Details

Autor(en) / Beteiligte

• Cheung, Pak-Hin Hinson
• Lee, Tak-Wang Terence
• Kew, Chun
• Chen, Honglin
• Yuen, Kwok-Yung
• Chan, Chi-Ping
• Jin, Dong-Yan
• Palese, Peter

Titel

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

Ist Teil von

• PLoS pathogens, 2020-06, Vol.16 (6), p.e1008611-e1008611

Ort / Verlag

San Francisco: Public Library of Science

Erscheinungsjahr

2020

Link zum Volltext

Quelle

EZB Free E-Journals

Beschreibungen/Notizen

• 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.