HDAC6, A Novel Cargo for Autophagic Clearance of Stress Granules, Mediates the Repression of the Type I Interferon Response During Coxsackievirus A16 Infection
Autophagic cargoes ensure selective autophagy for the recognition and removal of various cytosolic aggregated proteins, damaged organelles, or pathogens. Stress granules (SGs), as antiviral immune complexes, serve a positive role in the type I interferon (IFN) response and can be targeted by autopha...
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doaj-8582a7bb1c35415b830b9f863fa4cc662020-11-25T01:49:22ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2020-01-011110.3389/fmicb.2020.00078502139HDAC6, A Novel Cargo for Autophagic Clearance of Stress Granules, Mediates the Repression of the Type I Interferon Response During Coxsackievirus A16 InfectionYingcheng Zheng0Yingcheng Zheng1Guoguo Zhu2Yinglian Tang3Yinglian Tang4Jun Yan5Jun Yan6Song Han7Jun Yin8Biwen Peng9Xiaohua He10Wanhong Liu11Wanhong Liu12Hubei Province Key Laboratory of Allergy and Immunology, Department of Immunology, School of Basic Medical Sciences, Wuhan University, Wuhan, ChinaShenzhen Research Institute, Wuhan University, Shenzhen, ChinaDepartment of Emergency, General Hospital of Central Theater Command of People’s Liberation Army of China, Wuhan, ChinaHubei Province Key Laboratory of Allergy and Immunology, Department of Immunology, School of Basic Medical Sciences, Wuhan University, Wuhan, ChinaShenzhen Research Institute, Wuhan University, Shenzhen, ChinaHubei Province Key Laboratory of Allergy and Immunology, Department of Immunology, School of Basic Medical Sciences, Wuhan University, Wuhan, ChinaShenzhen Research Institute, Wuhan University, Shenzhen, ChinaHubei Province Key Laboratory of Allergy and Immunology, Department of Immunology, School of Basic Medical Sciences, Wuhan University, Wuhan, ChinaHubei Province Key Laboratory of Allergy and Immunology, Department of Immunology, School of Basic Medical Sciences, Wuhan University, Wuhan, ChinaHubei Province Key Laboratory of Allergy and Immunology, Department of Immunology, School of Basic Medical Sciences, Wuhan University, Wuhan, ChinaHubei Province Key Laboratory of Allergy and Immunology, Department of Immunology, School of Basic Medical Sciences, Wuhan University, Wuhan, ChinaHubei Province Key Laboratory of Allergy and Immunology, Department of Immunology, School of Basic Medical Sciences, Wuhan University, Wuhan, ChinaShenzhen Research Institute, Wuhan University, Shenzhen, ChinaAutophagic cargoes ensure selective autophagy for the recognition and removal of various cytosolic aggregated proteins, damaged organelles, or pathogens. Stress granules (SGs), as antiviral immune complexes, serve a positive role in the type I interferon (IFN) response and can be targeted by autophagy (termed granulophagy). However, the cargo of granulophagy remains elusive, and it is still unknown whether granulophagy plays a role in viral infection. Here, we found that histone deacetylase 6 (HDAC6), a component of viral RNA-induced SGs, is a novel granulophagic cargo that is recognized by p62/Sequestosome 1 (SQSTM1) and mediates the degradation of SGs in coxsackievirus A16 (CA16)-infected cells. CA16 viral RNA activated the protein kinase RNA-activated (PKR)/eukaryotic translation initiation factor 2-alpha (eIF2α) pathway to promote SG assembly. The SGs were degraded by CA16-triggered autophagy via the interaction between the ubiquitin-associated (UBA) domain of p62 and the ubiquitin-binding domain (UBD) of HDAC6, which was bridged by a poly-ubiquitin chain. We also found that granulophagy repressed the type I interferon response and facilitated viral replication. These results suggest that HDAC6 might be the first identified granulophagic cargo and granulophagy could be a strategy that viruses apply to repress the antiviral immune response.https://www.frontiersin.org/article/10.3389/fmicb.2020.00078/fullautophagystress granuleHDAC6coxsackievirus A16type I interferon response |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yingcheng Zheng Yingcheng Zheng Guoguo Zhu Yinglian Tang Yinglian Tang Jun Yan Jun Yan Song Han Jun Yin Biwen Peng Xiaohua He Wanhong Liu Wanhong Liu |
spellingShingle |
Yingcheng Zheng Yingcheng Zheng Guoguo Zhu Yinglian Tang Yinglian Tang Jun Yan Jun Yan Song Han Jun Yin Biwen Peng Xiaohua He Wanhong Liu Wanhong Liu HDAC6, A Novel Cargo for Autophagic Clearance of Stress Granules, Mediates the Repression of the Type I Interferon Response During Coxsackievirus A16 Infection Frontiers in Microbiology autophagy stress granule HDAC6 coxsackievirus A16 type I interferon response |
author_facet |
Yingcheng Zheng Yingcheng Zheng Guoguo Zhu Yinglian Tang Yinglian Tang Jun Yan Jun Yan Song Han Jun Yin Biwen Peng Xiaohua He Wanhong Liu Wanhong Liu |
author_sort |
Yingcheng Zheng |
title |
HDAC6, A Novel Cargo for Autophagic Clearance of Stress Granules, Mediates the Repression of the Type I Interferon Response During Coxsackievirus A16 Infection |
title_short |
HDAC6, A Novel Cargo for Autophagic Clearance of Stress Granules, Mediates the Repression of the Type I Interferon Response During Coxsackievirus A16 Infection |
title_full |
HDAC6, A Novel Cargo for Autophagic Clearance of Stress Granules, Mediates the Repression of the Type I Interferon Response During Coxsackievirus A16 Infection |
title_fullStr |
HDAC6, A Novel Cargo for Autophagic Clearance of Stress Granules, Mediates the Repression of the Type I Interferon Response During Coxsackievirus A16 Infection |
title_full_unstemmed |
HDAC6, A Novel Cargo for Autophagic Clearance of Stress Granules, Mediates the Repression of the Type I Interferon Response During Coxsackievirus A16 Infection |
title_sort |
hdac6, a novel cargo for autophagic clearance of stress granules, mediates the repression of the type i interferon response during coxsackievirus a16 infection |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Microbiology |
issn |
1664-302X |
publishDate |
2020-01-01 |
description |
Autophagic cargoes ensure selective autophagy for the recognition and removal of various cytosolic aggregated proteins, damaged organelles, or pathogens. Stress granules (SGs), as antiviral immune complexes, serve a positive role in the type I interferon (IFN) response and can be targeted by autophagy (termed granulophagy). However, the cargo of granulophagy remains elusive, and it is still unknown whether granulophagy plays a role in viral infection. Here, we found that histone deacetylase 6 (HDAC6), a component of viral RNA-induced SGs, is a novel granulophagic cargo that is recognized by p62/Sequestosome 1 (SQSTM1) and mediates the degradation of SGs in coxsackievirus A16 (CA16)-infected cells. CA16 viral RNA activated the protein kinase RNA-activated (PKR)/eukaryotic translation initiation factor 2-alpha (eIF2α) pathway to promote SG assembly. The SGs were degraded by CA16-triggered autophagy via the interaction between the ubiquitin-associated (UBA) domain of p62 and the ubiquitin-binding domain (UBD) of HDAC6, which was bridged by a poly-ubiquitin chain. We also found that granulophagy repressed the type I interferon response and facilitated viral replication. These results suggest that HDAC6 might be the first identified granulophagic cargo and granulophagy could be a strategy that viruses apply to repress the antiviral immune response. |
topic |
autophagy stress granule HDAC6 coxsackievirus A16 type I interferon response |
url |
https://www.frontiersin.org/article/10.3389/fmicb.2020.00078/full |
work_keys_str_mv |
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