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To address their potential role(s) in viral infection of mucosal epithelia we currently investigate adhesion and entry mechanisms of the infectious hematopoietic necrosis virus (IHNV) using the zebrafish (Danio rerio) model system. We previously reported the recognition of IHNV envelope glycoprotein by the zebrafish galectin Drgal1-L2 and its inhibitory activity for viral adhesion to epithelial cells. Subsequently, we determined the structure of Drgal1-L2 and proposed a mechanism for Drgal1-mediated inhibition of IHNV spike fusion to the host epithelial cell. We now show that Drgal1 can also hinder viral adhesion and infection by binding to glycans on the host cell surface and epidermal mucus. We identified fibronectin, the reported IHNV receptor, as the cell surface glycoprotein recognized by Drgal1-L2. Surprisingly, IHNV also adhered in vitro to purified \u03b21integrin, and pre-exposure of either IHNV or the immobilized \u03b21integrin to Drgal1-L2 hindered IHNV adhesion. Binding of either anti-fibronectin or anti-\u03b21integrin antibodies to the cell surface partially inhibited IHNV adherence. Drgal1-L2 also hindered IHNV adhesion by binding to mucus glycans. Taken together, our results suggest complementary mechanisms by which Drgal1-L2 may protect mucosal epithelial cells against IHNV infection and tentatively identify \u03b21integrin as a novel receptor for IHNV.<\/jats:p>","DOI":"10.3390\/biom16060882","type":"journal-article","created":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T00:49:42Z","timestamp":1781743782000},"page":"882","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Proto Type Galectin Drgal1-L2 from Zebrafish Hinders Infection by the Infectious Hematopoietic Necrosis Virus by Binding to Its Glycosylated Receptors on the Epithelial Cell Surface"],"prefix":"10.3390","volume":"16","author":[{"given":"Kelsey","family":"Abernathy","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, University of Maryland School of Medicine, UMB, and Institute of Marine and Environmental Technology, Baltimore, MD 21202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6816-4859","authenticated-orcid":false,"given":"Sheng","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Maryland School of Medicine, UMB, and Institute of Marine and Environmental Technology, Baltimore, MD 21202, USA"},{"name":"State Key Laboratory for Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiguang","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Maryland School of Medicine, UMB, and Institute of Marine and Environmental Technology, Baltimore, MD 21202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin","family":"Mancini","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Maryland School of Medicine, UMB, and Institute of Marine and Environmental Technology, Baltimore, MD 21202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7335-039X","authenticated-orcid":false,"given":"Guanghui","family":"Zong","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, University of Maryland, College Park, MD 20742, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nuria","family":"Gonz\u00e1lez-Montalb\u00e1n","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Maryland School of Medicine, UMB, and Institute of Marine and Environmental Technology, Baltimore, MD 21202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lai-Xi","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, University of Maryland, College Park, MD 20742, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0642-7470","authenticated-orcid":false,"given":"Gerardo R.","family":"Vasta","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Maryland School of Medicine, UMB, and Institute of Marine and Environmental Technology, Baltimore, MD 21202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"147","DOI":"10.4310\/CIS.2021.v21.n1.a7","article-title":"Carbohydrate-Protein Interactions: Advances and Challenges","volume":"21","author":"Zhang","year":"2021","journal-title":"Commun. 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