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. 2021 Nov;595(21):2665-2674.
doi: 10.1002/1873-3468.14200. Epub 2021 Oct 11.

MEK/ERK MAP kinase limits poly I:C-induced antiviral gene expression in RAW264.7 macrophages by reducing interferon-beta expression

Shawn M Freed  1 , Danielle S Baldi  1 , Jason A Snow  1 , Sierra R Athen  1 , Zachary P Guinn  2 , T Scott Pinkerton  1 , Thomas M Petro  2 , Tyler C Moore  1
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MEK/ERK MAP kinase limits poly I:C-induced antiviral gene expression in RAW264.7 macrophages by reducing interferon-beta expression

Shawn M Freed et al. FEBS Lett. 2021 Nov.
Free article

Abstract

Toll-like receptor 3 (TLR3) recognizes viral double-stranded RNA (or the synthetic dsRNA analog poly I:C) and induces a signal transduction pathway that results in activation of transcription factors that induce expression of antiviral genes including type I interferon (IFN-I). Secreted IFN-I positively feeds back to amplify antiviral gene expression. In this report, we study the role of MEK/ERK MAP kinase in modulating antiviral gene expression downstream of TLR3. We find MEK/ERK is a negative regulator of antiviral gene expression by limiting expression of IFN-β. However, MEK/ERK does not limit antiviral responses downstream of the type I interferon receptor. These findings provide insights into regulatory mechanisms of antiviral gene expression and reveal potential targets for modulating antiviral immunity.

Keywords: EGFR; ERK; IRF3; ISG; RAW264.7; TLR3; interferon; poly I:C.

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