title: Endocytic function is critical for influenza A virus infection via DC-SIGN and L-SIGN.
abstract: The ubiquitous presence of cell-surface sialic acid (SIA) has complicated efforts to identify specific transmembrane glycoproteins that function as bone fide entry receptors for influenza A virus (IAV) infection. The C-type lectin receptors (CLRs) DC-SIGN (CD209) and L-SIGN (CD209L) enhance IAV infection however it is not known if they act as attachment factors, passing virions to other unknown receptors for virus entry, or as authentic entry receptors for CLR-mediated virus uptake and infection. Sialic acid-deficient Lec2 Chinese Hamster Ovary (CHO) cell lines were resistant to IAV infection whereas expression of DC-SIGN/L-SIGN restored susceptibility of Lec2 cells to pH- and dynamin-dependent infection. Moreover, Lec2 cells expressing endocytosis-defective DC-SIGN/L-SIGN retained capacity to bind IAV but showed reduced susceptibility to infection. These studies confirm that DC-SIGN and L-SIGN are authentic endocytic receptors for IAV entry and infection.
authors.affiliation: Department of Microbiology and Immunology, University of Melbourne, at The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria 3000, Australia.
authors.forename: Leah
authors.initials: L
authors.lastname: Gillespie
authors.affiliation: Department of Microbiology and Immunology, University of Melbourne, at The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria 3000, Australia.
authors.forename: Paula
authors.initials: P
authors.lastname: Roosendahl
authors.affiliation: Department of Microbiology and Immunology, University of Melbourne, at The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria 3000, Australia.
authors.forename: Wy Ching
authors.initials: WC
authors.lastname: Ng
authors.affiliation: Department of Microbiology and Immunology, University of Melbourne, at The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria 3000, Australia.
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Brooks
authors.affiliation: Department of Microbiology and Immunology, University of Melbourne, at The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria 3000, Australia.|WHO Collaborating Centre for Reference and Research on Influenza, Victorian Infectious Diseases Reference Laboratory, at The Peter Doherty Institute for Infection and Immunity, 792 Elizabeth St, Victoria 3000, Australia.
authors.forename: Patrick C
authors.initials: PC
authors.lastname: Reading
authors.affiliation: Department of Microbiology and Immunology, University of Melbourne, at The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria 3000, Australia.
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Londrigan
mesh_terms: D000818:Animals; D016466:CHO Cells; D015815:Cell Adhesion Molecules / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D003412:Cricetulus; D004285:Dogs; D034281:Dynamins / Q000378:metabolism; D004705:Endocytosis; D015870:Gene Expression; D006863:Hydrogen-Ion Concentration; D009980:Influenza A virus / Q000502:physiology*; D037181:Lectins, C-Type / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D019158:N-Acetylneuraminic Acid / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011991:Receptors, Virus / Q000378:metabolism*; D053585:Virus Attachment; D053586:Virus Internalization; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
chemical_list: D015815:Cell Adhesion Molecules; D034281:Dynamins; D037181:Lectins, C-Type; D019158:N-Acetylneuraminic Acid; D011956:Receptors, Cell Surface; D011991:Receptors, Virus; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin