Virus subtype-specific suppression of MAVS aggregation and activation by PB1-F2 protein of influenza A (H7N9) virus

PLoS Pathogens
Pak-Hin Hinson CheungDong-Yan Jin

Abstract

Human infection with avian influenza A (H5N1) and (H7N9) viruses causes severe respiratory diseases. PB1-F2 protein is a critical virulence factor that suppresses early type I interferon response, but the mechanism of its action in relation to high pathogenicity is not well understood. Here we show that PB1-F2 protein of H7N9 virus is a particularly potent suppressor of antiviral signaling through formation of protein aggregates on mitochondria and inhibition of TRIM31-MAVS interaction, leading to prevention of K63-polyubiquitination and aggregation of MAVS. Unaggregated MAVS accumulated on fragmented mitochondria is prone to degradation by both proteasomal and lysosomal pathways. These properties are proprietary to PB1-F2 of H7N9 virus but not shared by its counterpart in WSN virus. A recombinant virus deficient of PB1-F2 of H7N9 induces more interferon β in infected cells. Our findings reveal a subtype-specific mechanism for destabilization of MAVS and suppression of interferon response by PB1-F2 of H7N9 virus.

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Citations

Jan 20, 2021·Cellular & Molecular Immunology·Koji OnomotoMitsutoshi Yoneyama
Apr 4, 2021·Life·Srikanth Elesela, Nicholas W Lukacs
May 1, 2021·Viruses·Sabrina Weis, Aartjan J W Te Velthuis
Jun 29, 2021·Frontiers in Immunology·Xiuzhi JiaWei Zhao
Jul 18, 2021·Biochimie·A A ShaldzhyanV V Egorov

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Methods Mentioned

BETA
protein
solubility assay
confocal microscopy
transfection
co-immunoprecipitation
Co-immunoprecipitation assay
ubiquitination
immunoprecipitation
immunoprecipitation assay

Software Mentioned

PASTA
Clustal Omega

Related Concepts