Influenza A virus NS1 induces degradation of sphingosine 1-phosphate lyase to obstruct the host innate immune response
| Autor: | Jennifer J. Wolf, Bumsuk Hahm, Paul E. Anderson, Caleb J. Studstill, Hanh Ngo, Steven L. Brody, Chuan Xia |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
viruses
Down-Regulation Protein degradation Viral Nonstructural Proteins medicine.disease_cause Article 03 medical and health sciences chemistry.chemical_compound Downregulation and upregulation Ubiquitin Interferon Virology Influenza Human medicine Influenza A virus otorhinolaryngologic diseases Humans Phosphorylation 030304 developmental biology Aldehyde-Lyases Immune Evasion 0303 health sciences Innate immune system Sphingosine biology Host Microbial Interactions 030302 biochemistry & molecular biology Ubiquitination biochemical phenomena metabolism and nutrition Immunity Innate Cell biology HEK293 Cells chemistry A549 Cells Proteolysis biology.protein sense organs medicine.drug |
| Zdroj: | Virology |
| ISSN: | 1096-0341 |
| Popis: | The type I interferon (IFN)-mediated innate immune response is one of the central obstacles influenza A virus (IAV) must overcome in order to successfully replicate within the host. We have previously shown that sphingosine 1-phosphate (S1P) lyase (SPL) enhances IKKϵ-mediated type I IFN responses. Here, we demonstrate that the nonstructural protein 1 (NS1) of IAV counteracts the SPL-mediated antiviral response by inducing degradation of SPL. SPL was ubiquitinated and downregulated upon IAV infection or NS1 expression, whereas NS1-deficient IAV failed to elicit SPL ubiquitination or downregulation. Transiently overexpressed SPL increased phosphorylation of IKKϵ, resulting in enhanced expression of type I IFNs. However, this induction was markedly inhibited by IAV NS1. Collectively, this study reveals a novel strategy employed by IAV to subvert the type I IFN response, providing new insights into the interplay between IAV and host innate immunity. |
| Databáze: | OpenAIRE |
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