title: The macrophage galactose-type lectin can function as an attachment and entry receptor for influenza virus.
abstract: Specific protein receptors that mediate internalization and entry of influenza A virus (IAV) have not been identified for any cell type. Sialic acid (SIA), the primary attachment factor for IAV hemagglutinin, is expressed by numerous cell surface glycoproteins and glycolipids, confounding efforts to identify specific receptors involved in virus infection. Lec1 Chinese hamster ovary (CHO) epithelial cells express cell surface SIA and bind IAV yet are largely resistant to infection. Here, we demonstrate that expression of the murine macrophage galactose-type lectin 1 (MGL1) by Lec1 cells enhanced Ca(2+)-dependent IAV binding and restored permissivity to infection. Lec1 cells expressing MGL1 were infected in the presence or absence of cell surface SIA, indicating that MGL1 can act as a primary receptor or as a coreceptor with SIA. Lec1 cells expressing endocytosis-deficient MGL1 mediated Ca(2+)-dependent IAV binding but were less sensitive to IAV infection, indicating that direct internalization via MGL1 can result in cellular infection. Together, these studies identify MGL1 as a cell surface glycoprotein that can act as an authentic receptor for both attachment and infectious entry of IAV.
authors.affiliation: Department of Microbiology and Immunology, University of Melbourne, Victoria, Australia.
authors.forename: Wy Ching
authors.initials: WC
authors.lastname: Ng
authors.forename: Stella
authors.initials: S
authors.lastname: Liong
authors.forename: Michelle D
authors.initials: MD
authors.lastname: Tate
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Irimura
authors.forename: Kaori
authors.initials: K
authors.lastname: Denda-Nagai
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Brooks
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Londrigan
authors.forename: Patrick C
authors.initials: PC
authors.lastname: Reading
mesh_terms: D000818:Animals; D001212:Asialoglycoproteins / Q000235:genetics / Q000378:metabolism*; D016466:CHO Cells; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D006801:Humans; D009980:Influenza A virus / Q000235:genetics / Q000502:physiology*; D007251:Influenza, Human / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D037181:Lectins, C-Type / Q000235:genetics / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism / Q000821:virology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D011991:Receptors, Virus / Q000235:genetics / Q000378:metabolism*; D053585:Virus Attachment; D053586:Virus Internalization
chemical_list: D001212:Asialoglycoproteins; C064720:Clec10a protein, mouse; D037181:Lectins, C-Type; D008565:Membrane Proteins; D011991:Receptors, Virus; D002118:Calcium