title: Viral capsid is a pathogen-associated molecular pattern in adenovirus keratitis.
abstract: Human adenovirus (HAdV) infection of the human eye, in particular serotypes 8, 19 and 37, induces the formation of corneal subepithelial leukocytic infiltrates. Using a unique mouse model of adenovirus keratitis, we studied the role of various virus-associated molecular patterns in subsequent innate immune responses of resident corneal cells to HAdV-37 infection. We found that neither viral DNA, viral gene expression, or viral replication was necessary for the development of keratitis. In contrast, empty viral capsid induced keratitis and a chemokine profile similar to intact virus. Transfected viral DNA did not induce leukocyte infiltration despite CCL2 expression similar to levels in virus infected corneas. Mice without toll-like receptor 9 (Tlr9) signaling developed clinical keratitis upon HAdV-37 infection similar to wild type mice, although the absolute numbers of activated monocytes in the cornea were less in Tlr9(-/-) mice. Virus induced leukocytic infiltrates and chemokine expression in mouse cornea could be blocked by treatment with a peptide containing arginine glycine aspartic acid (RGD). These results demonstrate that adenovirus infection of the cornea induces chemokine expression and subsequent infiltration by leukocytes principally through RGD contact between viral capsid and the host cell, possibly through direct interaction between the viral capsid penton base and host cell integrins.
authors.affiliation: University of Oklahoma Health Sciences Center, Department of Ophthalmology, Oklahoma City, Oklahoma, United States of America.
authors.forename: Ashish V
authors.initials: AV
authors.lastname: Chintakuntlawar
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Zhou
authors.forename: Jaya
authors.initials: J
authors.lastname: Rajaiya
authors.forename: James
authors.initials: J
authors.lastname: Chodosh
mesh_terms: D000256:Adenoviridae / Q000235:genetics / Q000276:immunology; D000257:Adenoviridae Infections / Q000235:genetics / Q000276:immunology*; D000818:Animals; D002213:Capsid / Q000276:immunology*; D036022:Capsid Proteins / Q000276:immunology*; D002469:Cell Separation; D018932:Chemokine CCL2 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression; D005814:Genes, Viral; D006801:Humans; D007150:Immunohistochemistry; D007634:Keratitis / Q000276:immunology / Q000821:virology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D009842:Oligopeptides / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051217:Toll-Like Receptor 9 / Q000235:genetics / Q000276:immunology
chemical_list: D036022:Capsid Proteins; D018932:Chemokine CCL2; D009842:Oligopeptides; D051217:Toll-Like Receptor 9; C047981:arginyl-glycyl-aspartic acid