Article ; Online: RIPK3 interacts with MAVS to regulate type I IFN-mediated immunity to Influenza A virus infection.
2017 Volume 13, Issue 4, Page(s) e1006326
Abstract: ... indicate a novel role for RIPK3 in regulating Mφ-mediated type I IFN anti-viral immunity, independent ... involved in anti-viral immunity. However, the exact role of RIPK3 in immunity to Influenza A Virus (IAV) is ... viral infection and thus requires refined regulatory mechanisms. RIPK3-mediated necroptosis has been shown to be ...
| Abstract | The type I interferon pathway plays a critical role in both host defense and tolerance against viral infection and thus requires refined regulatory mechanisms. RIPK3-mediated necroptosis has been shown to be involved in anti-viral immunity. However, the exact role of RIPK3 in immunity to Influenza A Virus (IAV) is poorly understood. In line with others, we, herein, show that Ripk3-/- mice are highly susceptible to IAV infection, exhibiting elevated pulmonary viral load and heightened morbidity and mortality. Unexpectedly, this susceptibility was linked to an inability of RIKP3-deficient macrophages (Mφ) to produce type I IFN in the lungs of infected mice. In Mφ infected with IAV in vitro, we found that RIPK3 regulates type I IFN both transcriptionally, by interacting with MAVS and limiting RIPK1 interaction with MAVS, and post-transcriptionally, by activating protein kinase R (PKR)-a critical regulator of IFN-β mRNA stability. Collectively, our findings indicate a novel role for RIPK3 in regulating Mφ-mediated type I IFN anti-viral immunity, independent of its conventional role in necroptosis. |
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| MeSH term(s) | Adaptor Proteins, Signal Transducing/genetics ; Adaptor Proteins, Signal Transducing/metabolism ; Animals ; Humans ; Influenza A virus/genetics ; Influenza A virus/physiology ; Influenza, Human/genetics ; Influenza, Human/immunology ; Influenza, Human/metabolism ; Influenza, Human/virology ; Interferon-beta/genetics ; Interferon-beta/immunology ; Macrophages/immunology ; Mice ; Mice, Inbred C57BL ; Protein Binding ; Receptor-Interacting Protein Serine-Threonine Kinases/genetics ; Receptor-Interacting Protein Serine-Threonine Kinases/metabolism |
| Chemical Substances | Adaptor Proteins, Signal Transducing ; IPS-1 protein, mouse ; Interferon-beta (77238-31-4) ; Receptor-Interacting Protein Serine-Threonine Kinases (EC 2.7.11.1) ; Ripk3 protein, mouse (EC 2.7.11.1) |
| Language | English |
| Publishing date | 2017-04 |
| Publishing country | United States |
| Document type | Journal Article |
| ZDB-ID | 2205412-1 |
| ISSN | 1553-7374 ; 1553-7366 |
| ISSN (online) | 1553-7374 |
| ISSN | 1553-7366 |
| DOI | 10.1371/journal.ppat.1006326 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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