African Swine Fever Virus MGF-505-7R Negatively Regulates cGAS-STING-Mediated Signaling Pathway.

Abstract

African swine fever virus (ASFV) is a devastating infectious disease in pigs, severely threatening the global pig industry. To efficiently infect animals, ASFV must evade or inhibit fundamental elements of the innate immune system, namely the type I IFN response. In this study, we identified that ASFV MGF-505-7R protein exerts a negative regulatory effect on STING-dependent antiviral responses. MGF-505-7R interacted with STING and inhibited the cGAS-STING signaling pathway at STING level. MGF-505-7R overexpression either degraded STING or STING expression was reduced in ASFV-infected cells via autophagy, whereas STING expression was elevated in MGF-505-7R-deficient ASFV-infected cells. We further found that MGF-505-7R promoted the expression of the autophagy-related protein ULK1 to degrade STING, whereas ULK1 was elevated in MGF-505-7R-deficient ASFV-infected cells. Moreover, MGF-505-7R-deficient ASFV induced more IFN-β production than wild-type ASFV and was attenuated in replication compared with wild-type ASFV. The replicative ability of MGF-505-7R-deficient ASFV was also attenuated compared with wild-type. Importantly, MGF-505-7R-deficient ASFV was fully attenuated in pigs. Our results showed for the first time, to our knowledge, a relationship involving the cGAS-STING pathway and ASFV MGF-505-7R, contributing to uncover the molecular mechanisms of ASFV virulence and to the rational development of ASFV vaccines.

• Authors: Dan Li, Wenping Yang, Lulu Li, Pan Li, Zhao Ma, Jing Zhang, Xiaolan Qi, Jingjing Ren, Yi Ru, Qingli Niu, Zhijie Liu, Xiangtao Liu, Haixue Zheng
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 206 Issue 8 Pg. 1844-1857 (04 15 2021) ISSN: 1550-6606 [Electronic] United States
• PMID: 33712518 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Comment)
• Copyright: Copyright © 2021 by The American Association of Immunologists, Inc.

Chemical References

• Viral Proteins
• Nucleotidyltransferases

Topics

• African Swine Fever Virus (genetics, metabolism)
• Animals
• Nucleotidyltransferases (genetics, metabolism)
• Signal Transduction
• Swine
• Viral Proteins
• Virulence