Influenza PB1-F2 Inhibits Avian MAVS Signaling
| Autor: | Domingo Miranzo-Navarro, Ximena Fleming-Canepa, Katharine E. Magor, David G. Tetrault, Chase A Stevens, Adam Moghrabi, Yanna Xiao, Danyel Evseev |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
animal structures duck Receptors Retinoic Acid viruses lcsh:QR1-502 NS1 Chicken Cells medicine.disease_cause lcsh:Microbiology Article Virus RIG-I Viral Proteins 03 medical and health sciences Influenza A Virus H1N1 Subtype 0302 clinical medicine Ubiquitin Virology PB1-F2 medicine Influenza A virus Animals Humans Mutation Innate immune system biology Ubiquitination virus diseases Signal transducing adaptor protein Fibroblasts biochemical phenomena metabolism and nutrition MAVS Immunity Innate Mitochondria 3. Good health Cell biology CARD Signaling Adaptor Proteins Ducks HEK293 Cells 030104 developmental biology Infectious Diseases innate immune response biology.protein type I interferon Chickens Signal Transduction 030215 immunology |
| Zdroj: | Viruses Volume 12 Issue 4 Viruses, Vol 12, Iss 409, p 409 (2020) |
| ISSN: | 1999-4915 |
| DOI: | 10.3390/v12040409 |
| Popis: | RIG-I plays an essential role in the duck innate immune response to influenza infection. RIG-I engages the critical adaptor protein mitochondrial antiviral signaling (MAVS) to activate the downstream signaling pathway. The influenza A virus non-structural protein PB1-F2 interacts with MAVS in human cells to inhibit interferon production. As duck and human MAVS share only 28% amino acid similarity, it is not known whether the influenza virus can similarly inhibit MAVS signaling in avian cells. Using confocal microscopy we show that MAVS and the constitutively active N-terminal end of duck RIG-I (2CARD) co-localize in DF-1 cells, and duck MAVS is pulled down with GST-2CARD. We establish that either GST-2CARD, or duck MAVS can initiate innate signaling in chicken cells and their co-transfection augments interferon-beta promoter activity. Demonstrating the limits of cross-species interactions, duck RIG-I 2CARD initiates MAVS signaling in chicken cells, but works poorly in human cells. The D122A mutation of human 2CARD abrogates signaling by affecting MAVS engagement, and the reciprocal A120D mutation in duck 2CARD improves signaling in human cells. We show mitochondrial localization of PB1-F2 from influenza A virus strain A/Puerto Rico/8/1934 (H1N1 PR8), and its co-localization and co-immunoprecipitation with duck MAVS. PB1-F2 inhibits interferon-beta promoter activity induced by overexpression of either duck RIG-I 2CARD, full-length duck RIG-I, or duck MAVS. Finally, we show that the effect of PB1-F2 on mitochondria abrogates TRIM25-mediated ubiquitination of RIG-I CARD in both human and avian cells, while an NS1 variant from the PR8 influenza virus strain does not. |
| Databáze: | OpenAIRE |
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