Journal of Virology最新文献

{"title":"Galectin 3-binding protein suppresses PRRSV replication via Cullin3-mediated ubiquitination degradation of non-structural protein 12.","authors":"Xinrong Wang, Wenli Zhang, Juan Zhang, Rui Li, Longxiang Zhang, Nan Yan, Junhai Zhu, Lizhi Fu, Yue Wang","doi":"10.1128/jvi.01083-25","DOIUrl":"https://doi.org/10.1128/jvi.01083-25","url":null,"abstract":"<p><p>Porcine reproductive and respiratory syndrome virus (PRRSV) poses a major threat to the global swine industry, yet effective antiviral strategies remain limited. This study identifies galectin 3-binding protein (LGALS3BP) as a critical host factor inhibiting PRRSV infection through targeting the viral conserved non-structural protein 12 (nsp12), a key component of the viral replication-transcription complex. Overexpression of LGALS3BP significantly suppressed PRRSV replication, while its knockdown enhanced viral replication. Mechanistically, LGALS3BP recruits the Cullin3 E3 ubiquitin ligase via its BACK domain to mediate the ubiquitination of nsp12 at lysine residue 91, leading to proteasomal degradation. This process disrupts nsp12-dependent synthesis of viral subgenomic RNA, thereby disrupting replication. Additionally, LGALS3BP enhances antiviral innate immunity by upregulating interferon (IFN)-β and IFN-stimulated genes (ISGs). The antiviral effect of LGALS3BP is conserved across diverse PRRSV strains, highlighting its broad-spectrum potential. These findings reveal a dual mechanism whereby LGALS3BP restricts PRRSV through direct degradation of a critical viral enzyme and modulation of host immune responses, highlighting LGALS3BP as a promising therapeutic avenue for PRRSV control.IMPORTANCEPorcine reproductive and respiratory syndrome virus (PRRSV) remains a major challenge to global swine production due to its genetic diversity, rapid mutation rate, and ability to evade host immunity. The nsp12 is highly conserved across PRRSV strains and plays a crucial role in viral RNA synthesis. This study identifies LGALS3BP as a critical host factor that inhibits PRRSV infection by targeting nsp12 via the ubiquitin-proteasome pathway. By uncovering this novel antiviral mechanism, the research highlights LGALS3BP as a promising therapeutic target for PRRSV control. Moreover, it contributes to our understanding of how host factors modulate viral replication and immunity, opening new avenues for developing host-targeted antiviral strategies. These findings have the potential to mitigate PRRSV-driven economic losses and improve swine health worldwide.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0108325"},"PeriodicalIF":3.8,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145292691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Virion aggregation shapes infection dynamics and evolutionary potential.","authors":"Meher Sethi, David VanInsberghe, Bernardo A Mainou, Anice C Lowen","doi":"10.1128/jvi.01137-25","DOIUrl":"https://doi.org/10.1128/jvi.01137-25","url":null,"abstract":"<p><p>Viral spread is classically thought to be mediated by single viral particles. However, viruses can also disseminate as aggregates, inside membranous vesicles, and as clusters bound to bacterial or complex surfaces. The implications of collective dispersal for viral infectivity and evolution remain incompletely defined. Here, we used mammalian orthoreovirus to evaluate the impact of aggregation on the propagation of infection and the generation of viral diversity through reassortment. Aggregation of free virions was induced by manipulating pH and ionic conditions. This treatment promoted coordinated delivery of viruses to cells, increasing the number of virions per infected cell and the number of virions per occupied endosome at early times of infection. Likely due to a consolidation of infectious units, aggregation concomitantly reduced the overall infectivity of the viral population and progeny virus yields. When viral populations comprised two genetically distinct viruses, aggregation increased the frequency of mixed infection and genetic exchange through reassortment. Thus, the formation of collective infectious units lowers the replicative potential of mammalian orthoreovirus populations but increases viral evolutionary potential by promoting genetic diversification.IMPORTANCEA deeper understanding of the processes shaping viral evolution will advance our ability to anticipate viral emergence, escape from immune responses, and resistance to therapeutics. Although much is known about how genetic variation fuels viral evolution, how modes of viral spread influence the generation and structure of genetic variation remains poorly characterized. Here, we examine how the collective dissemination of viruses modulates early infection dynamics and viral diversity. We find that, although infection in groups reduces the number of independently infected cells, it results in a more genetically diverse progeny population, an outcome that may enhance evolutionary potential.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0113725"},"PeriodicalIF":3.8,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145292692","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative analysis of NSP5/VP2-induced viroplasm-like structures in rotavirus species A to J.","authors":"Ariana Cosic, Melissa Lee, Kurt Tobler, Claudio Aguilar, Cornel Fraefel, Catherine Eichwald","doi":"10.1128/jvi.00990-25","DOIUrl":"https://doi.org/10.1128/jvi.00990-25","url":null,"abstract":"<p><p>Rotavirus (RV) is classified into nine species, A-D and F-J, with RV species A (RVA) being the most extensively studied. While RVA infects infants and young animals, non-RVA species infect adult humans, various mammals, and birds. However, the lack of appropriate research tools has limited our understanding of non-RVA life cycles. RVA replication and assembly occur in cytosolic inclusions termed viroplasms. We recently identified viroplasm-like structures (VLS) composed of NSP5 and NSP2 in non-RVA. In this context, globular VLS induced by NSP2 formed in RVA, RVB, RVD, RVF, RVG, and RVI, but not in RVC, RVH, and RVJ. Additionally, in RVA, VLS can also be formed through the co-expression of NSP5 with VP2. Here, we report that VP2-induced VLS formed in RV species A to J, with notable formation in RVH and RVJ, where NSP2 RVH or RVJ was also recruited into VLSs. The NSP5 C-terminal region in non-RVA is required for association with VP2 and forming VLS. Mutation of conserved VP2-L124 in RVA to alanine disrupts viroplasm formation, impairing RV replication. Equivalent residues within the same predicted VP2 region disrupt VLS formation across non-RVA. We also observed interspecies VLS formation, most notably between the closely related pairs RVA-RVC, RVH-RVJ, and RVD-RVF. Interestingly, substituting the N-terminal region of VP2 from RVB with that of VP2 from RVG supported VLS formation with NSP5 from RVB in avian cells. Elucidating the formation of viroplasms is essential for developing strategies to halt infection across RV species A to J.</p><p><strong>Importance: </strong>Rotaviruses (RV) are a group of viruses classified into species A through J, with species A being the best understood. Other RV species infecting animals and humans are less studied due to limited research tools. In RVA, the virus replicates in specialized compartments called viroplasms formed in the cytoplasm by viral proteins, including NSP5, NSP2, and VP2. In this study, we explored how similar structures, termed viroplasm-like structures (VLS), are formed by proteins of RV species A-J. We found that for all tested RV species, NSP5 and VP2 form VLSs. We also identified key regions in the VP2 protein that are essential for forming these structures. Understanding how viroplasms form across different RV species may help develop new strategies to block infection in humans and animals.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0099025"},"PeriodicalIF":3.8,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145286388","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-base m⁶A epitranscriptomics reveals novel HIV-1 host interaction targets in primary CD4⁺ T cells.","authors":"Siyu Huang, Yutao Zhao, Stacia Phillips, Julia E Warrick, Michael G Kearse, Chuan He, Li Wu","doi":"10.1128/jvi.01536-25","DOIUrl":"https://doi.org/10.1128/jvi.01536-25","url":null,"abstract":"<p><p><i>N</i>⁶-methyladenosine (m⁶A) plays a critical role in regulating RNA Ostability, localization, and gene expression. m⁶A modification is also important for modulating the expression of viral and cellular genes during HIV-1 infection. However, the function of m⁶A modification in regulating HIV-1 infection of primary CD4⁺ T cells remains unclear. Here, we demonstrate that HIV-1 infection of activated primary CD4⁺ T cells promotes the interaction between the m⁶A writer complex subunits methyltransferase-like 3 and 14 (METTL3/METTL14). Using single-base m⁶A-specific RNA sequencing, we identified differentially m⁶A-modified cellular mRNAs in HIV-1-infected primary CD4⁺ T cells, including <i>perilipin 3</i> (<i>PLIN3</i>). We also identified 30 m⁶A sites in HIV-1 RNA from infected primary CD4⁺ T cells. HIV-1 infection increased <i>PLIN3</i> mRNA level and nuclear accumulation but decreased PLIN3 protein expression in primary CD4⁺ T cells. Polysome profiling revealed that <i>PLIN3</i> mRNA was less actively translated during HIV-1 infection of primary CD4⁺ T cells. Furthermore, PLIN3 knockdown in primary CD4⁺ T cells significantly reduced HIV-1 release but enhanced virion infectivity. Our results highlight the importance of m⁶A RNA modification during HIV-1 infection and suggest PLIN3 as a regulatory protein of HIV-1 replication in primary CD4⁺ T cells.IMPORTANCEm⁶A is a common chemical modification on mRNA that regulates RNA stability, localization, and gene expression. m⁶A modification of viral and cellular RNA is important for HIV-1 infection. We found that HIV-1 infection of primary CD4⁺ T cells promotes the interaction between the m⁶A writer complex subunits that add m⁶A modification. Using m⁶A-specific RNA sequencing, we identified several cellular mRNAs with altered m⁶A modifications during HIV-1 infection, including <i>PLIN3</i>. Interestingly, HIV-1 infection increased <i>PLIN3</i> mRNA levels and nuclear localization but reduced PLIN3 protein expression in primary CD4⁺ T cells. When we knocked down PLIN3 in primary CD4⁺ T cells, it decreased HIV-1 release but made the HIV-1 more infectious. Our findings show the importance of m⁶A RNA modification in HIV-1 infection by regulating host genes like <i>PLIN3</i> and suggest a unique regulatory mechanism in HIV-1-infected primary CD4⁺ T cells.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0153625"},"PeriodicalIF":3.8,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145286385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nephropathogenic infectious bronchitis virus induces epithelial-mesenchymal transition of renal tubular epithelial cells through the TGF-β/p-P38 pathway causing uric acid excretion disorder in chickens.","authors":"Yunfeng Chen, Yan Shi, Cheng Huang, Haoyu Huang, Yizhou Zeng, Gaofeng Cai, Zhanhong Zheng, Ping Liu, Xiaona Gao, Xiaoquan Guo","doi":"10.1128/jvi.01031-25","DOIUrl":"https://doi.org/10.1128/jvi.01031-25","url":null,"abstract":"<p><p>Nephropathogenic infectious bronchitis virus (NIBV) infection usually causes kidney enlargement and urate deposition in chickens, leading to sudden death. However, the mechanism by which NIBV causes urate deposition in the kidneys has not yet been elucidated. The coordinated operation of uric acid transporters is crucial for the kidneys to maintain uric acid homeostasis, and existing studies have shown that the occurrence of cell epithelial-mesenchymal transition (EMT) can affect the expression of uric acid transporters. Thus, this study aimed to explore the effect of NIBV on urate transporters and elucidate the mechanism of EMT in NIBV-induced urate deposition in chicken kidneys <i>in vivo</i> and <i>in vitro</i>. The results revealed that NIBV infection led to an abnormal increase in uric acid levels in chicks, affected the expression of uric acid transport proteins, induced EMT in renal tubular epithelial cells, and activated the TGF-β/p-p38 pathway. The changes in uric acid concentration induced by NIBV were related to the uric acid excretion protein ABCG2, whose expression is negatively regulated by EMT. The occurrence of NIBV-induced EMT coincided with the time point at which NIBV activated the TGF-β/p-p38 pathway. After siRNA knockdown of p38 MAPK, EMT did not occur, and ABCG2 expression returned to normal. In summary, the mechanism by which NIBV causes abnormal elevation of uric acid levels in chickens is through the induction of EMT in renal tubular epithelial cells via the TGF-β/p-p38 pathway, which strongly inhibits the expression of ABCG2, thereby causing uric acid excretion disorders in chickens.IMPORTANCENIBV infection results in a reduction in uric acid transporter expression in the kidneys of chickens. ABCG2 plays a pivotal role in the excretion of uric acid in chickens. The mechanism by which NIBV causes an abnormal increase in uric acid levels in chickens involves the induction of renal tubular epithelial cell EMT through the TGF-β/P-p38 pathway and the subsequent strong inhibition of ABCG2 expression, causing uric acid excretion disorders in chickens.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0103125"},"PeriodicalIF":3.8,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145286339","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interferon alpha-inducible protein 27 (IFI27) inhibits hepatitis B virus (HBV) transcription through downregulating cellular transcription factor C/EBPα.","authors":"Xiaoyang Yu, Cheng-Der Liu, Sheng Shen, Elena S Kim, Zhentao Liu, Hu Zhang, Ning Sun, Yuanjie Liu, Pia M Martensen, Yufei Huang, Haitao Guo","doi":"10.1128/jvi.01509-25","DOIUrl":"https://doi.org/10.1128/jvi.01509-25","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Interferon alpha (IFNα) is the only approved immunomodulatory drug for chronic hepatitis B treatment, exerting its antiviral effects through the induction of interferon-stimulated genes (ISGs). To identify key antiviral ISGs that inhibit hepatitis B virus (HBV) replication, we performed transcriptome analysis of IFNα-treated HepG2-NTCP cells and found that IFI27 was among the most differentially expressed genes. The high inducibility of IFI27 by IFNα was further validated in primary human hepatocytes. Overexpression of IFI27 significantly suppressed HBV replication in both HBV-transfected and -infected cells, primarily by reducing HBV RNA transcription. Conversely, IFI27 knockdown markedly diminished the antiviral effect of IFNα in HBV-infected cells. IFI27 is predominantly localized in the cytoplasm, and RNA-seq analysis revealed that IFI27 inhibits HBV transcription without drastically altering the host transcriptome, indicating that IFI27 does not inhibit HBV transcription directly or through altering the transcription of cellular transcription factors or inducing antiviral signaling pathways. Instead, we found that IFI27 suppresses HBV transcription by promoting the ubiquitination-dependent proteasomal degradation of C/EBPα in the cytoplasm, a cellular transcription factor critical for HBV RNA transcription. Further investigation identified the E3 ubiquitin ligase SKP2 as a key mediator of this process, facilitating IFI27-induced C/EBPα ubiquitination and degradation. Notably, SKP2 knockdown abrogated IFI27's antiviral activity against HBV. Taken together, our findings reveal that IFI27 contributes to IFNα-mediated antiviral activity against HBV by targeting C/EBPα for SKP2-dependent ubiquitination and proteasomal degradation. This study thus sheds new light on the antiviral mechanism of IFNα-based therapy for chronic hepatitis B.IMPORTANCEChronic hepatitis B virus (HBV) infection affects approximately 250 million people worldwide with limited treatment options. Interferon alpha (IFNα) remains the only approved immunomodulatory treatment for chronic hepatitis B, working in HBV-infected liver cells through inducing antiviral genes. To identify key interferon-inducible genes involved in HBV suppression, we performed transcriptome analysis of IFNα-treated liver cells and identified IFI27 as one of the most upregulated genes. Functional studies demonstrated that IFI27 inhibits HBV replication by reducing viral RNA transcription, and its knockdown significantly impaired the antiviral effect of IFNα. Mechanistically, IFI27 suppresses HBV transcription by promoting the ubiquitin-proteasome-mediated degradation of C/EBPα, a transcription factor critical for HBV RNA synthesis. This process is dependent on the E3 ubiquitin ligase SKP2, as SKP2 knockdown abolished IFI27-mediated antiviral activity. These findings reveal IFI27 as a critical mediator of IFNα-induced antiviral responses against HBV and provide new insights into host-directed antivira","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0150925"},"PeriodicalIF":3.8,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145280472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A conserved RNA structure at the capsid-coding sequence of Zika virus genome is required for viral replication in a host-dependent manner.","authors":"Guadalupe S Costa Navarro, Horacio M Pallarés, María Mora González López Ledesma, Luana de Borba, Romina Mazzolenis, Andrea V Gamarnik","doi":"10.1128/jvi.01550-25","DOIUrl":"https://doi.org/10.1128/jvi.01550-25","url":null,"abstract":"<p><p>Flaviviruses are emerging and re-emerging pathogens causing widespread epidemics worldwide. Their RNA genomes play multiple roles during infection, folding into dynamic structures that regulate viral processes. To understand the mechanisms of flavivirus infection and to design genetic tools for viral countermeasures, it is important to dissect functional RNA structures present in viral genomes. Here, we investigate RNA structures within the open reading frame of the Zika virus (ZIKV) genome that regulate viral replication. We identified a functional stem-loop structure, SL1, located within the conserved C1 element in the capsid protein coding sequence of mosquito-borne flavivirus genomes. The integrity of the SL1 structure was crucial for viral RNA amplification in mosquito cells and enhanced ZIKV replication in vertebrate cells. Evolution experiments in mosquito cells with lethal SL1-disrupting mutants revealed reversions and pseudo-reversions that restored SL1 structure, confirming its role as a cis-acting RNA element. We also found that a sequence within SL1 contributes to a novel genome cyclization element unique to ZIKV. This sequence folds locally into SL1 or hybridizes with a 3' UTR sequence to extend the conserved cyclization sequence (CS1), which is known to be essential for RNA synthesis. Although the C1 element is conserved among mosquito-borne flaviviruses, the RNA structures and long-range interactions in this element required for ZIKV replication differ from those reported for dengue virus. Our studies highlight the presence of a conserved RNA element operating through distinct mechanisms in related flaviviruses. These findings offer insights into the dynamic nature of the ZIKV genome and provide information for rational flavivirus attenuation.</p><p><strong>Importance: </strong>Flaviviruses are important human pathogens mainly vectored by arthropods. They contain RNA genomes that fold into complex structures with biological functions in viral infection. Zika virus is a flavivirus that has caused significant outbreaks and epidemics around the world. In this study, we used Zika virus to identify functional RNA structures present in the viral coding sequence. We manipulated an infectious clone from an Argentinean Zika virus isolate to dissociate protein-coding sequences from cis-acting RNA structures and discovered an RNA element in the capsid coding region that is essential for Zika virus replication in mosquito cells. Point mutations, disrupting the identified structure, impaired infection in mosquito cells and rendered viral attenuation in mammalian cells. Selection of revertant viruses in cell culture restored the RNA structure and the viral replication capacity. Our studies provide a basic understanding of the flavivirus genome organization, which is necessary for designing rational antiviral strategies.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0155025"},"PeriodicalIF":3.8,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145280249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CLL, together with C1qR, suppresses WSSV infection by regulating the activation of Dorsal.","authors":"Xiao-Tong Cao, Lian-Jie Wu, Jia-Yu Si, Xian-Wei Wang, Jiang-Feng Lan","doi":"10.1128/jvi.00416-25","DOIUrl":"https://doi.org/10.1128/jvi.00416-25","url":null,"abstract":"<p><p>There is no evidence that arthropods possess a complement system. In arthropods, only gC1qR has been reported. The functional convergence of gC1qR in arthropods and vertebrates during evolution remains to be further elucidated. In the present study, a C-type lectin named <i>Pc</i>CLL, which contains a C1q-like sequence (a segment of the C1q globular head) and might be involved in antiviral immunity, was identified in <i>Procambarus clarkii</i>. When crayfish are infected with white spot syndrome virus (WSSV), some C1qRs (gC1qR homologs), which are located at the cell membrane, recognize WSSV by interacting with the envelope protein VP28. Subsequently, C1qR recruits <i>Pc</i>CLL in the cell, and the C1qR-<i>Pc</i>CLL complexes synergistically promote the nuclear translocation of Dorsal. Serine-arginine protein kinase (SRPK) is an essential molecule in this process. The C1qR<i>-Pc</i>CLL-SRPK axis regulates the activation and translocation of Dorsal. Finally, the C1qR<i>-Pc</i>CLL-Dorsal axis can promote resistance to WSSV infection by regulating the expression of the lectin-like protein (<i>Pc</i>LT). In both vertebrates and arthropods, C1qR appears to participate in antiviral immunity, but the mechanisms were different. This may highlight a fascinating evolutionary trajectory across animals.</p><p><strong>Importance: </strong>The body's recognition of pathogenic microorganisms plays an important role in host resistance to pathogen infection. Here, we identified a lectin, <i>Pc</i>CLL, in the red swamp crayfish <i>Procambarus clarkii</i>, which contains a C1q-like sequence and might be involved in antiviral immunity. C1qR located on the cell membrane can recognize white spot syndrome virus by interacting with VP28. Then, it recruits <i>Pc</i>CLL and promotes the nuclear translocation of Dorsal. This process cannot be achieved without SRPK, which is a splicing regulator that can phosphorylate proteins. CLL (C1q-like motif that is part of the globular head of C1q) and C1qR (gC1qR homolog) interact with each other, and they are involved in the antiviral immune response by activating Dorsal. This may be a new mechanism for the host to recognize pathogens.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0041625"},"PeriodicalIF":3.8,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145280507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spike mutations that affect the function and antigenicity of recent KP.3.1.1-like SARS-CoV-2 variants.","authors":"Bernadeta Dadonaite, Sheri Harari, Brendan B Larsen, Lucas Kampman, Alex Harteloo, Anna Elias-Warren, Helen Y Chu, Jesse D Bloom","doi":"10.1128/jvi.01423-25","DOIUrl":"https://doi.org/10.1128/jvi.01423-25","url":null,"abstract":"<p><p>SARS-CoV-2 is under strong evolutionary selection to acquire mutations in its spike protein that reduce neutralization by human polyclonal antibodies. Here, we use pseudovirus-based deep mutational scanning to measure how mutations to the spike from the recent KP.3.1.1 SARS-CoV-2 strain affect cell entry, binding to the ACE2 receptor, RBD up/down motion, and neutralization by human sera and clinically relevant antibodies. The spike mutations that most affect serum antibody neutralization sometimes differ between sera collected before versus after recent vaccination or infection, indicating that these exposures shift the neutralization immunodominance hierarchy. The sites where mutations cause the greatest reduction in neutralization by post-vaccination or infection sera include receptor-binding domain (RBD) sites 475, 478, and 487, all of which have mutated in recent SARS-CoV-2 variants. Multiple mutations outside the RBD affect sera neutralization as strongly as any RBD mutations by modulating the RBD up/down movement. Some sites that affect RBD up/down movement have mutated in recent SARS-CoV-2 variants. Finally, we measure how spike mutations affect neutralization by three clinically relevant SARS-CoV-2 antibodies: VYD222, BD55-1205, and SA55. Overall, these results illuminate the current constraints and pressures shaping SARS-CoV-2 evolution and can help with efforts to forecast possible future antigenic changes that may impact vaccines or clinical antibodies.IMPORTANCEThis study measures how mutations to the spike of a SARS-CoV-2 variant that circulated in early 2025 affect its function and recognition by both the polyclonal antibodies produced by the human immune system and monoclonal antibodies used as prophylactics. These measurements are made with a pseudovirus system that enables safe study of viral protein mutations using virions that can only infect cells once. The study identifies mutations that decrease recognition by current human antibody immunity; many of these mutations are increasingly being observed in new viral variants. It also shows the importance of mutations that move the spike's receptor-binding domain up or down. Overall, these results are useful for forecasting viral evolution and assessing which newly emerging variants have reduced recognition by immunity and antibody prophylactics.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0142325"},"PeriodicalIF":3.8,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145280491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protein-S-nitrosylation of adenovirus-5 E1A and human papillomavirus 16 E7 limits their ability to inhibit STING activity.","authors":"Justin B Cox, Eain A Murphy","doi":"10.1128/jvi.01456-25","DOIUrl":"https://doi.org/10.1128/jvi.01456-25","url":null,"abstract":"<p><p>All viruses that establish successful infections express proteins that inhibit innate anti-viral pathways such as the stimulator of interferon genes (STING) pathway. In response, cells have evolved mechanisms to limit viruses by modifying these viral proteins via post-translational modifications (PTMs). One potent PTM, protein-S-nitrosylation, inhibits the ability of human cytomegalovirus (HCMV) to undermine the establishment of an anti-viral state. The direct nitrosylation of HCMV tegument protein pp71 at a central cysteine within its pRB binding domain reduces pp71's ability to limit the activity of STING. Two different proteins encoded by unrelated DNA viruses, adenovirus (AdV) E1A and human papillomavirus (HPV) E7, also contain a pRB binding domain and inhibit STING like pp71. Herein, we report that E1A and E7 are both protein-S-nitrosylated like pp71. Stable cell lines expressing a WT, or mutants in which the predicted modified cysteine was changed to the closely related serine amino acid, thus blocking protein-S-nitrosylation, revealed that E1A and E7 are both protein-S-nitrosylated. Furthermore, induction of the STING pathway promoted IFN-β1 transcript production and the phosphorylation of IRF3, which was limited in E1A and E7 stable cell lines. Mutant stable cell lines exhibited a stronger inhibition of IFN-β1 transcription and reduced IRF3 phosphorylation, suggesting that the PTM limits WT viral protein inhibition of STING. Furthermore, both E1a and E7 can complement the replication of a HCMV that lacks pp71 during times of STING activation. These observations support a model in which protein-S-nitrosylation of viral virulence factors may function as an anti-viral mechanism in DNA virus infections.IMPORTANCEDNA viruses, such as HCMV, AdV, and HPV, have the capacity to cause significant disease. Infection with AdV can cause severe lower respiratory and liver disease in children, and HPV infection is persistent and is a causative agent of cancer. Thus, these infections can be a severe health risk. Host cells have adapted innate responses like protein S-nitrosylation to limit viral replication. Our previous work reported that direct nitrosylation of two HCMV viral proteins, pp65 and pp71, limits their ability to undermine host anti-viral responses. Herein, we investigated whether protein-S-nitrosylation of AdV and HPV proteins inhibits their functions, suggesting that this PTM is an anti-viral mechanism. This may provide insight into the development of broad anti-viral therapeutics for persistent viral infections.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0145625"},"PeriodicalIF":3.8,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145280514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}