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Dissecting Innate Immune Signaling in Viral Evasion of Cytokine Production
Published on: March 2, 2014
The CD97-PPM1G axis dampens antiviral immunity by dephosphorylating IRF7 in type I interferon pathway
Huasong Chang1, Wenjing Qi1, Rukun Yang1
1Ruminant Diseases Research Center, College of Life Sciences, Shandong Normal University, Jinan, Shandong, China.
None:
The activation of type I interferon (IFN-I) signaling is crucial for defending host cells against viral infections. A comprehensive IFN-I response necessitates the activation of several cellular factors, among them Interferon Regulator Factor 7 (IRF7). Nonetheless, the mechanisms governing IRF7 inactivation in response to viral infection remain largely unknown. Here, we illustrate that Cluster of differentiation 97 (CD97), a G protein-coupled receptor, interacts with PPM1G via intracellular Arg-819 and Arg-822 residues. PPM1G then recruits and dephosphorylates IRF7, leading to its inhibition. CD97-mediated inactivation of IRF7 impedes its translocation into the nucleus and subsequent activation of IFN-I, ultimately promoting the viral replication. Moreover, mice lacking CD97 display heightened resistance to viral infection. The compound sanguinarine (SANG) hinders viral replication by dampening CD97 expression. This study provides a basis for CD97 as a potential antiviral target and SANG as a candidate antiviral small molecule drug.
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