Influenza A virus NS1 induces degradation of sphingosine 1-phosphate lyase to obstruct the host innate immune response

Jennifer J. Wolf, Chuan Xia, Caleb J. Studstill, Hanh Ngo, Steven L. Brody, Paul E. Anderson, Bumsuk Hahm

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)67-75
Number of pages9
JournalVirology
Volume558
DOIs
StatePublished - Jun 2021

Keywords

  • Influenza virus
  • Nonstructural protein 1
  • Protein degradation
  • Sphingosine-1-phosphate lyase
  • Type I interferon
  • Ubiquitination
  • Viral immune evasion

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