Autophagy induced by human adenovirus B7 structural protein VI inhibits viral replication

Linlin Zhang; Yali Duan; Wei Wang; Qi Li; Jiao Tian; Yun Zhu; Ran Wang; Zhengde Xie

doi:10.1016/j.virs.2023.08.002

October 2023

Linlin Zhang, Yali Duan, Wei Wang, Qi Li, Jiao Tian, Yun Zhu, Ran Wang and Zhengde Xie. Autophagy induced by human adenovirus B7 structural protein VI inhibits viral replication[J]. Virologica Sinica, 2023, 38(5): 709-722. doi: 10.1016/j.virs.2023.08.002

Citation: Linlin Zhang, Yali Duan, Wei Wang, Qi Li, Jiao Tian, Yun Zhu, Ran Wang, Zhengde Xie. Autophagy induced by human adenovirus B7 structural protein VI inhibits viral replication .VIROLOGICA SINICA, 2023, 38(5) : 709-722. http://dx.doi.org/10.1016/j.virs.2023.08.002

人腺病毒B组7型的结构蛋白VI诱导的自噬可抑制病毒复制

张林琳 ^a,b ,
段亚丽 ^a,b,c ,
王巍 ^a,b,d ,
李奇 ^a,b ,
田娇 ^a,b ,
朱云 ^a,b ,
王然 ^a,b ,
谢正德 ^a,b,,

国家儿童医学中心国家呼吸系统临床医学研究中心首都医科大学附属北京儿童医院儿科重大疾病研究教育部重点实验室中国医学科学院儿童危重感染诊治创新单元儿童呼吸道感染性疾病研究北京市重点实验室北京市儿科研究所感染与病毒研究室; 国家儿童医学中心首都医科大学附属北京儿童医院感染与病毒研究室

通讯作者： 谢正德, xiezhengde@bch.com.cn
收稿日期： 2023-02-09
录用日期： 2023-07-31

摘要

人腺病毒B组7型（Human adenovirus B7，HAdV-B7）是引起儿童急性下呼吸道感染的重要病毒病原，严重威胁儿童生命健康。然而，其致病机制尚不明确，目前我国尚无安全有效的儿童腺病毒疫苗以及特异性抗HAdV-B7药物。细胞自噬作为维持细胞内环境稳态以及宿主抗病毒免疫的重要组成部分，不仅可以通过病毒吞噬直接将病毒转运到自噬溶酶体中降解，还可以协助宿主细胞激活固有和适应性免疫，发挥抵抗病毒感染的作用。本研究中发现HAdV-B7感染可诱导完整的自噬通量，应用自噬诱导剂雷帕霉素上调自噬可抑制HAdV-B7的复制。此外，本研究还发现宿主自噬受体蛋白Bcl-2关联永生基因3（Bcl-2 associated athanogene 3，BAG3）通过其WW结构域与病毒蛋白pVI的PPSY结构域结合，介导自噬抑制HAdV-B7的复制。这些研究结果为探索HAdV-B7感染与宿主细胞相互作用的分子机制提供了参考数据。通过自噬调节剂调节宿主细胞中BAG3介导的自噬通路或可为治疗HAdV-B7感染提供新的思路。
- 人腺病毒B组7型
- , 自噬
- , Bcl-2关联永生基因3
- , 病毒复制

Autophagy induced by human adenovirus B7 structural protein VI inhibits viral replication

Linlin Zhang ^a,b ,
Yali Duan ^a,b,c ,
Wei Wang ^a,b,d ,
Qi Li ^a,b ,
Jiao Tian ^a,b ,
Yun Zhu ^a,b ,
Ran Wang ^a,b ,
Zhengde Xie ^a,b,,

a. Beijing Key Laboratory of Pediatric Respiratory Infectious Diseases, Key Laboratory of Major Diseases in Children, Ministry of Education, National Clinical Research Center for Respiratory Diseases, Laboratory of Infection and Virology, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, 100045, China;
b. Research Unit of Critical Infection in Children, 2019RU016, Chinese Academy of Medical Sciences, Beijing, 100045, China;
c. Department of Infectious Diseases, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, 100045, China;
d. Beijing Coal Group General Hospital, Beijing, 100045, China

Corresponding author: Zhengde Xie, xiezhengde@bch.com.cn
Received Date: 09 February 2023
Accepted Date: 31 July 2023

Abstract

Human adenovirus B7 (HAdV-B7) causes severe acute lower respiratory tract infections in children. However, neither the child-specific antivirals or vaccines are available, nor the pathogenesis is clear. Autophagy, as part of innate immunity, plays an important role in resistance to viral infection by degrading the virus and promoting the development of innate and adaptive immunity. This study provided evidence that HAdV-B7 infection induced complete autophagic flux, and the pharmacological induction of autophagy decreased HAdV-B7 replication. In this process, the host protein Bcl2-associated athanogene 3 (BAG3) mediated autophagy to inhibit the replication of HAdV-B7 by binding to the PPSY structural domain of viral protein pVI through its WW structural domain. These findings further our understanding of the host immune response during viral infection and will help to develop broad anti-HAdV therapies.
- Human adenovirus B7 (HAdV-B7)
- , Autophagy
- , Bcl2-associated athanogene 3 (BAG3)
- , Virus replication

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