RT Journal Article
SR Electronic
T1 African Swine Fever Virus pI215L Negatively Regulates cGAS-STING Signaling Pathway through Recruiting RNF138 to Inhibit K63-Linked Ubiquitination of TBK1
JF The Journal of Immunology
JO J. Immunol.
FD American Association of Immunologists
SP 2754
OP 2769
DO 10.4049/jimmunol.2100320
VO 207
IS 11
A1 Huang, Li
A1 Xu, Wenjie
A1 Liu, Hongyang
A1 Xue, Mengdi
A1 Liu, Xiaohong
A1 Zhang, Kunli
A1 Hu, Liang
A1 Li, Jiangnan
A1 Liu, Xuemin
A1 Xiang, Zhida
A1 Zheng, Jun
A1 Li, Changyao
A1 Chen, Weiye
A1 Bu, Zhigao
A1 Xiong, Tao
A1 Weng, Changjiang
YR 2021
UL http://www.jimmunol.org/content/207/11/2754.abstract
AB ASFV pI215L is the strongest inhibitory effector on the production of type I IFN.pI215L recruits RNF138 to inhibit K63-linked ubiquitination of TBK1.African swine fever is a severe animal infectious disease caused by African swine fever virus (ASFV), and the morbidity and mortality associated with virulent ASFV isolates are as high as 100%. Previous studies showed that the ability of ASFV to antagonize IFN production is closely related to its pathogenicity. Here, we report that ASFV HLJ/18 infection induced low levels of type I IFN and inhibited cGMP-AMP–induced type I IFN production in porcine alveolar macrophages that were isolated from specific pathogen-free Landrace piglets. Subsequently, an unbiased screen was performed to screen the ASFV genes with inhibitory effects on the type I IFN production. ASFV pI215L, a viral E2 ubiquitin–conjugating enzyme, was identified as one of the strongest inhibitory effectors on the production of type I IFN. Knockdown of pI215L expression inhibited ASFV replication and enhanced IFN-β production. However, inhibition of type I IFN production by pI215L was independent of its E2 enzyme activity. Furthermore, we found that pI215L inhibited type I IFN production and K63-linked polyubiquitination of TANK-binding kinase 1 through pI215L-binding RING finger protein 138 (RNF138). ASFV pI215L enhanced the interaction between RNF138 and RNF128 and promoted RNF138 to degrade RNF128, which resulted in reduced K63-linked polyubiquitination of TANK-binding kinase 1 and type І IFN production. Taken together, our findings reveal a novel immune escape mechanism of ASFV, which provides a clue to the design and development of an immune-sensitive attenuated live vaccine.This article is featured in Top Reads, p.