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

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...

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Published inPLoS pathogens Vol. 16; no. 6; p. e1008611
Main Authors Cheung, Pak-Hin Hinson, Lee, Tak-Wang Terence, Kew, Chun, Chen, Honglin, Yuen, Kwok-Yung, Chan, Chi-Ping, Jin, Dong-Yan
Format Journal Article
LanguageEnglish
Published San Francisco Public Library of Science 01.06.2020
Public Library of Science (PLoS)
Subjects
Agglomeration
Amino acids
Antiviral drugs
Avian flu
Biology and life sciences
Computer and Information Sciences
Destabilization
Epidemics
Infectious diseases
Influenza
Influenza A
Interferon
Laboratories
Mammals
Medicine and health sciences
Mitochondria
Mortality
Pandemics
Pathogenicity
Pathogens
Proteasomes
Proteins
Respiratory diseases
RNA polymerase
Supervision
Tumor necrosis factor-TNF
Virulence
Virulence factors
Viruses
Hong Kong China
China
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Summary: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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The authors have declared that no competing interests exist.
ISSN:1553-7374
1553-7366
1553-7374
DOI:10.1371/journal.ppat.1008611