Journal article Open Access

A STING-dependent innate-sensing pathway mediates resistance to corneal HSV-1 infection via upregulation of the antiviral effector tetherin

Royer, D. J.; Carr, D. J. J.


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{
  "DOI": "10.1038/mi.2015.124", 
  "author": [
    {
      "family": "Royer, D. J."
    }, 
    {
      "family": "Carr, D. J. J."
    }
  ], 
  "issued": {
    "date-parts": [
      [
        2015, 
        12, 
        2
      ]
    ]
  }, 
  "abstract": "Type 1 interferons (IFN\u03b1/\u03b2) mediate immunologic host resistance to\nnumerous viral infections including herpes simplex virus type 1 (HSV-1). The\npathways responsible for maintenance of IFN\u03b1/\u03b2 signaling during the innate\nimmune response to acute HSV-1 infection in the cornea are incompletely\nunderstood. Using a murine ocular infection model, we hypothesized that the\nstimulator of IFN genes (STING) mediates host resistance to HSV-1 infection in\nthe external ocular surface and preserves the structural integrity of this immune\nprivileged mucosal site. Viral pathogenesis, tissue pathology, and host immune\nresponses during ocular HSV-1 infection were evaluated and characterized by\nplaque assay, esthesiometry, pachymetry, immunohistochemistry, flow\ncytometry, and siRNA transfection in wildtype C57BL/6 (WT), STING-deficient\n(STING-/-), and IFN\u03b1/\u03b2 receptor-deficient (CD118-/-) mice at days 3-5 post\ninfection (pi). The presence of STING was critical for sustained control of HSV-1\nreplication in the corneal epithelium and neuroinvasion, but loss of STING had a\nnegligible impact with respect to gross tissue pathology. Auxiliary STING\nindependent IFN\u03b1/\u03b2 signaling pathways were responsible for maintenance of the\ncorneal integrity. Lymphatic vessels, mast cells, and sensory innervation were\ncompromised in CD118-/- mice concurrent with increased tissue edema. STING\ndependent signaling led to the upregulation of tetherin, a viral restriction factor\nwe identify to be important in containing the spread of HSV-1 in vivo.", 
  "title": "A STING-dependent innate-sensing pathway mediates resistance to corneal HSV-1 infection via upregulation of the antiviral effector tetherin", 
  "type": "article-journal", 
  "id": "883748"
}
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