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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    <subfield code="a">Type 1 interferons (IFNα/β) mediate immunologic host resistance to
numerous viral infections including herpes simplex virus type 1 (HSV-1). The
pathways responsible for maintenance of IFNα/β signaling during the innate
immune response to acute HSV-1 infection in the cornea are incompletely
understood. Using a murine ocular infection model, we hypothesized that the
stimulator of IFN genes (STING) mediates host resistance to HSV-1 infection in
the external ocular surface and preserves the structural integrity of this immune
privileged mucosal site. Viral pathogenesis, tissue pathology, and host immune
responses during ocular HSV-1 infection were evaluated and characterized by
plaque assay, esthesiometry, pachymetry, immunohistochemistry, flow
cytometry, and siRNA transfection in wildtype C57BL/6 (WT), STING-deficient
(STING-/-), and IFNα/β receptor-deficient (CD118-/-) mice at days 3-5 post
infection (pi). The presence of STING was critical for sustained control of HSV-1
replication in the corneal epithelium and neuroinvasion, but loss of STING had a
negligible impact with respect to gross tissue pathology. Auxiliary STING
independent IFNα/β signaling pathways were responsible for maintenance of the
corneal integrity. Lymphatic vessels, mast cells, and sensory innervation were
compromised in CD118-/- mice concurrent with increased tissue edema. STING
dependent signaling led to the upregulation of tetherin, a viral restriction factor
we identify to be important in containing the spread of HSV-1 in vivo.</subfield>
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    <subfield code="a">10.1038/mi.2015.124</subfield>
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