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Influenza A virus protein PA‐X suppresses host Ankrd17‐mediated immune responses
Author(s) -
Li Mai,
Qi Wenbao,
Chang Qing,
Chen Ruohong,
Zhen Danlin,
Liao Ming,
Wen Jikai,
Deng Yiqun
Publication year - 2021
Publication title -
microbiology and immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.664
H-Index - 70
eISSN - 1348-0421
pISSN - 0385-5600
DOI - 10.1111/1348-0421.12863
Subject(s) - biology , ankyrin repeat , immune system , innate immune system , influenza a virus , virus , virology , microbiology and biotechnology , immunology , gene , genetics
Influenza A virus (IAV) PA‐X is a critical ribonuclease protein involved in host cell shutoff but its role in modulating the host immune response to IAV infection remains to be addressed. In this study, host cellular proteins that directly interact with PA‐X were screened to investigate the biological function of PA‐X in the pathogenesis of IAV infection. The protein ankyrin repeat domain 17 (Ankrd17), a positive regulator of inflammatory responses via the retinoic acid‐inducible gene‐I (RIG‐I)‐like receptor (RLR) signaling pathway, was identified as a specific PA‐X binding partner that preferred PA‐X to the PA protein. The N‐terminal ankyrin repeats of Ankrd17 are the key domain for the interaction with PA‐X rather than PA, which is required for the function of Ankrd17 in elevating the host immune response. Using Ankrd17 knockout and overexpression, we confirmed that PA‐X significantly affected the Ankrd17‐mediated response to infection in host cells. Our data therefore reveal a novel function for PA‐X in the regulation of innate immune pathways via the interaction between PA‐X and Ankrd17.