Oxygen potentiates antiviral innate immunity by sustaining EGLN1-catalyzed proline hydroxylation of IFR3

Presenter: Professor Wuhan Xiao, Institute of Hydrobiology, Chinese Academy of Sciences. 

Title: Oxygen potentiates antiviral innate immunity by sustaining EGLN1-catalyzed proline hydroxylation of IFR3

Abstract:  Oxygen is essential for aerobic organisms, but little is known about its role in antiviral immunity. Here, we report that during responses to viral infection, the hypoxic conditions repress antiviral responsive genes independently of HIF signaling. EGLN1 was identified as a main mediator of the enhancement exerted by the oxygen on antiviral innate responses. Under sufficient oxygen conditions, EGLN1 sustains its prolyl hydroxylase activity to catalyze hydroxylation of IRF3 at proline 10. This modification potentiates IRF3 phosphorylation, dimerization, and nuclear translocation, resulting in subsequent IRF3 activation. Moreover, mice with deletion of Egln1, treatment with EGLN inhibitor, FG4592, or carrying a Irf3 P10A mutation are more susceptible to viral infections. These findings not only reveal a direct connection between oxygen and antiviral responses, but also provide insights into the mechanisms whereby oxygen regulates innate immunity. 

Bio: Wuhan Xiao, Ph.D., the director of Center for Molecular and Cellular Biology of Aquatic Organisms in Institute of Hydrobiology (IHB), Chinese Academy of Sciences. He obtained Bachelor degree in Wuhan University and Ph. D. degree in IHB. Then he did his postdoc. training in Northwestern University, USA from 1998 to 2006. In 2006, he moved back to IHB and set up his own lab. His lab is interested in molecular mechanisms of hypoxia tolerance and innate immunity in response to viral infection of fish, as well as the crosstalk between hypoxia signaling and innate antiviral immunity.