Time: March 21, 2019
Source: School of Medical

The Department of Pathogen Biology in JNU's School of Medicine, the Peking University Institute of Systems Biomedicine and the Yale School of Medicine's Department of Infectious Diseases unveiled their joint research results in a cover article, HIPK2 is necessary for type I interferon-mediated antiviral immunity, published March 19 in Science Signaling, part of the Science Family of Journals.

 (Their cooperative research results were published as the cover article in Science Signaling.)   

Precise control of interferons (IFNs) is crucial to maintain immune homeostasis. Here, we demonstrated that homeodomain-interacting protein kinase 2 (HIPK2) was required for the production of type I IFNs in response to RNA virus infection. HIPK2 deficiency markedly impaired IFN production in macrophages after vesicular stomatitis virus (VSV) infection, and HIPK2-deficient mice were more susceptible to lethal VSV disease than were wild-type mice. After VSV infection, HIPK2 was cleaved by active caspases, which released a hyperactive, N-terminal fragment that translocated to the nucleus and further augmented antiviral responses. In part, HIPK2 interacted with ELF4 and promoted its phosphorylation at Ser369, which enabled Ifn-b transcription. In addition, HIPK2 production was stimulated by type I IFNs to further enhance antiviral immunity. These data suggest that the kinase activity and nuclear localization of HIPK2 are essential for the production of type I IFNs.

The corresponding authors are You Fuping, a JNU guest professor and Peking University researcher, and Prof. Erol Fikrig, section chief of Yale`s Department of Infectious Diseases and a researcher in the Howard Hughes Medical Institute. Joint head authors are Dr. Cao Lili of Peking University and Prof. Yang Guang of the JNU School of Medicine's Department of Pathogen Biology. Co-author is Prof. Jing Chunxia of JNU's School of Medicine's Department of Public Health and Preventive Medicine.

(The antiviral mechanism of HIPK2)
Link: http://stke.sciencemag.org/content/12/573/eaau4604