Journal article Open Access
Royer, D. J.; Carr, D. J. J.
<?xml version='1.0' encoding='utf-8'?> <resource xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns="http://datacite.org/schema/kernel-4" xsi:schemaLocation="http://datacite.org/schema/kernel-4 http://schema.datacite.org/meta/kernel-4.1/metadata.xsd"> <identifier identifierType="URL">https://zenodo.org/record/883748</identifier> <creators> <creator> <creatorName>Royer, D. J.</creatorName> <givenName>D. J.</givenName> <familyName>Royer</familyName> </creator> <creator> <creatorName>Carr, D. J. J.</creatorName> <givenName>D. J. J.</givenName> <familyName>Carr</familyName> </creator> </creators> <titles> <title>A STING-dependent innate-sensing pathway mediates resistance to corneal HSV-1 infection via upregulation of the antiviral effector tetherin</title> </titles> <publisher>Zenodo</publisher> <publicationYear>2015</publicationYear> <dates> <date dateType="Issued">2015-12-02</date> </dates> <resourceType resourceTypeGeneral="Text">Journal article</resourceType> <alternateIdentifiers> <alternateIdentifier alternateIdentifierType="url">https://zenodo.org/record/883748</alternateIdentifier> </alternateIdentifiers> <relatedIdentifiers> <relatedIdentifier relatedIdentifierType="DOI" relationType="IsIdenticalTo">10.1038/mi.2015.124</relatedIdentifier> </relatedIdentifiers> <rightsList> <rights rightsURI="info:eu-repo/semantics/openAccess">Open Access</rights> </rightsList> <descriptions> <description descriptionType="Abstract">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.</description> </descriptions> </resource>