Virologica Sinica最新文献

{"title":"ASFV pA137R protein triggers inflammatory response by inducing NF-κB signaling pathway and facilitating NLRP3 inflammasome assembly","authors":"Yi Zeng,&nbsp;Xiaohong Liu,&nbsp;Siqi Dong,&nbsp;Hanyu Wu,&nbsp;Li Huang,&nbsp;Changjiang Weng","doi":"10.1016/j.virs.2026.05.008","DOIUrl":"10.1016/j.virs.2026.05.008","url":null,"abstract":"<div><div>African swine fever (ASF), caused by the African swine fever virus (ASFV), is characterized by high mortality in infected pigs. ASFV infection triggers severe inflammatory response in the host, which is a crucial contributor to the high lethality of this disease. However, the underlying mechanism by which ASFV infection induces inflammatory response is still poorly understood. In this study, we found that UV-inactivated ASFV induces interleukin-1β (IL-1β) production, suggesting that certain structural proteins incorporated in the virion possess the ability to trigger inflammatory response. Further investigations demonstrated that deletion of the ASFV <em>A137R</em> gene significantly inhibited the ASFV-induced upregulation of the mRNA transcription of various proinflammatory genes and phosphorylation of p65 and IκBα. Furthermore, the purified pA137R protein promoted the mRNA transcription of these proinflammatory genes and phosphorylation of p65 and IκBα. Additionally, pA137R protein interacted with the NACHT and LRR domains of NLRP3 through its N terminal 1–99 amino acid domain, thereby promoting the oligomerization of NLRP3 and ASC and subsequently facilitating NLRP3 inflammasome assembly. Collectively, our findings identify ASFV pA137R protein as a key proinflammatory determinant of ASFV, which not only advances our understanding of the molecular mechanisms underlying ASFV-induced inflammatory response but also provides new insights into ASFV pathogenesis.</div></div>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"41 3","pages":"Pages 602-611"},"PeriodicalIF":4.7,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148101922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dominant HA motif 131/132-NT shapes the phenotype of avian H9N2 influenza virus by modulating agglutination property, receptor specificity and infectivity in animals","authors":"Xue Chen,&nbsp;Jinze Dong,&nbsp;Chuankuo Zhao,&nbsp;Linlin Wang,&nbsp;Xinyang Gao,&nbsp;Zhixin Li,&nbsp;Honglei Sun,&nbsp;Yipeng Sun,&nbsp;Jinhua Liu,&nbsp;Rui Zhang,&nbsp;Juan Pu","doi":"10.1016/j.virs.2026.06.007","DOIUrl":"10.1016/j.virs.2026.06.007","url":null,"abstract":"<div><div>H9N2 avian influenza viruses (AIVs), which are enzootic in poultry and possess spillover potential to humans, represent a considerable global public health threat. Since 2021, we have observed an unprecedented decline in the ability of H9N2 viruses to agglutinate chicken red blood cells (CRBCs), a change that impairs effective detection in routine surveillance. Substituting CRBCs with turkey or guinea pig erythrocytes in hemagglutination assays effectively restored virus detectability. Through integrated bioinformatic and biological approaches, we identified that this phenotype is associated with specific amino acid substitutions at residues 131 and 132 of the 130-loop in the hemagglutinin (HA) protein. The HA motif 131/132-NT emerged in 2015 and rapidly increased in frequency, becoming the dominant pattern since 2021 in chickens and humans. Critically, the 131/132-NT motif attenuated viral binding affinity to short-chain α2,6-linked sialic acid receptors, explaining the loss of agglutination with CRBCs. Animal experiments further demonstrated that viruses carrying the HA 131/132-NT mutations maintained strong infectivity in chickens but altered tissue tropism in mice, showing reduced replication in the lungs. Collectively, our findings reveal a potential surveillance gap caused by reduced hemagglutination activity of H9N2 viruses, which may compromise the sensitivity of CRBC-based detection and potentially lead to under-detection of circulating viruses. Incorporating turkey or guinea pig red blood cells into surveillance protocols is therefore recommended to enhance detection sensitivity.</div></div>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"41 3","pages":"Pages 624-637"},"PeriodicalIF":4.7,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148253565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"EV-A71 induces GSDME-dependent T-cell pyroptosis: A novel mechanism and MeCbl therapeutic potential","authors":"Chong Wang,&nbsp;Bingyu Guo,&nbsp;Yilin Li,&nbsp;Xi Zhou,&nbsp;Zongqiang Cui,&nbsp;Yujie Ren","doi":"10.1016/j.virs.2026.05.006","DOIUrl":"10.1016/j.virs.2026.05.006","url":null,"abstract":"<div><div>Enterovirus A71 (EV-A71) is the primary pathogen causing severe hand-foot-and-mouth disease (HFMD) in young children, with T-cell immune dysfunction closely linked to severe clinical outcomes. However, the molecular mechanisms underlying EV-A71-mediated T-cell impairment remain unclear, and no specific therapies are currently available. Here, we investigated the interaction between EV-A71 and T cells, and explored potential targeted therapeutic strategies. Our results showed that EV-A71 efficiently infects T cell lines (Jurkat, EL-4) and primary mouse CD3⁺ T cells in a dose- and time-dependent manner, inducing T-cell death and upregulating pro-inflammatory cytokines (IL-1β, IL-6, TNF-α). Mechanistically, EV-A71 infection triggers GSDME-dependent pyroptosis in T cells via caspase-3 activation, rather than GSDMD-dependent pyroptosis, as evidenced by genetic ablation and inhibitor experiments. Methylcobalamin (MeCbl), a specific GSDME inhibitor, rescued EV-A71-induced T-cell loss, and significantly improved the survival rate (80%) of EV-A71-infected newborn mice. Furthermore, the combined treatment with MeCbl and AGS-A (a T cell-dependent therapeutic agent) exerted a synergistic protective effect, achieving 90% survival rate in wild-type mice, which was abrogated in T cell-deficient BALB/c-nu^−/− mice. Collectively, our findings identify GSDME-dependent T-cell pyroptosis as a key pathogenic mechanism of EV-A71 infection and highlight MeCbl as a promising targeted agent for HFMD treatment, either used alone or in combination with AGS-A.</div></div>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"41 3","pages":"Pages 651-661"},"PeriodicalIF":4.7,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148101893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A ferritin nanoparticle-displayed spike protein-based ELISA for serological surveillance and immune evaluation of porcine deltacoronavirus","authors":"Rui Geng,&nbsp;Hanqin Shen,&nbsp;Duan Li,&nbsp;Shengjin Liu,&nbsp;Siying Zeng,&nbsp;Feng Chen,&nbsp;Hao Zhang,&nbsp;Yongchang Cao","doi":"10.1016/j.virs.2026.06.009","DOIUrl":"10.1016/j.virs.2026.06.009","url":null,"abstract":"","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"41 3","pages":"Pages 720-723"},"PeriodicalIF":4.7,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148253578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bruton's tyrosine kinase inhibitor BTKi-2 inhibits mpox virus and vaccinia virus infection","authors":"Chen Yang,&nbsp;Runchu Zhao,&nbsp;Shuting Huo,&nbsp;Yaqing Zhang,&nbsp;Jingxi Feng,&nbsp;Mingli Gong,&nbsp;Lin Zhu,&nbsp;Conggang Zhang,&nbsp;Linqi Zhang,&nbsp;Jing Xue,&nbsp;Rong Zhang,&nbsp;Qihui Wang,&nbsp;Qiang Ding","doi":"10.1016/j.virs.2026.06.011","DOIUrl":"10.1016/j.virs.2026.06.011","url":null,"abstract":"<div><div>The recent global outbreak of mpox virus (MPXV) infections underscores the urgent need for antiviral therapies against orthopoxviruses. In this study, using a high-content screening (HCS) platform based on a modified vaccinia virus Tiantan strain with GFP insertion (MVTT-GFP) under BSL-2 conditions, we screened 1513 kinase inhibitors for antiviral activity. Among these, Bruton's tyrosine kinase inhibitor BTKi-2 emerged as a potent candidate, exhibiting IC₅₀ of 0.535 μM against vaccinia virus (VACV) and 0.260 μM against MPXV <em>in vitro</em>, while maintaining low cytotoxicity. In a murine model of VACV-induced pneumonia, BTKi-2 treatment reduced lung viral loads by 90% and a significantly improved survival compared to vehicle-treated controls. Notably, mechanistic studies indicate that BTKi-2's antiviral effects cannot be completely attributed to the inhibition of BTK or EGFR/ErbB2 signaling. These findings highlight BTKi-2 as a promising antiviral agent <em>in vitro</em> and <em>in vivo</em>, suggesting that BTKi-2 may offer a potential avenue for future therapeutic development against orthopoxvirus infections.</div></div>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"41 3","pages":"Pages 700-710"},"PeriodicalIF":4.7,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148284474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nanobody targeting glycan cap confers broad orthoebolavirus neutralization","authors":"Xinhui Zhang ,&nbsp;Yi Liao ,&nbsp;Xiuying Liu ,&nbsp;Jingya Zhou ,&nbsp;Peixiang Gao ,&nbsp;Xuemeng Dong ,&nbsp;Shengnan Pan ,&nbsp;Huarui Duan ,&nbsp;Junyu Liu ,&nbsp;Xiaojing Chi ,&nbsp;Wei Yang","doi":"10.1016/j.virs.2026.03.018","DOIUrl":"10.1016/j.virs.2026.03.018","url":null,"abstract":"<div><div>The Zaire Ebola virus (EBOV) and Bundibugyo virus (BDBV) cause severe hemorrhagic fever with high mortality, highlighting the urgent need for broad-spectrum antiviral therapies. Neutralizing nanobodies, with their small size, structural stability, and ability to access sterically restricted epitopes, represent a promising antiviral modality. Here, we identified a high-affinity nanobody, BDBV-Nb02, from a fully synthetic phage display library targeting the glycan cap of BDBV glycoprotein (GP1). BDBV-Nb02 demonstrated strong binding kinetics (KD ≈ 1 nM) and potent neutralizing activity against both BDBV and EBOV pseudoviruses, with half-maximal inhibitory concentration (IC₅₀) values in the nanomolar range. Engineering a bivalent format significantly enhanced neutralization potency, achieving up to a 56-fold reduction in the 90% inhibitory concentration (IC₉₀) compared with the monovalent form. Epitope competition assays and molecular docking revealed that BDBV-Nb02 targets a conserved glycan cleft, with residues F248 and NP278/279 identified as critical neutralization sites. In contrast, Fc-fusion constructs impaired the nanobody's efficacy, highlighting the importance of preserving the structural features that enable access to glycan-shielded epitopes. Our findings demonstrate that BDBV-Nb02 is a promising candidate for broad-spectrum orthoebolavirus therapy and may serve as a valuable component in future antiviral cocktail formulations.</div></div>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"41 2","pages":"Pages 413-422"},"PeriodicalIF":4.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147655170","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unveiling the cryptic diversity and distribution of elements related to virophage mavirus through deep mining of pPolB proteins","authors":"Yutong Wei,&nbsp;Qiyan Liu,&nbsp;Zhen Gong,&nbsp;Guan-Zhu Han","doi":"10.1016/j.virs.2026.03.009","DOIUrl":"10.1016/j.virs.2026.03.009","url":null,"abstract":"<div><div>Virophages are unique double-stranded DNA (dsDNA) viruses that parasitize viruses of <em>Nucleocytoviricota</em> (NCVs). While conventionally viewed as a viral group, growing evidence suggests that “virophage” is better understood as a parasitic lifestyle, rather than a natural group. Despite this conceptual shift, their diversity and evolution remain largely obscure and contentious. Through deep mining of protein-primed type B DNA polymerase (pPolB) in 7041 eukaryotic genomes and 12,053 metagenomes sampled globally, we expand the diversity of pPolB-carrying mavirus virophage-related elements (pMVREs), which include virophages, transpovirons, and Polinton-like viruses (PLVs). Our phylogenomic and metagenomic mining reveals the widespread distribution of pMVREs in eukaryotic genomes (97/7041, 1.38%) and global environments (2450/12053, 20.33%). pMVREs possess genome architectures of high plasticity and promiscuity. The presence of pMVREs and NCVs is statistically correlated in both eukaryotic genomes and global metagenomes, supporting a specific co-occurrence association between pMVREs and NCVs. Moreover, pMVRE diversity and composition exhibit strong heterogeneity across global ecosystems. Together, this study unveils a vast diversity of virophage-related elements and provides insights into the intricate relationship among virophages, transpovirons, PLVs, pMVREs, and NCVs.</div></div>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"41 2","pages":"Pages 371-381"},"PeriodicalIF":4.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147522292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A natural five-amino-acid insert at the S2’ cleavage site of MERS-CoV spike enhances viral membrane fusion","authors":"Guimin Dai,&nbsp;Wenjie Chen,&nbsp;Wenying Cao,&nbsp;Guigen Zhang","doi":"10.1016/j.virs.2026.04.006","DOIUrl":"10.1016/j.virs.2026.04.006","url":null,"abstract":"","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"41 2","pages":"Pages 485-489"},"PeriodicalIF":4.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147718325","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification and characterization of a novel ulcerative enteritis-associated adenovirus of quail causing cross-species infection in chickens","authors":"Hui Tang ,&nbsp;Yin Shi ,&nbsp;Qing Zhang,&nbsp;Fei Zhu,&nbsp;Jia-Yao Hou,&nbsp;Jing-Ying Liao,&nbsp;Yi-Shuai Zhang,&nbsp;Chang-Xin Jing,&nbsp;Xin-Qi Liu,&nbsp;Chao-Ting Xiao","doi":"10.1016/j.virs.2026.04.002","DOIUrl":"10.1016/j.virs.2026.04.002","url":null,"abstract":"","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"41 2","pages":"Pages 474-477"},"PeriodicalIF":4.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147677160","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metatranscriptomics uncovers host immune and microbiome signatures specific to and shared between human metapneumovirus and respiratory syncytial virus infections in children","authors":"Hongwei Zhao ,&nbsp;Ju Yin ,&nbsp;Yingdong Dong ,&nbsp;Qianyu Feng ,&nbsp;Huifang Liu ,&nbsp;Shuaibing Han ,&nbsp;Zhengde Xie ,&nbsp;Lili Xu","doi":"10.1016/j.virs.2026.03.002","DOIUrl":"10.1016/j.virs.2026.03.002","url":null,"abstract":"<div><div>Human metapneumovirus (hMPV) is a prevalent respiratory virus in children with acute lower respiratory tract infections that is highly homologous with respiratory syncytial virus (RSV), the primary etiological agent of pediatric upper and lower respiratory tract infections. Although hMPV and RSV are the only human pathogens within the <em>Pneumoviridae</em> family and share similar clinical manifestations, the mechanisms underlying their divergent pathogenicity remain poorly understood. In this study, we performed transcriptomic analysis on clinical respiratory samples collected between 2017 and 2019 from 61 children: including hMPV-infected, RSV-infected and healthy controls. This analysis revealed a shared upregulation of antiviral response pathways, including neutrophil activation and signaling mediated by interferons and interleukins. Conversely, cilium organization and assembly pathways were commonly downregulated in both infections. hMPV infection uniquely upregulated pathways associated with extracellular component activity, ion channel complexes, and neuroactive ligand‒receptor interactions. In contrast, pathways related to membrane rafts and membrane microdomains were uniquely downregulated in hMPV-infected patients. Analysis of differentially expressed immune-related and interferon-stimulated genes revealed significant hMPV-specific increases in <em>EGF</em> and <em>FCGR1A</em>, alongside decreased <em>EPAS1</em> expression. The genes that were uniquely upregulated during hMPV infection were enriched in cytokine production regulation, cytokine-cytokine receptor interactions, and PI3K/AKT signaling, whereas those that were uniquely downregulated involved the viral entry and endocytic vesicle pathways. Both hMPV infection and RSV infection significantly increased the proportions of M1 macrophages and neutrophils but decreased the proportions of M0 and M2 macrophages. Notably, hMPV infection resulted in a significant increase in monocytes and activated NK cells coupled with a decrease in resting memory CD4⁺ T cells, compared with RSV infection. The results also revealed a significantly greater relative abundance of <em>Prevotella salivae</em> in the hMPV infection group, whereas <em>Streptococcus salivarius</em> and <em>Streptococcus mitis</em> were enriched in the RSV group. These distinct immune and microbial signatures provide novel insights into the pathogenesis of pediatric hMPV and RSV infections.</div></div>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"41 2","pages":"Pages 276-292"},"PeriodicalIF":4.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147459878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}