title: Macrophage receptors for influenza A virus: role of the macrophage galactose-type lectin and mannose receptor in viral entry.
abstract: Although sialic acid has long been recognized as the primary receptor determinant for attachment of influenza virus to host cells, the specific receptor molecules that mediate viral entry are not known for any cell type. For the infection of murine macrophages by influenza virus, our earlier study indicated involvement of a C-type lectin, the macrophage mannose receptor (MMR), in this process. Here, we have used direct binding techniques to confirm and characterize the interaction of influenza virus with the MMR and to seek additional macrophage surface molecules that may have potential as receptors for viral entry. We identified the macrophage galactose-type lectin (MGL) as a second macrophage membrane C-type lectin that binds influenza virus and is known to be endocytic. Binding of influenza virus to MMR and MGL occurred independently of sialic acid through Ca(2+)-dependent recognition of viral glycans by the carbohydrate recognition domains of the two lectins; influenza virus also bound to the sialic acid on the MMR. Multivalent ligands of the MMR and MGL inhibited influenza virus infection of macrophages in a manner that correlated with expression of these receptors on different macrophage populations. Influenza virus strain A/PR/8/34, which is poorly glycosylated and infects macrophages poorly, was not recognized by the C-type lectin activity of either the MMR or the MGL. We conclude that lectin-mediated interactions of influenza virus with the MMR or the MGL are required for the endocytic uptake of the virus into macrophages, and these lectins can thus be considered secondary or coreceptors with sialic acid for infection of this cell type.
authors.affiliation: Department of Microbiology and Immunology, University of Melbourne, Victoria 3010, Australia. preading@unimelb.edu.au
authors.forename: Jacqueline P
authors.initials: JP
authors.lastname: Upham
authors.forename: Danielle
authors.initials: D
authors.lastname: Pickett
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Irimura
authors.forename: E Margot
authors.initials: EM
authors.lastname: Anders
authors.forename: Patrick C
authors.initials: PC
authors.lastname: Reading
mesh_terms: D000818:Animals; D001212:Asialoglycoproteins / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D002413:Cations, Divalent / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D053118:Influenza A Virus, H1N1 Subtype / Q000502:physiology*; D053122:Influenza A Virus, H3N2 Subtype / Q000502:physiology*; D037181:Lectins, C-Type / Q000502:physiology*; D008264:Macrophages / Q000821:virology*; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000502:physiology*; D008565:Membrane Proteins / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D019158:N-Acetylneuraminic Acid / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000502:physiology*; D011991:Receptors, Virus / Q000502:physiology*; D053586:Virus Internalization
chemical_list: D001212:Asialoglycoproteins; D002413:Cations, Divalent; C064720:Clec10a protein, mouse; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D008565:Membrane Proteins; D011956:Receptors, Cell Surface; D011991:Receptors, Virus; D019158:N-Acetylneuraminic Acid; D002118:Calcium