and abundant in SBPH populations, originating from the lab or field, with +ssRNA viruses composing the core SBPH viruses. Subsequent analysis revealed that the overall abundance of RNA viruses in SBPH remained relatively consistent across different developmental stages of the insects, although the titers of individual viruses varied among different insect tissues. This indicates a delicate balance between the viruses and their insect hosts. Interestingly, cross-species experiments confidently indicated that certain SBPH viruses could successfully infect and replicate in two other rice planthopper species (the brown planthopper and the white-backed planthopper) through microinjection. In conclusion, this study provides valuable insights into the RNA virome and its adaptability in a phytophagous insect, contributing to a better understanding of the intimate relationship between viruses and host insects.</p><p><strong>Importance: </strong>In the last decade, advances in the next-generation sequencing technology have unveiled a vast diversity of viruses in insects, particularly RNA viruses in hematophagous insects. However, research on virus diversity and their association with phytophagous insect hosts remains insufficient. This study presents a comprehensive analysis of the RNA virome in the small brown planthopper (SBPH), <i>Laodelphax striatellus</i>, a critical vector of plant viruses. The results indicated that the +ssRNA viruses, especially picorna-like viruses, comprised the core RNA viruses of SBPH that were prevalent in both laboratory and field populations. Moreover, a delicate balance was observed between the viruses and insect hosts. Significantly, some RNA viruses of SBPH could successfully infect and replicate in two other rice planthopper species belonging to different genera. This study provides valuable insights into the RNA virome and its adaptability in a phytophagous insect.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0019124"},"PeriodicalIF":4.0,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11650995/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142716473","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":"Lipid nanoparticles as adjuvant of norovirus VLP vaccine augment cellular and humoral immune responses in a TLR9- and type I IFN-dependent pathway.","authors":"Weiqian Dai, Man Xing, Lingjin Sun, Lihui Lv, Xiang Wang, Yihan Wang, Xueyang Pang, Yingying Guo, Jiling Ren, Dongming Zhou","doi":"10.1128/jvi.01699-24","DOIUrl":"10.1128/jvi.01699-24","url":null,"abstract":"<p><p>Norovirus (NoV) virus-like particles (VLPs) adjuvanted with aluminum hydroxide (Alum) are common vaccine candidates in clinical studies. Alum adjuvants usually inefficiently assist recombinant proteins to induce cellular immune responses. Thus, novel adjuvants are required to develop NoV vaccines that could induce both efficient humoral and robust cellular immune responses. Lipid nanoparticles (LNPs) are well-known mRNA delivery vehicles. Increasing evidence suggests that LNPs may have intrinsic adjuvant activity and can be used as adjuvants for recombinant protein vaccines; however, the underlying mechanism remains poorly understood. In this study, we compared the adjuvant effect of LNPs and Alum for a bivalent GI.1/GII.4 NoV VLP vaccine. Compared with Alum, LNP-adjuvanted vaccines induced earlier production of binding, blocking, and neutralizing antibodies and promoted a more balanced IgG2a/IgG1 ratio. It is crucial that LNP-adjuvanted vaccines induced stronger Th1-type cytokine-producing CD4⁺ T cell and CD8⁺ T cell responses than Alum. The adjuvant activity of LNPs depended on the ionizable lipid components. Mechanistically, LNPs activated innate immune responses in a type I IFN-dependent manner and were partially dependent on Toll-like receptor (TLR) 9, thus affecting the adaptive immune responses of the vaccine. This conclusion was supported by RNA-seq analysis and <i>in vitro</i> cell experiments and by the deeply blunted T cell responses in IFNαR1^-/- mice immunized with LNP-adjuvanted vaccines. This study not only identified LNPs as a high quality adjuvant for NoV VLP vaccines, but also clarified the underlying mechanism of LNPs as a potent immunostimulatory component for improving protein subunit vaccines.IMPORTANCEWith the rapid development of mRNA vaccines, recurrent studies show that lipid nanoparticles (LNPs) have adjuvant activity. However, the mechanism of its adjuvant effect in protein vaccines remains unknown. In this study, we found that the LNP-adjuvanted norovirus bivalent virus-like particle vaccines led to durable antibody responses as well as Th1-type cytokine-producing CD4⁺ T cell and CD8⁺ T cell responses, which exceeded the efficiency of the conventional adjuvant aluminum hydroxide. Mechanistically, LNPs activated innate immune responses in a type I IFN-dependent manner and were partially dependent on Toll-like receptor 9, thus affecting the adaptive immune responses of the vaccine. This work unveils that LNPs as a potent immunostimulatory component may be ideal for generating CD8⁺ T cell and B cell responses for recombinant protein vaccines.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0169924"},"PeriodicalIF":4.0,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11650981/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142569072","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":"Age-specific dynamics of neutralizing antibodies, cytokines, and chemokines in response to La Crosse virus infection in mice.","authors":"Reem Alatrash, Varun Vaidya, Bobby Brooke Herrera","doi":"10.1128/jvi.01762-24","DOIUrl":"10.1128/jvi.01762-24","url":null,"abstract":"<p><p>La Crosse virus (LACV) is a primary cause of pediatric arboviral encephalitis in the United States, particularly affecting children aged 16 years or younger. This age-related susceptibility extends to murine models, where weanling mice (3 weeks old) succumb to LACV infection, while adults (≥6 weeks old) demonstrate resistance. Despite its clinical relevance, the host immune response to LACV is not fully understood. In this study, we investigated the roles of neutralizing antibodies (nAbs), cytokines, and chemokines in weanling and adult mice following infection with 5 × 10⁵ plaque-forming units (PFU) of LACV. Weanling mice demonstrated early disease onset with elevated peripheral viremia, but passive transfer of adult serum, confirmed to have nAbs, to naïve weanlings prior to infection completely rescued them from death. Moreover, adult mice had increased Th1 cytokines, Th9/Th17/Th22/Treg cytokines, and many chemokines. In contrast, weanlings had higher Th2 cytokines, correlating with symptoms onset. Flow cytometry and intracellular cytokine staining further demonstrated that weanling mice produced higher levels of IL-4 by CD4⁺ and CD8⁺ T cells compared to adults, regardless of infection status. Conversely, LACV-infected adult mice had increased IFN-γ production by CD8⁺ T cells compared to uninfected controls. Finally, the adoptive transfer of splenocytes from immune adult mice to naïve weanlings delayed neurological symptoms and improved survival. In conclusion, this study links nAbs and cytokine and chemokine responses to protective immunity in adult mice, contrasting with the pathogenesis seen in weanlings. These findings underscore the importance of further research into innate and adaptive immune mechanisms during LACV infection.IMPORTANCELa Crosse virus (LACV) is a primary cause of pediatric encephalitis in the United States, with an impact on children aged 16 years or younger. This age-related susceptibility is recapitulated in mouse models, where young mice succumb to LACV-induced disease, while adults demonstrate resistance. Our understanding of host responses to LACV remains underexplored. This study sheds light on the dynamics of neutralizing antibodies (nAbs), cytokines, and chemokines following LACV infection in both adult and weanling mice. Our study reveals age-specific variations in viremia, neutralizing antibody titers, survivability, and levels of cytokines and chemokines. Adult mice exhibit significantly elevated levels of Th1 cytokines, contrasting with elevated levels of Th2 cytokines observed in weanling mice, often coinciding with the onset of symptoms. These data reveal age-specific dynamics in cytokines and chemokines associated with protective versus pathogenic immunity, emphasizing the need for further studies on innate and adaptive immunity.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0176224"},"PeriodicalIF":4.0,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11651005/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142583776","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":"Lethal model for respiratory syncytial virus infection using C57BL/6 mice.","authors":"Tatsuki Takahashi, Sodbayasgalan Amarbayasgalan, Shiori Ueno, Yoshiro Sugiura, Enkhjin Dorjsuren, Kenta Shimizu, Wataru Kamitani","doi":"10.1128/jvi.01772-24","DOIUrl":"10.1128/jvi.01772-24","url":null,"abstract":"<p><p>Respiratory syncytial virus (RSV) infection is a major infectious disease affecting public health. Infants and elderly infected with RSV can develop severe respiratory symptoms. A mouse model mimicking human RSV infection could be useful in elucidating the pathogenesis of RSV. However, previous mouse models did not adequately mimic the pathophysiology of human patients. We attempted to establish a new mouse-adapted RSV strain via serial passaging of mice. We rescued the MP11 virus (which had one non-synonymous substitution in each of the F, G, and L genes) through serial passaging in mice. The MP11 virus was inoculated into mice to evaluate whether it had adapted to the mouse. Viral RNA levels in the lungs of 25-week-old mice infected with MP11 virus were higher than those in the lungs of mice infected with A2 virus. There was a high infiltration of inflammatory cells and high expression of several inflammatory cytokines (IFN-γ, CCL2, TNF-α, and IL-6) in the MP11 virus-infected lungs. Furthermore, the MP11 virus can also cause lethal pneumonia in mice via high-concentration inoculation. These results indicated that the MP11 virus is a more mouse-adapted strain than the A2 virus. We generated a recombinant MP11 virus (rMP11) using reverse genetics. The rMP11 virus could grow in the lungs of mice, similar to the parent MP11 virus. In conclusion, we successfully established a new mouse-adapted strain, MP11, and reverse genetics for this strain. These MP11 and rMP11 viruses could contribute to mouse experiments aimed at elucidating RSV pathogenesis.</p><p><strong>Importance: </strong>A mouse model of respiratory syncytial virus (RSV) infection is useful for fundamental research aimed at developing antiviral drugs. Previous mouse models of RSV infection were unable to adequately mimic the pathophysiology of human patients due to the low amplification efficiency of this virus in the mouse lung. Furthermore, mice other than BALB/C mice are difficult to use for the RSV infectious model. We established a new mouse-adapted RSV strain, MP11. The MP11 virus can cause severe pneumonia in C57BL/6 mice and efficiently replicate and induce inflammation in the lung. Therefore, C57BL/6 mice can be used for RSV infection experiments using MP11 virus. We established a reverse genetics system for the MP11 virus using our mouse model. This system enables detailed analyses of the MP11 virus, such as functional analysis of each viral protein. Our study provides techniques that can advance fundamental research in elucidating the pathogenesis of RSV infections.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0177224"},"PeriodicalIF":4.0,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11651003/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142583784","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":"Single-cell RNA-sequencing of BK polyomavirus replication in primary human renal proximal tubular epithelial cells identifies specific transcriptome signatures and a novel mitochondrial stress pattern.","authors":"Fabian H Weissbach, Océane M Follonier, Svenia Schmid, Karoline Leuzinger, Michael Schmid, Hans H Hirsch","doi":"10.1128/jvi.01382-24","DOIUrl":"10.1128/jvi.01382-24","url":null,"abstract":"&lt;p&gt;&lt;p&gt;BK polyomavirus (BKPyV) contributes to premature renal failure in 10%-20% of kidney transplant recipients. Current treatment relies on reducing immunosuppression to regain BKPyV-specific immune control. Subsequently, declining allograft function may result from persisting viral cytopathology, BKPyV-specific immune reconstitution, or alloimmunity/rejection, all being poorly distinguishable by current histological or molecular approaches. To reduce the complexity encountered in BKPyV-replicating kidneys, we analyzed differentially expressed genes (DEGs) in primary human renal proximal tubular epithelial cells at 24 and 48 h post-infection (hpi) using single-cell RNA-sequencing (10x-Genomics-3´ kit). At 24 hpi, viral transcript reads predominantly mapped to the early viral gene region (&lt;i&gt;EVGR&lt;/i&gt;) and shifted to &gt;100-fold higher late viral gene region (&lt;i&gt;LVGR&lt;/i&gt;) levels at 48 hpi, matching the sequential bi-directional viral protein expression from the circular double-stranded BKPyV-DNA genome. Besides expected coverage \"hills\" at viral 3´-poly-A sites, unexpected \"spike\" and \"pulse\" reads resulted from off-target TSO priming. \"Spike\" and \"pulse\" patterns were rare for the mostly unidirectional reads mapping to the circular mitochondrial genome. Bioinformatic curation removed \"spikes\" and \"pulses\" and reclassified 10% of DEGs in renal proximal tubular epithelial cells (RPTECs). Up-regulated gene ontologies included S and G2/M phase, double-stranded DNA repair, proximal tubulopathy, and renal tubular dysfunction, whereas allograft rejection, antigen presentation, innate immunity, translation, and autophagy were down-regulated. BKPyV-&lt;i&gt;LVGR&lt;/i&gt; expression induced a novel mitochondrial cell stress pattern consisting of discordant up-regulation and down-regulation of mitochondria-encoded and nucleus-encoded mitochondrial genes, respectively. We explored which top-scoring gene sets of late-phase BKPyV-replicating RPTECs can identify BKPyV-associated nephropathy in kidney transplant biopsies. The results should facilitate distinguishing BKPyV-associated pathology from other entities in kidney transplant biopsies.IMPORTANCEBK polyomavirus (BKPyV) infects more than 90% of the general population and then persists in the reno-urinary tract. Subsequently, low-level urinary shedding is seen in 10% of healthy BKPyV-seropositive persons, indicating that BKPyV replication occurs despite the presence of virus-specific cellular and humoral immunity. Notably, transplantation of donor kidneys with low-level BKPyV replication is a risk factor for progression to high-level BKPyV viruria, new-onset BKPyV-DNAemia and biopsy-proven BKPyV nephropathy. Here, we identify a short list of robust up- and down-regulated nucleus-encoded differentially expressed genes potentially allowing to discriminate viral from allograft immune damage. By carefully curating viral and mitochondrial transcriptomes, we identify a novel virus-associated mitochondrial stress pattern of up-","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0138224"},"PeriodicalIF":4.0,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11657676/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142603331","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":"Protective threshold of a potent neutralizing Zika virus monoclonal antibody in rhesus macaques.","authors":"Joseph P Nkolola, David Hope, Ruoran Guan, Alessandro Colarusso, Malika Aid, Deborah Weiss, John Misamore, Hanne Andersen, Mark G Lewis, Lauren Williamson, Robert H Carnahan, James E Crowe, Dan H Barouch","doi":"10.1128/jvi.01429-24","DOIUrl":"10.1128/jvi.01429-24","url":null,"abstract":"<p><p>Zika virus (ZIKV) is a mosquito-borne flavivirus that caused a global pandemic in 2016-2017 with continued ongoing transmission at low levels in several countries. In the absence of an approved ZIKV vaccine, neutralizing monoclonal antibodies (mAbs) provide an option for the prevention and treatment of ZIKV infection. Previous studies identified a potent neutralizing human mAb ZIKV-117 that reduced fetal infection and death in mice following ZIKV challenge. In this study, we report exquisite potency of ZIKV-117-LALA-YTE, which has been engineered to reduce Fc receptor binding and to extend half-life, in a titration study in rhesus macaques to protect against ZIKV challenge. We show complete protection at a dose of 0.016 mg/kg ZIKV-117-LALA-YTE, which resulted in median serum concentrations of 0.13 µg/mL. The high potency of this mAb supports its potential clinical development as a novel biotherapeutic intervention for ZIKV.IMPORTANCEIn this study, we report the potency of the Zika virus (ZIKV)-specific neutralizing antibody ZIKV-117-LALA-YTE against ZIKV challenge in a titration study rhesus macaques. This high potency supports the further development of this monoclonal antibody for ZIKV.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0142924"},"PeriodicalIF":4.0,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11650990/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142639244","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":"Minute virus of mice NS1 redirects casein kinase 2 specificity to suppress the ATR DNA damage response pathway during infection.","authors":"Igor Etingov, David J Pintel","doi":"10.1128/jvi.00559-24","DOIUrl":"10.1128/jvi.00559-24","url":null,"abstract":"<p><p>During infection the autonomous parvovirus minute virus of mice (MVM) generates extensive DNA damage which facilitates virus replication and induces a cellular DNA damage response (DDR) driven by the ataxia telangiectasia mutated (ATM) kinase. Atypically, the ataxia telangiectasia and Rad-3-related (ATR) DDR pathway remains inactive. Upon DNA damage ATR is normally recruited to single-stranded DNA sequences formed at genomic DNA damage sites, and while within a multiprotein complex activates, via phosphorylation, the key DDR regulator checkpoint kinase 1 (Chk1). Inactivation of ATR during MVM infection leads to the accumulation of damaged DNA and enhancement of virus replication. Although ATR is inactivated, we show that during infection, the Chk1 activation pathway downstream of the initial ATR activating events remained functional. Activation of ATR, and consequently of Chk1, requires interaction with TopBP1, which itself is maintained in proximity to ATR by interaction with the phosphorylated S387 residue of Rad9, part of the Rad9-Hus1-Rad1 (911) complex. Both MVM infection and MVM NS1 overexpression inhibited Rad9 S387 phosphorylation and subsequent ATR activation. ATR inactivation during infection was suppressed by expression of Rad9 bearing a phosphomimetic 387 residue, indicating that this site, and the function it served, was the target of NS1 inhibition. NS1 interaction with CK2α and CK2α enzymatic activity was both required to prevent ATR activation, indicating MVM retargeted this kinase's activity during infection. Inhibition of the protein phosphatase 2C (PP2C) prevented Rad9 S387 dephosphorylation and Chk1 inactivation during MVM infection and NS1 overexpression revealing its role in the pathway's suppression.</p><p><strong>Importance: </strong>Infection by the parvovirus minute virus of mice (MVM) causes significant DNA damage and induces a potent DNA damage response (DDR) which the virus exploits to further its replication. The cell responds to infection with an ATM-regulated DDR; however, atypically, the ATR-regulated DDR pathway is disabled during infection. This prevents Chk1 activation, thus allowing the accumulation of damaged DNA which facilitates virus replication. We describe here how MVM, and specifically the main viral replication protein NS1, inhibits ATR activation. Activation of ATR, and consequently Chk1, requires TopBP1 localization into the activating complex via its interaction with a phosphorylated residue of Rad9. We show that NS1 redirects casein kinase 2 to activate a phosphatase in the PP2C family which causes dephosphorylation of this critical residue, thus inhibiting ATR activation. This work provides mechanistic insight into one of the ways by which parvoviruses modify the host DDR response to facilitate their replication.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0055924"},"PeriodicalIF":4.0,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11650992/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142676061","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":"Fish <i>Snx27</i> promotes viral products by modulating the innate immune response and exosomal machinery.","authors":"Yepin Yu, Jiaxin Liu, Zhiwen Zhao, Xiaoming Lan, Linmiao Li, Junjie Hu, Ying-An Zang, Xiujuan Zhang, Jinping Chen","doi":"10.1128/jvi.00974-24","DOIUrl":"10.1128/jvi.00974-24","url":null,"abstract":"<p><p>Viral nervous necrosis caused by the nervous necrosis virus (NNV) poses a significant threat to the global aquaculture industry. Developing preventive methods to minimize economic losses due to NNV infections is crucial. This study explored the role of the sorting nexin 27 (<i>Snx27</i>) gene, encoded by the orange-spotted grouper (<i>Epinephelus coioides</i>) and referred to as <i>EcSnx27</i>, as an immune regulator affecting red-spotted grouper nervous necrosis virus (RGNNV) infection <i>in vitro</i>. Our findings revealed that <i>EcSnx27</i> negatively regulates interferon (IFN)-related cytokines and the promoter activities of fish ISRE and NF-κB. Furthermore, we identified the SNX-FERM and SNX-FERM-like domains as responsible for the interaction between <i>EcSnx27</i> and RGNNV coat protein. Through the detection of viable virions associated with <i>EcSnx27</i>-containing exosomes, we propose that <i>EcSnx27</i> may contribute to the release process of RGNNV by influencing the apoptosis-linked gene 2-interacting protein X (ALIX)-associated exosomal pathway. Consequently, our study suggests that <i>EcSnx27</i> promotes RGNNV replication by inhibiting the IFN immune response and facilitating virus production and release through ALIX-mediated exosomal machinery.IMPORTANCERed grouper nervous necrosis virus (RGNNV), a member of the <i>Nodaviridae</i> family, has emerged as a significant cause of fish diseases worldwide, leading to high morbidity and mortality rates. This study investigated the sorting nexin 27 (<i>Snx27</i>) gene encoded by the orange-spotted grouper (<i>Epinephelus coioides</i>) on RGNNV infection in grouper kidney cells. Our findings revealed that <i>EcSnx27</i> negatively regulated the interferon pathway, resulting in the promotion of RGNNV replication. Additionally, we observed that <i>EcSnx27</i> could interact with apoptosis-linked gene 2-interacting protein X (ALIX) and the RGNNV coat protein, suggesting its potential involvement in viral release processes through modulation of the exosomal pathway. Our study identified <i>EcSnx27</i> as a key target that RGNNV exploits to enhance viral production. This finding offers valuable insights into the immune evasion and viral release mechanisms of non-enveloped RNA viruses.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0097424"},"PeriodicalIF":4.0,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11650975/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142569054","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":"Correction for Huang and Zhang, \"Functional Analysis of a Crustacean MicroRNA in Host-Virus Interactions\".","authors":"Tianzhi Huang, Xiaobo Zhang","doi":"10.1128/jvi.01710-24","DOIUrl":"10.1128/jvi.01710-24","url":null,"abstract":"","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0171024"},"PeriodicalIF":4.0,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11650991/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142569051","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":"No evidence that mutations in SARS-CoV-2 variants of concern derive from homologous fragments in gut microbiota.","authors":"Rhys H Parry, Spyros Lytras, Mary E Petrone, Michelle Wille, Alexander Crits-Christoph, Robert J Gifford, Akatsuki Saito, Teemu Smura, Thomas P Peacock","doi":"10.1128/jvi.01468-24","DOIUrl":"10.1128/jvi.01468-24","url":null,"abstract":"<p><p>Understanding the origin and evolution of mutations in SARS-CoV-2 variants of concern (VOCs) is a critical area of research. B. Cao, X. Wang, W. Yin, Z. Gao, and B. Xia (mBio 15:e03187-23, 2024, https://doi.org/10.1128/mbio.03187-23) proposed that these mutations originated from bacterial sequences incorporated into the viral genome through stochastic template-switching by the viral RNA-dependent RNA polymerase (RdRp). Their analysis suggested that 62% of the viral mutation fragments (VMFs) in key SARS-CoV-2 proteins were identical to bacterial protein sequences. Given the implications of this finding, we re-examined the methods employed and argue that they resulted in false-positive findings. Specifically, the short query length of VMFs, seven amino acids, leads to spurious matches in large protein databases, as indicated by high BLAST Expect values. Furthermore, we analyzed the nucleotide sequence of VMFs, revealing no unique homology between SARS-CoV-2 and bacterial sequences. Consequently, the evidence does not support the hypothesis that bacterial sequences contribute to the evolution of SARS-CoV-2 VOCs. Instead, the emergence of these variants is more plausibly attributed to factors intrinsic to viral replication and evolution, such as the error-prone nature of RdRp, intrahost diversity, and recombination of related viral sublineages.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0146824"},"PeriodicalIF":4.0,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11650967/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142569073","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}