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EKC is mainly caused by six types of human adenovirus (HAdV): HAdV-8, -19, -37, -53, -54, and -56. Of these, HAdV-8, -19, and -37 use sialic acid-containing glycans as cellular receptors. \u03b1V\u03b23, \u03b1V\u03b25, and a few additional integrins facilitate entry and endosomal release of other HAdVs. With the exception of a few biochemical analyses indicating that HAdV-37 can interact physically with \u03b1V\u03b25, little is known about the integrins used by EKC-causing HAdVs. Here, we investigated the overall integrin expression on human corneal cells and found expression of \u03b12, \u03b13, \u03b16, \u03b1V, \u03b21, and \u03b24 subunits in human corneal<jats:italic>in situ<\/jats:italic>epithelium and\/or in a human corneal epithelial (HCE) cell line but no or less accessible expression of \u03b14, \u03b15, \u03b23, or \u03b25. We also identified the integrins used by HAdV-37 through a series of binding and infection competition experiments and different biochemical approaches. Together, our data suggest that HAdV-37 uses \u03b1V\u03b21 and \u03b13\u03b21 integrins for infection of human corneal epithelial cells. Furthermore, to confirm the relevance of these integrins in the HAdV-37 life cycle, we developed a corneal multilayer tissue system and found that HAdV-37 infection correlated well with the patterns of \u03b1V, \u03b13, and \u03b21 integrin expression. These results provide further insight into the tropism and pathogenesis of EKC-causing HAdVs and may be of importance for future development of new antiviral drugs.<\/jats:p><jats:p><jats:bold>IMPORTANCE<\/jats:bold>Keratitis is a hallmark of EKC, which is caused by six HAdV types (HAdV-8, -19, -37, -53, -54, and -56). HAdV-37 and some other HAdV types interact with integrin \u03b1V\u03b25 in order to enter nonocular human cells. In this study, we found that \u03b1V\u03b25 is not expressed on human corneal epithelial cells, thus proposing other host factors mediate corneal infection. Here, we first characterized integrin expression patterns on corneal tissue and corneal cells. Among the integrins identified, competition binding and infection experiments and biochemical assays pointed out \u03b1V\u03b21 and \u03b13\u03b21 to be of importance for HAdV-37 infection of corneal tissue. In the absence of a good animal model for EKC-causing HAdVs, we also developed an<jats:italic>in vitro<\/jats:italic>system with multilayer HCE cells and confirmed the relevance of the suggested integrins during HAdV-37 infection.<\/jats:p>","DOI":"10.1128\/jvi.02019-16","type":"journal-article","created":{"date-parts":[[2017,1,9]],"date-time":"2017-01-09T14:32:33Z","timestamp":1483972353000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":36,"title":["Human Adenovirus Type 37 Uses \u03b1<sub>V<\/sub>\u03b2<sub>1<\/sub>and \u03b1<sub>3<\/sub>\u03b2<sub>1<\/sub>Integrins for Infection of Human Corneal Cells"],"prefix":"10.1128","volume":"91","author":[{"given":"Rickard J.","family":"Storm","sequence":"first","affiliation":[{"name":"Division of Virology, Department of Clinical Microbiology, Ume\u00e5 University, Ume\u00e5, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B. David","family":"Persson","sequence":"additional","affiliation":[{"name":"Division of Virology, Department of Clinical Microbiology, Ume\u00e5 University, Ume\u00e5, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars Nyg\u00e5rd","family":"Skalman","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry and Biophysics, Ume\u00e5 University, Ume\u00e5, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Fr\u00e4ngsmyr","sequence":"additional","affiliation":[{"name":"Division of Virology, Department of Clinical Microbiology, Ume\u00e5 University, Ume\u00e5, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mona","family":"Lindstr\u00f6m","sequence":"additional","affiliation":[{"name":"Department of Integrative Medical Biology, Ume\u00e5 University, Ume\u00e5, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Greg","family":"Rankin","sequence":"additional","affiliation":[{"name":"Department of Public Health and Clinical Medicine, Norrland University Hospital (NUS), Ume\u00e5 University, Ume\u00e5, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Lundmark","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry and Biophysics, Ume\u00e5 University, Ume\u00e5, Sweden"},{"name":"Department of Integrative Medical Biology, Ume\u00e5 University, Ume\u00e5, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatima Pedrosa","family":"Domell\u00f6f","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, Ophthalmology, Ume\u00e5 University, Ume\u00e5, Sweden"},{"name":"Department of Integrative Medical Biology, Ume\u00e5 University, Ume\u00e5, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niklas","family":"Arnberg","sequence":"additional","affiliation":[{"name":"Division of Virology, Department of Clinical Microbiology, Ume\u00e5 University, Ume\u00e5, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","first-page":"2395","volume-title":"Fields virology","author":"Wold WSM","year":"2007","unstructured":"Wold WSM Horwitz MS . 2007. 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