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

PLoS Pathog. 2018 Oct 15;14(10):e1007336. doi: 10.1371/journal.ppat.1007336. eCollection 2018 Oct.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / immunology*
  • Brain / pathology
  • Brain / virology
  • Cytokines / metabolism
  • DNA Virus Infections / immunology*
  • DNA Virus Infections / metabolism
  • DNA Virus Infections / virology
  • DNA Viruses / immunology
  • DNA Viruses / pathogenicity*
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Immunity, Innate / immunology*
  • Membrane Proteins / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Protein Transport
  • Sorting Nexins / physiology*
  • Viral Load

Substances

  • Cytokines
  • Membrane Proteins
  • SNX8 protein, human
  • STING1 protein, human
  • Sorting Nexins

Grants and funding

This work was supported by grants from the State Key R&D Program of China (2017YFA0505800, 2016YFA0502102), and the National Natural Science Foundation of China (31630045, 31521091 and 31671465). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.