{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T12:38:19Z","timestamp":1787315899426,"version":"build-2736575974"},"reference-count":75,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T00:00:00Z","timestamp":1784505600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100001818","name":"Research to Prevent Blindness","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/100001818","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100013779","name":"Retina Research Foundation.","doi-asserted-by":"crossref","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/100013779","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Wisconsin Medical Foundation Professorship","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]},{"name":"Core Grant for Vision Research","award":["P30EY016665"],"award-info":[{"award-number":["P30EY016665"]}]},{"name":"Shared Instrumentation Grant","award":["S10OD026957"],"award-info":[{"award-number":["S10OD026957"]}]},{"name":"Shared Instrumentation Grant","award":["S10OD23526"],"award-info":[{"award-number":["S10OD23526"]}]},{"name":"University of Wisconsin Comprehensive Cancer Center Core Grant","award":["P30CA014520"],"award-info":[{"award-number":["P30CA014520"]}]},{"name":"Retina Research Foundation Professorship","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]},{"DOI":"10.13039\/100013779","name":"Retina Research Foundation","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/100013779","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>\n                    Herpes simplex virus type 1 (HSV-1) corneal infection triggers an immunopathological response and corneal neovascularization leading to vision impairment. Thrombospondin-1 (TSP-1) is a matricellular protein shown to regulate inflammatory processes and vascularization in the cornea. The purpose of this study was to determine if loss of TSP-1 alters the pathology of HSV-1 keratitis. The recombinant virus INV-2C or the low passage orolabial HSV-1 isolate, Ikey, were administered to scarified corneas of 8-week-old\n                    <jats:italic>Thbs1<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>-\/-<\/jats:italic>\n                    <\/jats:sup>\n                    and control C57BL\/6J mice. Blepharitis, corneal neovascularization, corneal clouding, weight loss, viral titers, and mortality were determined on multiple days post infection. Corneal nerve loss was evaluated on day 2 and day 7. Neutralizing antibody, T-cell responses, and infiltrating cells in the aqueous and vitreous humors were quantified. There was no significant difference between\n                    <jats:italic>Thbs1<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>-\/-<\/jats:italic>\n                    <\/jats:sup>\n                    and C57BL\/6J control mice when comparing any corneal disease outcome with either virus. Severe pan-uveitis developed in both C57BL\/6J and\n                    <jats:italic>Thbs1<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>-\/-<\/jats:italic>\n                    <\/jats:sup>\n                    mice infected with the Ikey strain of virus. There were no significant differences in antibodies to HSV or in the number of HSV-1 specific IFN-g secreting T-cells in the spleen between C57BL\/6 or TSP-1\n                    <jats:sup>-\/-<\/jats:sup>\n                    mice. The lack of TSP-1 did not affect the severity of corneal disease, immune responses to HSV-1, or sensory nerve loss suggesting either TSP-1 functions are not involved in HSV-1 pathogenesis or that other members of the TSP family can substitute for the loss of TSP-1.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0352457","type":"journal-article","created":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T17:30:12Z","timestamp":1784568612000},"page":"e0352457","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Herpes simplex virus type-1 ocular infection in thrombospondin-1 deficient C57BL\/6J mice"],"prefix":"10.1371","volume":"21","author":[{"given":"Aaron W.","family":"Kolb","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica M.","family":"Sauter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Ferguson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asha S.","family":"Jain","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2723-9217","authenticated-orcid":true,"given":"Nader K.","family":"Sheibani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine M.","family":"Sorenson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6468-514X","authenticated-orcid":true,"given":"Curtis R.","family":"Brandt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,7,20]]},"reference":[{"issue":"4","key":"pone.0352457.ref001","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1136\/sti.79.4.286","article-title":"Seroepidemiological study of herpes simplex virus types 1 and 2 in Brazil, Estonia, India, Morocco, and Sri Lanka","volume":"79","author":"FM Cowan","year":"2003","journal-title":"Sex Transm Infect"},{"issue":"4","key":"pone.0352457.ref002","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1007\/s00430-001-0102-1","article-title":"Seroprevalence of herpes simplex virus types 1 and type 2 in the Frankfurt am Main area, Germany","volume":"190","author":"HF Rabenau","year":"2002","journal-title":"Med Microbiol Immunol"},{"issue":"8","key":"pone.0352457.ref003","doi-asserted-by":"crossref","first-page":"964","DOI":"10.1001\/jama.296.8.964","article-title":"Trends in herpes simplex virus type 1 and type 2 seroprevalence in the United States","volume":"296","author":"F Xu","year":"2006","journal-title":"JAMA"},{"issue":"4","key":"pone.0352457.ref004","first-page":"726","article-title":"Seroprevalence of herpes simplex 1-2 antibodies in Brazil","volume":"44","author":"SAC Clemens","year":"2010","journal-title":"Rev Saude Publica"},{"key":"pone.0352457.ref005","first-page":"2502","article-title":"Herpes simplex viruses.","volume-title":"Fields virology","author":"B. 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