title: Differential N-linked glycosylation of human immunodeficiency virus and Ebola virus envelope glycoproteins modulates interactions with DC-SIGN and DC-SIGNR.
abstract: The C-type lectins DC-SIGN and DC-SIGNR [collectively referred to as DC-SIGN(R)] bind and transmit human immunodeficiency virus (HIV) and simian immunodeficiency virus to T cells via the viral envelope glycoprotein (Env). Other viruses containing heavily glycosylated glycoproteins (GPs) fail to interact with DC-SIGN(R), suggesting some degree of specificity in this interaction. We show here that DC-SIGN(R) selectively interact with HIV Env and Ebola virus GPs containing more high-mannose than complex carbohydrate structures. Modulation of N-glycans on Env or GP through production of viruses in different primary cells or in the presence of the mannosidase I inhibitor deoxymannojirimycin dramatically affected DC-SIGN(R) infectivity enhancement. Further, murine leukemia virus, which typically does not interact efficiently with DC-SIGN(R), could do so when produced in the presence of deoxymannojirimycin. We predict that other viruses containing GPs with a large proportion of high-mannose N-glycans will efficiently interact with DC-SIGN(R), whereas those with solely complex N-glycans will not. Thus, the virus-producing cell type is an important factor in dictating both N-glycan status and virus interactions with DC-SIGN(R), which may impact virus tropism and transmissibility in vivo.
authors.affiliation: Hematology-Oncology Division, Department of Medicine, University of Pennsylvania, Philadelphia 19104, USA.
authors.forename: George
authors.initials: G
authors.lastname: Lin
authors.forename: Graham
authors.initials: G
authors.lastname: Simmons
authors.forename: Stefan
authors.initials: S
authors.lastname: Pöhlmann
authors.forename: Frédéric
authors.initials: F
authors.lastname: Baribaud
authors.forename: Houping
authors.initials: H
authors.lastname: Ni
authors.forename: George J
authors.initials: GJ
authors.lastname: Leslie
authors.forename: Beth S
authors.initials: BS
authors.lastname: Haggarty
authors.forename: Paul
authors.initials: P
authors.lastname: Bates
authors.forename: Drew
authors.initials: D
authors.lastname: Weissman
authors.forename: James A
authors.initials: JA
authors.lastname: Hoxie
authors.forename: Robert W
authors.initials: RW
authors.lastname: Doms
mesh_terms: D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002460:Cell Line; D029043:Ebolavirus / Q000378:metabolism*; D006031:Glycosylation; D006678:HIV / Q000378:metabolism*; D006801:Humans; D037181:Lectins, C-Type / Q000378:metabolism*; D011134:Polysaccharides / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism*; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000378:metabolism*; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
chemical_list: D015815:Cell Adhesion Molecules; D037181:Lectins, C-Type; D011134:Polysaccharides; D011956:Receptors, Cell Surface; D014759:Viral Envelope Proteins; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C433029:CLEC4M protein, human