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...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2020-06-01
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| Series: | PLoS Pathogens |
| Online Access: | https://doi.org/10.1371/journal.ppat.1008611 |
| _version_ | 1818717030173376512 |
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| author | Pak-Hin Hinson Cheung Tak-Wang Terence Lee Chun Kew Honglin Chen Kwok-Yung Yuen Chi-Ping Chan Dong-Yan Jin |
| author_facet | Pak-Hin Hinson Cheung Tak-Wang Terence Lee Chun Kew Honglin Chen Kwok-Yung Yuen Chi-Ping Chan Dong-Yan Jin |
| author_sort | Pak-Hin Hinson Cheung |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-17T19:28:40Z |
| format | Article |
| id | doaj.art-fccd3d1047644b83b2956f4ec4916173 |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2024-12-17T19:28:40Z |
| publishDate | 2020-06-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj.art-fccd3d1047644b83b2956f4ec49161732022-12-21T21:35:20ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742020-06-01166e100861110.1371/journal.ppat.1008611Virus subtype-specific suppression of MAVS aggregation and activation by PB1-F2 protein of influenza A (H7N9) virus.Pak-Hin Hinson CheungTak-Wang Terence LeeChun KewHonglin ChenKwok-Yung YuenChi-Ping ChanDong-Yan JinHuman 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.https://doi.org/10.1371/journal.ppat.1008611 |
| spellingShingle | Pak-Hin Hinson Cheung Tak-Wang Terence Lee Chun Kew Honglin Chen Kwok-Yung Yuen Chi-Ping Chan Dong-Yan Jin Virus subtype-specific suppression of MAVS aggregation and activation by PB1-F2 protein of influenza A (H7N9) virus. PLoS Pathogens |
| title | Virus subtype-specific suppression of MAVS aggregation and activation by PB1-F2 protein of influenza A (H7N9) virus. |
| title_full | Virus subtype-specific suppression of MAVS aggregation and activation by PB1-F2 protein of influenza A (H7N9) virus. |
| title_fullStr | Virus subtype-specific suppression of MAVS aggregation and activation by PB1-F2 protein of influenza A (H7N9) virus. |
| title_full_unstemmed | Virus subtype-specific suppression of MAVS aggregation and activation by PB1-F2 protein of influenza A (H7N9) virus. |
| title_short | Virus subtype-specific suppression of MAVS aggregation and activation by PB1-F2 protein of influenza A (H7N9) virus. |
| title_sort | virus subtype specific suppression of mavs aggregation and activation by pb1 f2 protein of influenza a h7n9 virus |
| url | https://doi.org/10.1371/journal.ppat.1008611 |
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