African swine fever virus MGF360-4L protein attenuates type I interferon response by suppressing the phosphorylation of IRF3

African swine fever (ASF) is a highly contagious and lethal disease of swine caused by African swine fever virus (ASFV), and the mortality rate caused by virulent stains can approach 100%. Many ASFV viral proteins suppress the interferon production to evade the host's innate immune responses. H...

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Bibliographic Details
Published in:Frontiers in immunology 2024-09, Vol.15, p.1382675
Main Authors: Wang, Zhen, He, Yuheng, Huang, Ying, Zhai, Wenzhu, Tao, Chunhao, Chu, Yuanyuan, Pang, Zhongbao, Zhu, Hongfei, Zhao, Peng, Jia, Hong
Format: Article
Language:English
Subjects:
African Swine Fever - immunology
African Swine Fever - virology
African swine fever virus
African Swine Fever Virus - immunology
Animals
HEK293 Cells
Host-Pathogen Interactions - immunology
Humans
Immune Evasion
Immunity, Innate
Interferon Regulatory Factor-3 - metabolism
Interferon Type I - metabolism
Membrane Proteins - genetics
Membrane Proteins - metabolism
MGF360-4L
Nucleotidyltransferases - metabolism
Phosphorylation
Signal Transduction
suppress
Swine
type I interferon
Viral Proteins - metabolism
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Summary:African swine fever (ASF) is a highly contagious and lethal disease of swine caused by African swine fever virus (ASFV), and the mortality rate caused by virulent stains can approach 100%. Many ASFV viral proteins suppress the interferon production to evade the host's innate immune responses. However, whether ASFV MGF360-4L could inhibit type I interferon (IFN-I) signaling pathway and the underlying molecular mechanisms remain unknown. Our study, indicated that ASFV MGF360-4L could negatively regulates the cGAS-STING mediated IFN-I signaling pathway. Overexpressing ASFV MGF360-4L could inhibit the cGAS/STING signaling pathway by inhibiting the interferon-β promoter activity, which was induced by cGAS/STING, TBK1, and IRF3-5D, and further reduced the transcriptional levels of ISG15, ISG54, ISG56, STAT1, STAT2, and TYK2. Confocal microscopy and immunoprecipitation revealed that MGF360-4L co-localized and interacted with IRF3, and WB revealed that ASFV MGF360-4L suppressed the phosphorylation of IRF3. 4L-F2 (75-162 aa) and 4L-F3 (146-387 aa) were the crucial immunosuppressive domains and sites. Altogether, our study reveals ASFV MGF360-4L inhibited cGAS-STING mediated IFN-I signaling pathways, which provides insights into an evasion strategy of ASFV involving in host's innate immune responses.
ISSN:1664-3224
1664-3224
DOI:10.3389/fimmu.2024.1382675