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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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<oai_dc:dc xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:oai_dc="http://www.openarchives.org/OAI/2.0/oai_dc/" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xsi:schemaLocation="http://www.openarchives.org/OAI/2.0/oai_dc/ http://www.openarchives.org/OAI/2.0/oai_dc.xsd">
  <dc:creator>Royer, D. J.</dc:creator>
  <dc:creator>Carr, D. J. J.</dc:creator>
  <dc:date>2015-12-02</dc:date>
  <dc:description>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.</dc:description>
  <dc:identifier>https://zenodo.org/record/883748</dc:identifier>
  <dc:identifier>10.1038/mi.2015.124</dc:identifier>
  <dc:identifier>oai:zenodo.org:883748</dc:identifier>
  <dc:rights>info:eu-repo/semantics/openAccess</dc:rights>
  <dc:title>A STING-dependent innate-sensing pathway mediates resistance to corneal HSV-1 infection via upregulation of the antiviral effector tetherin</dc:title>
  <dc:type>info:eu-repo/semantics/article</dc:type>
  <dc:type>publication-article</dc:type>
</oai_dc:dc>
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