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Sci Signal. 2019 Mar 19;12(573). pii: eaau4604. doi: 10.1126/scisignal.aau4604.

HIPK2 is necessary for type I interferon-mediated antiviral immunity.

Author information

1
Institute of Systems Biomedicine, Department of Immunology, School of Basic Medical Sciences, Beijing Key Laboratory of Tumor Systems Biology, Peking University Health Science Center, Beijing 100191, China.
2
Section of Infectious Diseases, Yale University School of Medicine, New Haven, CT 208022, USA.
3
Department of Parasitology, Department of Public Health and Preventive Medicine, School of Medicine, Jinan University, No. 601, Huangpu Avenue West, Guangzhou, Guangdong 510632, China.
4
Department of Epidemiology, School of Medicine, Jinan University, Guangzhou 510632, China.
5
Section of Rheumatology, Yale University School of Medicine, New Haven, CT 06510, USA.
6
Department of Immunology, University of Connecticut Health Center, 263 Farmington Ave., Farmington, CT 06030, USA.
7
Section of Infectious Diseases, Yale University School of Medicine, New Haven, CT 208022, USA. fupingyou@hsc.pku.edu.cn erol.fikrig@yale.edu.
8
Howard Hughes Medical Institute, Chevy Chase, MA 20815, USA.
9
Institute of Systems Biomedicine, Department of Immunology, School of Basic Medical Sciences, Beijing Key Laboratory of Tumor Systems Biology, Peking University Health Science Center, Beijing 100191, China. fupingyou@hsc.pku.edu.cn erol.fikrig@yale.edu.

Abstract

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.

PMID:
30890658
DOI:
10.1126/scisignal.aau4604

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