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

	SARS-CoV-2 nonstructural protein 6 triggers endoplasmic reticulum stress-induced autophagy to degrade STING1
	Jiao, PT; Fan, WH; Ma, XY; Lin, RS; Zhao, YA; Li, YB; Zhang, H; Jia, XJ; Bi, YH; Feng, XL; Li, MH; Liu, WJ; Zhang, K; Sun, L
	2023
发表期刊	AUTOPHAGY
ISSN	1554-8627
卷号	19 期号:12 页码:3113-3131
摘要	SARS-CoV-2 poses a substantial global threat owing to the emergence of several highly transmissible variants. Autophagy is an intracellular degradation process that maintains cellular homeostasis and combats the invading pathogens. SARS-CoV-2 can trigger autophagy and antagonize interferon production. However, the underlying mechanisms remain elusive, particularly for different variants. Here, we found that SARS-CoV-2 nonstructural protein (NSP) 6 inhibited interferon production by promoting macroautophagy/autophagy-mediated STING1 degradation. Mechanistically, NSP6 induced endoplasmic reticulum stress and bound to HSPA5/GRP78, leading to the activation of EIF2AK3/PERK-EIF2A/EIf2 & alpha; pathway-mediated autophagy, which was associated with lysosomal degradation of STING1 and downregulation of interferon production. Moreover, the 81-120 amino acid (aa) region of NSP6 is critical for autophagy induction and STING1 degradation. Interestingly, NSP6 harboring a three aa deletion in the 81-120 aa region of some SARS-CoV-2 variants led to reduced autophagy, STING1 degradation, and increased host antiviral immunity. Collectively, this study demonstrated a major function of NSP6 in the SARS-CoV-2 evasion of host antiviral immunity by triggering endoplasmic reticulum stress-induced autophagy to degrade STING1 and that enhancement of host antiviral immunity induced by NSP6 variants with a three-aa deletion might be responsible for the attenuation of SARS-CoV-2 variants.
收录类别	SCI
语种	英语
文献类型	期刊论文
条目标识符	http://ir.kiz.ac.cn/handle/152453/14387
专题	管理、支撑部门_高等级生物安全灵长类动物实验中心
推荐引用方式 GB/T 7714	Jiao, PT,Fan, WH,Ma, XY,et al. SARS-CoV-2 nonstructural protein 6 triggers endoplasmic reticulum stress-induced autophagy to degrade STING1[J]. AUTOPHAGY,2023,19(12):3113-3131.
APA	Jiao, PT.,Fan, WH.,Ma, XY.,Lin, RS.,Zhao, YA.,...&Sun, L.(2023).SARS-CoV-2 nonstructural protein 6 triggers endoplasmic reticulum stress-induced autophagy to degrade STING1.AUTOPHAGY,19(12),3113-3131.
MLA	Jiao, PT,et al."SARS-CoV-2 nonstructural protein 6 triggers endoplasmic reticulum stress-induced autophagy to degrade STING1".AUTOPHAGY 19.12(2023):3113-3131.

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