tetano
Editor, Senior Moderator
Virology
. 2021 Mar 13;558:67-75.
doi: 10.1016/j.virol.2021.02.006. Online ahead of print.
Influenza A virus NS1 induces degradation of sphingosine 1-phosphate lyase to obstruct the host innate immune response
Jennifer J Wolf[SUP] 1 [/SUP], Chuan Xia[SUP] 2 [/SUP], Caleb J Studstill[SUP] 1 [/SUP], Hanh Ngo[SUP] 1 [/SUP], Steven L Brody[SUP] 3 [/SUP], Paul E Anderson[SUP] 4 [/SUP], Bumsuk Hahm[SUP] 5 [/SUP]
Affiliations
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 IKK?-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 IKK?, 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.
Keywords: Influenza virus; Nonstructural protein 1; Protein degradation; Sphingosine-1-phosphate lyase; Type I interferon; Ubiquitination; Viral immune evasion.
. 2021 Mar 13;558:67-75.
doi: 10.1016/j.virol.2021.02.006. Online ahead of print.
Influenza A virus NS1 induces degradation of sphingosine 1-phosphate lyase to obstruct the host innate immune response
Jennifer J Wolf[SUP] 1 [/SUP], Chuan Xia[SUP] 2 [/SUP], Caleb J Studstill[SUP] 1 [/SUP], Hanh Ngo[SUP] 1 [/SUP], Steven L Brody[SUP] 3 [/SUP], Paul E Anderson[SUP] 4 [/SUP], Bumsuk Hahm[SUP] 5 [/SUP]
Affiliations
- PMID: 33730651
- DOI: 10.1016/j.virol.2021.02.006
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 IKK?-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 IKK?, 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.
Keywords: Influenza virus; Nonstructural protein 1; Protein degradation; Sphingosine-1-phosphate lyase; Type I interferon; Ubiquitination; Viral immune evasion.