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 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 ? 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.
Mesh Terms:
A549 Cells, Adaptor Proteins, Signal Transducing, Animals, Dogs, HEK293 Cells, Humans, Influenza A Virus, H7N9 Subtype, Influenza, Human, Interferon-beta, Madin Darby Canine Kidney Cells, Mitochondria, Protein Aggregation, Pathological, Signal Transduction, THP-1 Cells, Tripartite Motif Proteins, Ubiquitin-Protein Ligases, Viral Proteins
A549 Cells, Adaptor Proteins, Signal Transducing, Animals, Dogs, HEK293 Cells, Humans, Influenza A Virus, H7N9 Subtype, Influenza, Human, Interferon-beta, Madin Darby Canine Kidney Cells, Mitochondria, Protein Aggregation, Pathological, Signal Transduction, THP-1 Cells, Tripartite Motif Proteins, Ubiquitin-Protein Ligases, Viral Proteins
PLoS Pathog
Date: Dec. 01, 2019
PubMed ID: 32511263
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