tetano
Editor, Senior Moderator
Cell Rep
. 2021 Jan 19;34(3):108627.
doi: 10.1016/j.celrep.2020.108627.
Critical role of Syk-dependent STAT1 activation in innate antiviral immunity
Shasha Liu[SUP] 1 [/SUP], Yuan Liao[SUP] 2 [/SUP], Biao Chen[SUP] 1 [/SUP], Yuhai Chen[SUP] 3 [/SUP], Ziding Yu[SUP] 2 [/SUP], Haitao Wei[SUP] 3 [/SUP], Lianfeng Zhang[SUP] 4 [/SUP], Shile Huang[SUP] 5 [/SUP], Paul B Rothman[SUP] 6 [/SUP], George Fu Gao[SUP] 3 [/SUP], Ji-Long Chen[SUP] 7 [/SUP]
Affiliations
Abstract
The JAK/STAT1 pathway is generally activated by cytokines, providing essential antiviral defense. Here, we identify that STAT1 activation is independent of cytokines and JAKs at the early infection stage of some viruses, including influenza A virus (IAV). Instead, STAT1 is activated mainly through spleen tyrosine kinase (Syk) downstream of retinoic acid-inducible gene-I/mitochondrial antiviral-signaling protein (RIG-I/MAVS) signaling. Syk deletion profoundly impairs immediate innate immunity, as evidenced by the finding that Syk deletion attenuates tyrosine phosphorylation of STAT1 and reduces the expressions of interferon-stimulated genes (ISGs) in vitro and in vivo. The antiviral response to IAV infection is also significantly suppressed in the STAT1[SUP]Y701F[/SUP] knockin mice. The results demonstrate that STAT1 activation is dependent on Syk rather than the cytokine-activated JAK signaling at the early stage of viral infection, which is critical for initial antiviral immunity. Our finding provides insights into the complicated mechanisms underlying host immune responses to viral infection.
Keywords: MAVS; RIG-I; STAT1; Syk; cytokine; influenza virus; innate immunity.
. 2021 Jan 19;34(3):108627.
doi: 10.1016/j.celrep.2020.108627.
Critical role of Syk-dependent STAT1 activation in innate antiviral immunity
Shasha Liu[SUP] 1 [/SUP], Yuan Liao[SUP] 2 [/SUP], Biao Chen[SUP] 1 [/SUP], Yuhai Chen[SUP] 3 [/SUP], Ziding Yu[SUP] 2 [/SUP], Haitao Wei[SUP] 3 [/SUP], Lianfeng Zhang[SUP] 4 [/SUP], Shile Huang[SUP] 5 [/SUP], Paul B Rothman[SUP] 6 [/SUP], George Fu Gao[SUP] 3 [/SUP], Ji-Long Chen[SUP] 7 [/SUP]
Affiliations
- PMID: 33472080
- DOI: 10.1016/j.celrep.2020.108627
Abstract
The JAK/STAT1 pathway is generally activated by cytokines, providing essential antiviral defense. Here, we identify that STAT1 activation is independent of cytokines and JAKs at the early infection stage of some viruses, including influenza A virus (IAV). Instead, STAT1 is activated mainly through spleen tyrosine kinase (Syk) downstream of retinoic acid-inducible gene-I/mitochondrial antiviral-signaling protein (RIG-I/MAVS) signaling. Syk deletion profoundly impairs immediate innate immunity, as evidenced by the finding that Syk deletion attenuates tyrosine phosphorylation of STAT1 and reduces the expressions of interferon-stimulated genes (ISGs) in vitro and in vivo. The antiviral response to IAV infection is also significantly suppressed in the STAT1[SUP]Y701F[/SUP] knockin mice. The results demonstrate that STAT1 activation is dependent on Syk rather than the cytokine-activated JAK signaling at the early stage of viral infection, which is critical for initial antiviral immunity. Our finding provides insights into the complicated mechanisms underlying host immune responses to viral infection.
Keywords: MAVS; RIG-I; STAT1; Syk; cytokine; influenza virus; innate immunity.