SARS-CoV-2 nonstructural protein 6 triggers endoplasmic reticulum stress-induced autophagy to degrade STING1

Pengtao Jiao; Wenhui Fan; Xiaoya Ma; Runshan Lin; Yuna Zhao; Yabo Li; He Zhang; Xiaojuan Jia; Yuhai Bi; Xiaoli Feng; Minghua Li; Wenjun Liu; Ke Zhang; Lei Sun

doi:10.1080/15548627.2023.2238579

SARS-CoV-2 nonstructural protein 6 triggers endoplasmic reticulum stress-induced autophagy to degrade STING1

Autophagy. 2023 Dec;19(12):3113-3131. doi: 10.1080/15548627.2023.2238579. Epub 2023 Jul 23.

Authors

Pengtao Jiao¹, Wenhui Fan¹, Xiaoya Ma^{2

3}, Runshan Lin^{1

3}, Yuna Zhao^{1

4}, Yabo Li^{1

4}, He Zhang⁵, Xiaojuan Jia⁶, Yuhai Bi^{1

3

6}, Xiaoli Feng⁷, Minghua Li⁷, Wenjun Liu^{1

3

4

5}, Ke Zhang², Lei Sun^{1

3}

Affiliations

¹ CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
² Key Laboratory of Molecular Virology and Immunology, Institute Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China.
³ University of Chinese Academy of Sciences, Beijing, China.
⁴ State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources & Laboratory of Animal Infectious Diseases, College of Animal Sciences and Veterinary Medicine, Guangxi University, Nanning, Guangxi, China.
⁵ Institute of Infectious Diseases, Shenzhen Bay Laboratory, Shenzhen, Guangdong, China.
⁶ The Biological Safety Level-3 (BSL-3) Laboratory of Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
⁷ Kunming National High-Level Biosafety Research Center for Non-Human Primates, Center for Biosafety Mega-Science, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China.

Abstract

aa: amino acid; ATF6: activating transcription factor 6; ATG5: autophagy related 5; CCPG1: cell cycle progression 1; CFTR: CF transmembrane conductance regulator; cGAMP: cyclic GMP-AMP; CGAS: cyclic GMP-AMP synthase; CHX: cycloheximide; Co-IP: co-immunoprecipitation; CQ: chloroquine; EIF2A/eIF2α: eukaryotic translation initiation factor 2A; EIF2AK3/PERK: eukaryotic translation initiation factor 2 alpha kinase 3; ER: endoplasmic reticulum; ERN1/IRE1: endoplasmic reticulum to nucleus signaling 1; GFP: green fluorescent protein; HSPA5/GRP78: heat shock protein family A (Hsp70) member 5; HSV-1: herpes simplex virus type 1; IFIT1: interferon induced protein with tetratricopeptide repeats 1; IFNB1/IFN-β: interferon beta 1; IRF3: interferon regulatory factor 3; ISG15: ISG15 ubiquitin like modifier; MAP1LC3B/LC3B: microtubule associated protein 1 light chain 3 beta; MAP3K7/TAK1: mitogen-activated protein kinase kinase kinase 7; MAVS: mitochondrial antiviral signaling protein; MOI: multiplicity of infection; NFKB/NF-κB: nuclear factor kappa B; NSP6: non-structural protein 6; Δ106-108: deletion of amino acids 106-108 in NSP6 of SARS-CoV-2; Δ105-107: deletion of amino acids 105-107 in NSP6 of SARS-CoV-2; RETREG1/FAM134B: reticulophagy regulator 1; RIGI/DDX58: RNA sensor RIG-I; SQSTM1/p62: sequestosome 1; STING1: stimulator of interferon response cGAMP interactor 1; TBK1: TANK binding kinase 1.

Keywords: Autophagy; HSPA5; NSP6; SARS-CoV-2; STING1; endoplasmic reticulum stress.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acids
Autophagy / physiology
COVID-19*
Endoplasmic Reticulum Chaperone BiP
Endoplasmic Reticulum Stress / physiology
Humans
Interferons
SARS-CoV-2*

Substances

Endoplasmic Reticulum Chaperone BiP
Interferons
Amino Acids

Grants and funding

This work was supported by the National Key Research and Development Program of China (2021YFC2600200), the Strategic Priority Research Program of Chinese Academy of Sciences (XDB29010000), the National Natural Science Foundation of China (32170143), and the Special Postdoctoral Researcher Program of the Chinese Academy of Sciences (E1295101).