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


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.

SUBMITTER: Cao L 

PROVIDER: S-EPMC6893850 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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

Cao Lili L   Yang Guang G   Gao Shandian S   Jing Chunxia C   Montgomery Ruth R RR   Yin Yuxin Y   Wang Penghua P   Fikrig Erol E   You Fuping F  

Science signaling 20190319 573


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 c  ...[more]

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