Research Team Led By Prof. Cao Xuetao Publishes Article on Amplifier of IFNα Antiviral Immunity in Cell


    In the case of viral intrusion, interferon is the most essential cytokine in our body to protect our health. The research team, led by Prof. Cao Xuetao, a scientist of immunology at Zhejiang University, has located a type of protein which can enormously enhance the antiviral effect of interferon and thereby promote the capability of fighting against various viruses. The study titled “Methyltransferase SETD2-Mediated Methylation of STAT1 Is Critical for Interferon Antiviral Activity” was published in one of the top scientific journal Cell.

    Interferon-α (IFNα) signaling is essential for antiviral response via induction of IFN-stimulated genes (ISGs). Through a non-biased high-throughput RNAi screening of 711 known epigenetic modifiers in cellular models of IFNα-mediated inhibition of HBV replication, the research team identified methyltransferase SETD2 as a critical amplifier of IFNα-mediated antiviral immunity. Conditional knockout mice with hepatocyte-specific deletion of SETD2 exhibit enhanced HBV infection. Mechanistically, SETD2 directly mediates STAT1 methylation on lysine 525 via its methyltransferase activity, which reinforces IFN-activated STAT1 phosphorylation and antiviral cellular response. In addition, SETD2 selectively catalyzes the tri-methylation of H3K36 on promoters of some ISGs such as ISG15, leading to gene activation.

    This study identifies STAT1 methylation on K525 catalyzed by the methyltransferase SETD2 as an essential signaling event for IFNα-dependent antiviral immunity and indicates potential of SETD2 in controlling viral infections. It opens up new approaches to researching into immunological modulation.