文献类型： 外文期刊

作者： Zhou, Qiongqiong ¹ ; Shi, Deshi ³ ; Tang, Yan-Dong ¹ ; Zhang, Longfeng ¹ ; Liu, Hongyang ¹ ; Ye, Guangqiang ¹ ; Zhang, Zhaoxia ¹ ; Hu, Boli ⁴ ; Huang, Li ¹ ; Weng, Changjiang ¹ ;

作者机构： 1.Chinese Acad Agr Sci, Harbin Vet Res Inst, Div Fundamental Immunol, State Key Lab Anim Dis Prevent & Control, Harbin, Heilongjiang, Peoples R China

2.Chinese Acad Agr Sci, Harbin Vet Res Inst, Heilongjiang Prov Key Lab Vet Immunol, Harbin, Heilongjiang, Peoples R China

3.Huazhong Agr Univ, Coll Vet Med, State Key Lab Agr Microbiol, Wuhan, Hubei, Peoples R China

4.Zhejiang Univ, MOA Key Lab Anim Virol, Ctr Vet Sci, Hangzhou, Zhejiang, Peoples R China

关键词： Caspase 3; gM homologs; inhibit autophagic flux; macroautophagy; protein aggregates; SNAP29

期刊名称：AUTOPHAGY （ 影响因子：14.3； 五年影响因子：17.1 ）

ISSN： 1554-8627

年卷期： 2025 年

页码：

收录情况： SCI

摘要： Macroautophagy/autophagy is a biological process that sequesters and degrades cytoplasmic material, damaged organelles, and infectious pathogens in eukaryotic cells via lysosomes. Autophagy is involved in different phases of the viral life cycle and regulates viral replication. Here, we demonstrated that pseudorabies virus (PRV) infection induced incomplete autophagy, and blocking the autophagosome-lysosome fusion facilitated PRV replication. Mechanistically, PRV late envelope glycoprotein M (gM) triggered SQSTM1/p62-dependent selective autophagy. Meanwhile, gM protein was found to inhibit the fusion between autophagosomes and lysosomes by activating CASP3 (caspase 3) to degrade SNAP29, resulting in increased viral replication. Interestingly, we confirmed that the gM homologs from several herpesviruses (herpes simplex virus-1, human cytomegalovirus, equine herpesvirus-1, and varicella-zoster virus) shared the same function of activating CASP3 and inhibiting autophagic flux. Deletion of the CASP3 gene led to an intact autophagic pathway and the increased formation of autolysosomes. Collectively, our results illustrated that blockage of autophagosome-lysosome fusion mediated by PRV gM and its homologs in other herpesviruses protected viral proteins from host autophagic signaling, thus facilitating herpesvirus replication.Abbreviations: 3-MA: 3-methyladenine; Baf A1: bafilomycin A1; CASP3: caspase 3; cl-CASP3: cleaved-CASP3; co-IP: co-immunoprecipitation; CQ: chloroquine; DAPI: 4',6-diamidino-2-phenylindole; DMSO: dimethyl sulfoxide; EHV-1: equine herpesvirus 1; gM: glycoprotein M; HCMV: human cytomegalovirus; HSV-1: herpes simplex virus 1; LAMP1: lysosomal associated membrane protein 1; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MOI: multiplicity of infection; OD: optical density; PCR: polymerase chain reaction; PFU: plaque forming units; PRV: pseudorabies virus; Rap: rapamycin; SNAP29; synaptosome associated protein 29; SQSTM1/p62: sequestosome 1; STX17: syntaxin 17; TCID: 50% tissue culture infectious doses; UBA: ubiquitin-binding domain; VAMP8: vesicle associated membrane protein 8; mu m, micrometer; VZV: varicella-zoster virus; WT: wild type.