Pub Date : 2025-10-01DOI: 10.1016/j.virs.2025.10.001
Lu He , Xuxu Fan , Zhaoyu Zhu , Danshi Pei , Yizhuo Wang , Xizhong Li , Qingfeng Ren , Haixue Zheng , Weiwei Li , Zixiang Zhu
African swine fever (ASF) is an acute, hemorrhagic, and highly contagious disease in pigs caused by the African swine fever virus (ASFV). Our previous studies have demonstrated that deletion of the MGF360-9L gene weakens ASFV virulence in pigs, yet the underlying mechanism remains unclear. To investigate the mechanism of MGF360-9L regulating ASFV pathogenicity, the relationship between MGF360-9L and host proteins was identified by mass spectrometry. We found that host protein DEAD-box helicase 20 (DDX20) interacted with and colocalized with MGF360-9L. Overexpression of DDX20 inhibited ASFV replication, whereas knockdown of DDX20 had the opposite effects. Moreover, DDX20 inhibited ASFV replication by promoting the activation of type I interferon signaling. Surprisingly, DDX20 was gradually degraded following ASFV infection. Mechanistically, MGF360-9L promoted the autophagic degradation of DDX20 by recruiting autophagy-related protein Ras-related protein Rab-1A (Rab1A). Silencing Rab1A suppressed ASFV replication, while overexpression of Rab1A exhibited the opposite effects. Furthermore, Rab1A, MGF360-9L and DDX20 could form a complex to facilitate the degradation of DDX20. Knockdown of Rab1A impaired MGF360-9L-mediated degradation of DDX20 during ASFV infection. In summary, our study demonstrates that MGF360-9L targets DDX20 for autophagy degradation to antagonize its antiviral function and facilitate ASFV replication. This finding broadens our understanding of the regulatory network between ASFV and its host, and provides new insights into the pathogenesis and immune evasion mechanisms of ASFV.
{"title":"African swine fever virus MGF360-9L degrades DDX20 through the Rab1A-dependent autophagy pathway to antagonize its antiviral effect","authors":"Lu He , Xuxu Fan , Zhaoyu Zhu , Danshi Pei , Yizhuo Wang , Xizhong Li , Qingfeng Ren , Haixue Zheng , Weiwei Li , Zixiang Zhu","doi":"10.1016/j.virs.2025.10.001","DOIUrl":"10.1016/j.virs.2025.10.001","url":null,"abstract":"<div><div>African swine fever (ASF) is an acute, hemorrhagic, and highly contagious disease in pigs caused by the African swine fever virus (ASFV). Our previous studies have demonstrated that deletion of the <em>MGF360-9L</em> gene weakens ASFV virulence in pigs, yet the underlying mechanism remains unclear. To investigate the mechanism of MGF360-9L regulating ASFV pathogenicity, the relationship between MGF360-9L and host proteins was identified by mass spectrometry. We found that host protein DEAD-box helicase 20 (DDX20) interacted with and colocalized with MGF360-9L. Overexpression of DDX20 inhibited ASFV replication, whereas knockdown of DDX20 had the opposite effects. Moreover, DDX20 inhibited ASFV replication by promoting the activation of type I interferon signaling. Surprisingly, DDX20 was gradually degraded following ASFV infection. Mechanistically, MGF360-9L promoted the autophagic degradation of DDX20 by recruiting autophagy-related protein Ras-related protein Rab-1A (Rab1A). Silencing Rab1A suppressed ASFV replication, while overexpression of Rab1A exhibited the opposite effects. Furthermore, Rab1A, MGF360-9L and DDX20 could form a complex to facilitate the degradation of DDX20. Knockdown of Rab1A impaired MGF360-9L-mediated degradation of DDX20 during ASFV infection. In summary, our study demonstrates that MGF360-9L targets DDX20 for autophagy degradation to antagonize its antiviral function and facilitate ASFV replication. This finding broadens our understanding of the regulatory network between ASFV and its host, and provides new insights into the pathogenesis and immune evasion mechanisms of ASFV.</div></div>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"40 5","pages":"Pages 822-834"},"PeriodicalIF":4.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145309279","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}
Pub Date : 2025-10-01DOI: 10.1016/j.virs.2025.07.008
Yuting Xu , Shihai Wu , Lei Ji , Jie Hu , Jin Wang , Ke Li , Yue Yuan , Gaojian Li , Guangjian Zhu , Panyu Hua , Qiuhong Miao , Hongxuan He , Guimei He
{"title":"Black swans as sentinel species for the emergence of clade 2.3.4.4b highly pathogenic avian influenza (H5N1) in Shanghai, China, 2024","authors":"Yuting Xu , Shihai Wu , Lei Ji , Jie Hu , Jin Wang , Ke Li , Yue Yuan , Gaojian Li , Guangjian Zhu , Panyu Hua , Qiuhong Miao , Hongxuan He , Guimei He","doi":"10.1016/j.virs.2025.07.008","DOIUrl":"10.1016/j.virs.2025.07.008","url":null,"abstract":"","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"40 5","pages":"Pages 853-855"},"PeriodicalIF":4.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144683244","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}
Pub Date : 2025-10-01DOI: 10.1016/j.virs.2025.09.002
Jinjin Wang , Ling Jing , Yali Duan , Junhong Ai , Yun Zhu , Ran Wang , Xiangpeng Chen , Gen Lu , Yun Sun , Changchong Li , Rong Jin , Yunxiao Shang , Yixiao Bao , Shuhua An , Yunlian Zhou , Limin Ning , Baoping Xu , Yuhai Bi , Zhengde Xie
Human adenovirus type 108 (HAdV-108) has been detected in multiple countries, including China, and is associated with severe acute respiratory infection (ARI) in children, with reported fatalities. However, studies on HAdV-108 remain limited. This study aimed to investigate the clinical and genetic characteristics of HAdV-108 in ARI children in China. From 2014 to 2024, 6720 respiratory samples were collected from hospitalized children with ARI at ten hospitals across northern and southern China, of which 505 (7.51%) tested positive for HAdV. The whole-genome and three major capsid protein genes were amplified and sequenced for bioinformatics analysis, which revealed that among 317 HAdV-isolated samples, 21 (6.62%) were identified as HAdV-108, ranking third after HAdV-114 and HAdV-7. Clinical analysis of HAdV-108-positive cases showed that the main manifestations were cough and fever. Seven children had gastrointestinal symptoms, and two children without underlying diseases were diagnosed with severe pneumonia. Phylogenetic analysis of whole-genome sequences revealed distinct predominant epidemic branches between domestic and international strains, with one strain obtained in this study forming an independent branch. Hexon protein exhibited the fastest evolution rate, lowest identity, and greatest amino acid variability, while fiber protein displayed the slowest evolution rate, highest identity, and greatest conservation and stability. Compared with the earliest reported HAdV-108 strain, three amino acid deletions were identified in the RGD loop region of penton base protein, resulting in potential structural change. Recombination analysis identified five distinct recombination patterns. In vitro experiments demonstrated that HAdV-108 had proliferation capacity comparable to other species C adenoviruses. In summary, HAdV-108 has persistently circulated in China, causing severe ARIs and concurrent gastrointestinal manifestations. Cluster3 was the predominant epidemic branch in China. HAdV-108 exhibited significant intra-type genetic variation, with random and diverse recombination events.
{"title":"Genetic analysis of human adenovirus type 108 circulating in China during 2014–2024","authors":"Jinjin Wang , Ling Jing , Yali Duan , Junhong Ai , Yun Zhu , Ran Wang , Xiangpeng Chen , Gen Lu , Yun Sun , Changchong Li , Rong Jin , Yunxiao Shang , Yixiao Bao , Shuhua An , Yunlian Zhou , Limin Ning , Baoping Xu , Yuhai Bi , Zhengde Xie","doi":"10.1016/j.virs.2025.09.002","DOIUrl":"10.1016/j.virs.2025.09.002","url":null,"abstract":"<div><div>Human adenovirus type 108 (HAdV-108) has been detected in multiple countries, including China, and is associated with severe acute respiratory infection (ARI) in children, with reported fatalities. However, studies on HAdV-108 remain limited. This study aimed to investigate the clinical and genetic characteristics of HAdV-108 in ARI children in China. From 2014 to 2024, 6720 respiratory samples were collected from hospitalized children with ARI at ten hospitals across northern and southern China, of which 505 (7.51%) tested positive for HAdV. The whole-genome and three major capsid protein genes were amplified and sequenced for bioinformatics analysis, which revealed that among 317 HAdV-isolated samples, 21 (6.62%) were identified as HAdV-108, ranking third after HAdV-114 and HAdV-7. Clinical analysis of HAdV-108-positive cases showed that the main manifestations were cough and fever. Seven children had gastrointestinal symptoms, and two children without underlying diseases were diagnosed with severe pneumonia. Phylogenetic analysis of whole-genome sequences revealed distinct predominant epidemic branches between domestic and international strains, with one strain obtained in this study forming an independent branch. Hexon protein exhibited the fastest evolution rate, lowest identity, and greatest amino acid variability, while fiber protein displayed the slowest evolution rate, highest identity, and greatest conservation and stability. Compared with the earliest reported HAdV-108 strain, three amino acid deletions were identified in the RGD loop region of penton base protein, resulting in potential structural change. Recombination analysis identified five distinct recombination patterns. <em>In vitro</em> experiments demonstrated that HAdV-108 had proliferation capacity comparable to other species C adenoviruses. In summary, HAdV-108 has persistently circulated in China, causing severe ARIs and concurrent gastrointestinal manifestations. Cluster3 was the predominant epidemic branch in China. HAdV-108 exhibited significant intra-type genetic variation, with random and diverse recombination events.</div></div>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"40 5","pages":"Pages 694-709"},"PeriodicalIF":4.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145114236","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}
Pub Date : 2025-10-01DOI: 10.1016/j.virs.2025.10.005
Chunzheng Li , Hongyue Li , Yuanchi Ye , Lianglong Zhu , Aihua Zheng , Xing Zhang
Severe fever with thrombocytopenia syndrome virus (SFTSV), an emerging tick-borne pathogen, has caused a rising number of human cases in the urban-rural fringe of Beijing since 2021. This study explores the seasonal dynamics of hedgehog-associated ticks and SFTSV transmission in urban parks of Beijing. Surveys across six parks revealed distinct activity patterns: adult Haemaphysalis longicornis peaked in summer, while nymphs dominated spring and autumn. All collected H. longicornis belonged to parthenogenetic populations. A near-complete SFTSV genome (C4 strain) was identified in a tick collected from Taoranting Park, suggesting multiple viral introductions into Beijing. Serological analysis showed that > 50% of hedgehogs carried SFTSV-neutralizing antibodies in spring; yet seropositivity declined markedly in summer and autumn, indicating recurrent infections and implicating hedgehogs as potential reservoirs. These findings reveal an urban SFTSV transmission cycle maintained by hedgehogs and parthenogenetic H. longicornis, emphasizing the urgency of enhanced surveillance and public health interventions to curb urban zoonotic risks.
{"title":"Seasonal dynamics of hedgehog-borne ticks and severe fever with thrombocytopenia syndrome virus in Beijing's urban parks","authors":"Chunzheng Li , Hongyue Li , Yuanchi Ye , Lianglong Zhu , Aihua Zheng , Xing Zhang","doi":"10.1016/j.virs.2025.10.005","DOIUrl":"10.1016/j.virs.2025.10.005","url":null,"abstract":"<div><div>Severe fever with thrombocytopenia syndrome virus (SFTSV), an emerging tick-borne pathogen, has caused a rising number of human cases in the urban-rural fringe of Beijing since 2021. This study explores the seasonal dynamics of hedgehog-associated ticks and SFTSV transmission in urban parks of Beijing. Surveys across six parks revealed distinct activity patterns: adult <em>Haemaphysalis longicornis</em> peaked in summer, while nymphs dominated spring and autumn. All collected <em>H. longicornis</em> belonged to parthenogenetic populations. A near-complete SFTSV genome (C4 strain) was identified in a tick collected from Taoranting Park, suggesting multiple viral introductions into Beijing. Serological analysis showed that > 50% of hedgehogs carried SFTSV-neutralizing antibodies in spring; yet seropositivity declined markedly in summer and autumn, indicating recurrent infections and implicating hedgehogs as potential reservoirs. These findings reveal an urban SFTSV transmission cycle maintained by hedgehogs and parthenogenetic <em>H. longicornis</em>, emphasizing the urgency of enhanced surveillance and public health interventions to curb urban zoonotic risks.</div></div>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"40 5","pages":"Pages 748-754"},"PeriodicalIF":4.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145337538","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}
Tick-borne encephalitis virus (TBEV) is a re-emerging pathogen in Kazakhstan, where the increasing risk of its spread underscores the need for improved healthcare preparedness, including the development of local vaccines. However, the absence of reference TBEV strains in the country presented a major challenge. To address this, we generated a prototype strain (Vasilchenko) of the Siberian TBEV genotype, predominant in Kazakhstan, using synthetic genome and molecular infectious clone technology. A DNA-launched TBEV molecular clone was assembled from DNA fragments, enabling virus rescue upon plasmid transfection. During the propagation of the post-transfection virus in cell culture, a single amino acid substitution (E51K) in the envelope protein emerged, resulting in a 100-fold increase in the titer of the mutant variant. In vivo, this mutation significantly attenuated virulence: while wild-type TBEV caused 100% mortality in BALB/c mice, the E51K variant was non-lethal and exhibited reduced viremia, suggesting impaired neuroinvasiveness. To further exploit this attenuated, high-titer virus, we developed a GFP-expressing reporter TBEV variant. Using this reporter system, we demonstrated that favipiravir possesses antiviral activity against TBEV, with inhibitory concentrations within a pharmacologically relevant range. In conclusion, synthetic genomics enabled the generation of a reference TBEV strain to replenish Kazakhstan's collections. The E51K mutation enhances viral replication in vitro while attenuating pathogenicity in vivo, and the derived reporter virus is suitable for antiviral compound screening.
{"title":"Synthetic genomics-based generation of the tick-borne encephalitis virus Siberian subtype prototype strain and E51K-attenuated variant for vaccine development and antiviral screening","authors":"Tolganay Kulatay , Elena Sedova , Alexander Shevtsov , Gulzat Zauatbayeva , Bakytkali Ingirbay , Viktoriya Keyer , Zhanar Shakhmanova , Maral Zhumabekova , Yergali Abduraimov , Aralbek Rsaliyev , Nurgul Sikhayeva , Irina Kozlova , Mikhail Zaripov , Alexandr V. Shustov","doi":"10.1016/j.virs.2025.09.010","DOIUrl":"10.1016/j.virs.2025.09.010","url":null,"abstract":"<div><div>Tick-borne encephalitis virus (TBEV) is a re-emerging pathogen in Kazakhstan, where the increasing risk of its spread underscores the need for improved healthcare preparedness, including the development of local vaccines. However, the absence of reference TBEV strains in the country presented a major challenge. To address this, we generated a prototype strain (Vasilchenko) of the Siberian TBEV genotype, predominant in Kazakhstan, using synthetic genome and molecular infectious clone technology. A DNA-launched TBEV molecular clone was assembled from DNA fragments, enabling virus rescue upon plasmid transfection. During the propagation of the post-transfection virus in cell culture, a single amino acid substitution (E51K) in the envelope protein emerged, resulting in a 100-fold increase in the titer of the mutant variant. <em>In vivo</em>, this mutation significantly attenuated virulence: while wild-type TBEV caused 100% mortality in BALB/c mice, the E51K variant was non-lethal and exhibited reduced viremia, suggesting impaired neuroinvasiveness. To further exploit this attenuated, high-titer virus, we developed a GFP-expressing reporter TBEV variant. Using this reporter system, we demonstrated that favipiravir possesses antiviral activity against TBEV, with inhibitory concentrations within a pharmacologically relevant range. In conclusion, synthetic genomics enabled the generation of a reference TBEV strain to replenish Kazakhstan's collections. The E51K mutation enhances viral replication <em>in vitro</em> while attenuating pathogenicity <em>in vivo</em>, and the derived reporter virus is suitable for antiviral compound screening.</div></div>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"40 5","pages":"Pages 812-821"},"PeriodicalIF":4.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145228300","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}
Pub Date : 2025-10-01DOI: 10.1016/j.virs.2025.08.004
Chuntian Li , Yuncheng Li , Ranqing Cheng , Miaomiao Li , Mudan Zhang , Zhiyuan Zhu , Ping Yang , Qinxue Hu , Yalan Liu
Herpes simplex virus 2 (HSV-2) is a major pathogen causing neonatal herpes and increasing the risk of human immunodeficiency virus 1 (HIV-1) infection. However, the mechanisms underlying host restriction of HSV-2 infection are still not fully understood. The ubiquitously expressed transcript isoform 2 (UXT-V2), an α-type prefoldin protein, functions as a versatile transcription factor associated with numerous human tumors, but its role in viral infection remains unclear. In this study, we found that ectopic expression of UXT-V2 significantly inhibited HSV-2 replication, while knockout of endogenously expressed UXT-V2 promoted HSV-2 proliferation. Further analysis revealed that UXT-V2 restricts HSV-2 replication independent of its role in regulating NF-κB. In the context of HSV-2 infection or in viral glycoprotein B (gB)-transfected cells, UXT-V2 facilitates K48-linked ubiquitination of gB, leading to its degradation via the proteasome pathway, thereby inhibiting viral replication. Furthermore, we identified that UXT-V2 interacts with gB, recruiting the E3 ligase TRIM21 to facilitate K48-linked ubiquitination of gB. HSV-2, in turn, reduces the abundance of UXT-V2 proteins both in vitro and in mice, highlighting the complexity of HSV-2-host interactions. Collectively, our findings, for the first time, demonstrate an anti-HSV-2 role of UXT-V2, unveiling a novel host immune defense mechanism involved in regulating glycoprotein homeostasis.
{"title":"Ubiquitously expressed transcript isoform 2 (UXT-V2) restricts HSV-2 replication by targeting glycoprotein B for degradation through ubiquitin-proteasome pathway","authors":"Chuntian Li , Yuncheng Li , Ranqing Cheng , Miaomiao Li , Mudan Zhang , Zhiyuan Zhu , Ping Yang , Qinxue Hu , Yalan Liu","doi":"10.1016/j.virs.2025.08.004","DOIUrl":"10.1016/j.virs.2025.08.004","url":null,"abstract":"<div><div>Herpes simplex virus 2 (HSV-2) is a major pathogen causing neonatal herpes and increasing the risk of human immunodeficiency virus 1 (HIV-1) infection. However, the mechanisms underlying host restriction of HSV-2 infection are still not fully understood. The ubiquitously expressed transcript isoform 2 (UXT-V2), an α-type prefoldin protein, functions as a versatile transcription factor associated with numerous human tumors, but its role in viral infection remains unclear. In this study, we found that ectopic expression of UXT-V2 significantly inhibited HSV-2 replication, while knockout of endogenously expressed UXT-V2 promoted HSV-2 proliferation. Further analysis revealed that UXT-V2 restricts HSV-2 replication independent of its role in regulating NF-κB. In the context of HSV-2 infection or in viral glycoprotein B (gB)-transfected cells, UXT-V2 facilitates K48-linked ubiquitination of gB, leading to its degradation via the proteasome pathway, thereby inhibiting viral replication. Furthermore, we identified that UXT-V2 interacts with gB, recruiting the E3 ligase TRIM21 to facilitate K48-linked ubiquitination of gB. HSV-2, in turn, reduces the abundance of UXT-V2 proteins both <em>in vitro</em> and in mice, highlighting the complexity of HSV-2-host interactions. Collectively, our findings, for the first time, demonstrate an anti-HSV-2 role of UXT-V2, unveiling a novel host immune defense mechanism involved in regulating glycoprotein homeostasis.</div></div>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"40 5","pages":"Pages 778-792"},"PeriodicalIF":4.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145001170","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}
Pub Date : 2025-10-01DOI: 10.1016/j.virs.2025.07.005
Haobin Li , Huiyi Guo , Binhao Rong , Haowei Li , Wenjiao Wu , Chan Yang , Shuwen Liu
The ongoing coronavirus epidemic, including the novel coronavirus (SARS-CoV-2), continues to pose a significant threat to global public health. Host targets address multiple stages of the viral life cycle and provide diverse opportunities for therapeutic interventions. This study identified sorting nexin 10 (SNX10) as a facilitator of replication of human coronavirus OC43 (HCoV-OC43), underscoring its potential as a novel antiviral target. The knockout of SNX10 significantly suppressed HCoV-OC43 replication both in vivo and in vitro. Immunoprecipitation-mass spectrometry (IP-MS) analysis identified the adaptor protein complex 2 subunit μ1 (AP2M1) as a direct interactor of SNX10. Specifically, SNX10 facilitates phosphorylation of the AP2M1, thereby enhancing clathrin-mediated viral endocytosis. Furthermore, subsequent binding and internalization assays revealed that SNX10 knockout significantly inhibits viral entry into host cells. Conversely, the reconstitution of SNX10 fully restored viral entry, thereby confirming the critical and indispensable role of SNX10 in pathogen internalization. Simultaneously, SNX10 was identified as a key factor that promotes endosomal acidification by modulating pH levels, which in turn facilitated the release of the viral genome. Notably, the ablation of SNX10 was found to trigger autophagy activation during infection, thereby maintaining intracellular homeostasis. Additionally, it exerted autonomous antiviral effects through lysosomal degradation pathways. Collectively, these findings demonstrate SNX10 serves as a pivotal regulator of the viral life cycle and underscore its therapeutic potential as a multi-faceted antiviral candidate target capable of simultaneously inhibiting viral internalization, viral genomic release, and host-pathogen equilibrium.
{"title":"SNX10 enhances HCoV-OC43 infection by facilitating viral entry and inhibiting virus-triggered autophagy","authors":"Haobin Li , Huiyi Guo , Binhao Rong , Haowei Li , Wenjiao Wu , Chan Yang , Shuwen Liu","doi":"10.1016/j.virs.2025.07.005","DOIUrl":"10.1016/j.virs.2025.07.005","url":null,"abstract":"<div><div>The ongoing coronavirus epidemic, including the novel coronavirus (SARS-CoV-2), continues to pose a significant threat to global public health. Host targets address multiple stages of the viral life cycle and provide diverse opportunities for therapeutic interventions. This study identified sorting nexin 10 (SNX10) as a facilitator of replication of human coronavirus OC43 (HCoV-OC43), underscoring its potential as a novel antiviral target. The knockout of <em>SNX10</em> significantly suppressed HCoV-OC43 replication both <em>in vivo</em> and <em>in vitro</em>. Immunoprecipitation-mass spectrometry (IP-MS) analysis identified the adaptor protein complex 2 subunit μ1 (AP2M1) as a direct interactor of SNX10. Specifically, SNX10 facilitates phosphorylation of the AP2M1, thereby enhancing clathrin-mediated viral endocytosis. Furthermore, subsequent binding and internalization assays revealed that <em>SNX10</em> knockout significantly inhibits viral entry into host cells. Conversely, the reconstitution of SNX10 fully restored viral entry, thereby confirming the critical and indispensable role of SNX10 in pathogen internalization. Simultaneously, SNX10 was identified as a key factor that promotes endosomal acidification by modulating pH levels, which in turn facilitated the release of the viral genome. Notably, the ablation of SNX10 was found to trigger autophagy activation during infection, thereby maintaining intracellular homeostasis. Additionally, it exerted autonomous antiviral effects through lysosomal degradation pathways. Collectively, these findings demonstrate SNX10 serves as a pivotal regulator of the viral life cycle and underscore its therapeutic potential as a multi-faceted antiviral candidate target capable of simultaneously inhibiting viral internalization, viral genomic release, and host-pathogen equilibrium.</div></div>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"40 5","pages":"Pages 755-768"},"PeriodicalIF":4.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144620767","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}
The invasion of host cells by the henipavirus is facilitated through the interaction between viral attachment (G) and fusion (F) glycoproteins with receptors on the cell surface. Langya henipavirus (LayV) was newly identified in China in 2022. The G proteins of LayV and Mojiang virus (MojV) exhibit high amino acid homology (86%), while they are located in a unique evolutionary clade within the Henipavirus genus. In this study, the crystal structure of the LayV G protein was resolved at a 3.37 Å resolution, revealing a head domain with six β-propeller-like domains distinct from other henipavirus G proteins, such as those of Nipah virus (NiV) and Hendra virus (HeV). Furthermore, the prominent loop in the center cavity of the LayV G protein showed unique structural features. In the ELISA and SPR assays, the LayV G protein was unable to bind to the existing henipavirus-neutralizing antibodies or the ephrin-B2 receptor. Immunogenicity studies in mice demonstrated robust antibody responses elicited by the LayV G protein. These antibodies exhibited strong reactivity against both LayV and MojV G proteins. However, only weak cross-reactivity was observed with other henipaviruses. Moreover, eight monoclonal antibodies targeting the LayV G protein were generated, two of which exhibited broad binding activity across different henipavirus G proteins. These findings underscore the need for tailored vaccines and therapeutics for LayV and related novel henipaviruses
{"title":"Antigenic and structural insights into Langya henipavirus attachment glycoprotein","authors":"Yaohui Li , Xiaoyan Huang , Xiaodong Zai, Chenfeng Mao, Ruihua Li, Yamei Feng, Yue Zhang, Zhang Zhang, Jun Zhang, Junjie Xu","doi":"10.1016/j.virs.2025.08.005","DOIUrl":"10.1016/j.virs.2025.08.005","url":null,"abstract":"<div><div>The invasion of host cells by the henipavirus is facilitated through the interaction between viral attachment (G) and fusion (F) glycoproteins with receptors on the cell surface. Langya henipavirus (LayV) was newly identified in China in 2022. The G proteins of LayV and Mojiang virus (MojV) exhibit high amino acid homology (86%), while they are located in a unique evolutionary clade within the <em>Henipavirus</em> genus. In this study, the crystal structure of the LayV G protein was resolved at a 3.37 Å resolution, revealing a head domain with six β-propeller-like domains distinct from other henipavirus G proteins, such as those of Nipah virus (NiV) and Hendra virus (HeV). Furthermore, the prominent loop in the center cavity of the LayV G protein showed unique structural features. In the ELISA and SPR assays, the LayV G protein was unable to bind to the existing henipavirus-neutralizing antibodies or the ephrin-B2 receptor. Immunogenicity studies in mice demonstrated robust antibody responses elicited by the LayV G protein. These antibodies exhibited strong reactivity against both LayV and MojV G proteins. However, only weak cross-reactivity was observed with other henipaviruses. Moreover, eight monoclonal antibodies targeting the LayV G protein were generated, two of which exhibited broad binding activity across different henipavirus G proteins. These findings underscore the need for tailored vaccines and therapeutics for LayV and related novel henipaviruses</div></div>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"40 5","pages":"Pages 769-777"},"PeriodicalIF":4.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145001138","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}
Pub Date : 2025-10-01DOI: 10.1016/j.virs.2025.09.008
YanYing Yan , Zhiqiang Wei , Min Zheng , Mengji Lu , Xueyu Wang
Hepatitis B virus (HBV) establishes chronic infection through strategic manipulation of host metabolic networks, driving a spectrum of hepatic pathologies ranging from hepatitis to cirrhosis and hepatocellular carcinoma. Mechanistically, HBV reprograms core metabolic pathways, including glycolysis, tricarboxylic acid (TCA) cycle, oxidative phosphorylation, and lipid homeostasis, to fuel its replication machinery and evade immune surveillance. This review systematically synthesizes current evidence on HBV-induced glucose/lipid metabolic rewiring, with particular emphasis on how viral-host crosstalk at the metabolic interface sustains viral pathogenesis.
{"title":"HBV and host metabolic crosstalk: Reprogramming pathways for viral replication and pathogenesis","authors":"YanYing Yan , Zhiqiang Wei , Min Zheng , Mengji Lu , Xueyu Wang","doi":"10.1016/j.virs.2025.09.008","DOIUrl":"10.1016/j.virs.2025.09.008","url":null,"abstract":"<div><div>Hepatitis B virus (HBV) establishes chronic infection through strategic manipulation of host metabolic networks, driving a spectrum of hepatic pathologies ranging from hepatitis to cirrhosis and hepatocellular carcinoma. Mechanistically, HBV reprograms core metabolic pathways, including glycolysis, tricarboxylic acid (TCA) cycle, oxidative phosphorylation, and lipid homeostasis, to fuel its replication machinery and evade immune surveillance. This review systematically synthesizes current evidence on HBV-induced glucose/lipid metabolic rewiring, with particular emphasis on how viral-host crosstalk at the metabolic interface sustains viral pathogenesis.</div></div>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"40 5","pages":"Pages 685-693"},"PeriodicalIF":4.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145193133","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}
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