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SNX8 modulates innate immune response to DNA virus by mediating trafficking and activation of MITA.

ABSTRACT: MITA (also called STING) is a central adaptor protein in innate immune response to cytosolic DNA. Cellular trafficking of MITA from the ER to perinuclear microsomes after DNA virus infection is critical for MITA activation and onset of innate antiviral response. Here we found that SNX8 is a component of DNA-triggered induction of downstream effector genes and innate immune response. Snx8-/- mice infected with the DNA virus HSV-1 exhibited lower serum cytokine levels and higher viral titers in the brains, resulting in higher lethality. Mechanistically, SNX8 recruited the class III phosphatylinositol 3-kinase VPS34 to MITA, which is required for trafficking of MITA from the ER to perinuclear microsomes. Our findings suggest that SNX8 is a critical component in innate immune response to cytosolic DNA and DNA virus.

SUBMITTER: Wei J

PROVIDER: S-EPMC6188873 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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SNX8 modulates innate immune response to DNA virus by mediating trafficking and activation of MITA.

Wei Jin J Lian Huan H Guo Wei W Chen Yun-Da YD Zhang Xia-Nan XN Zang Ru R Zhong Li L Yang Qing Q Hu Ming-Ming MM Luo Wei-Wei WW Shu Hong-Bing HB Li Shu S

PLoS pathogens 20181015 10

MITA (also called STING) is a central adaptor protein in innate immune response to cytosolic DNA. Cellular trafficking of MITA from the ER to perinuclear microsomes after DNA virus infection is critical for MITA activation and onset of innate antiviral response. Here we found that SNX8 is a component of DNA-triggered induction of downstream effector genes and innate immune response. Snx8-/- mice infected with the DNA virus HSV-1 exhibited lower serum cytokine levels and higher viral titers in th ...[more]

PMID: 30321235

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