title: HIV-1 N-glycan composition governs a balance between dendritic cell-mediated viral transmission and antigen presentation.
abstract: The natural function of dendritic cells (DCs) is to capture and degrade pathogens for Ag presentation. However, HIV-1 can evade viral degradation by DCs and hijack DCs for migration to susceptible CD4(+) T lymphocytes. It is unknown what factors decide whether a virus is degraded or transmitted to T cells. The interaction of DCs with HIV-1 involves C-type lectin receptors, such as DC-specific ICAM-3-grabbing nonintegrin, which bind to the envelope glycoprotein complex (Env), which is decorated heavily with N-linked glycans. We hypothesized that the saccharide composition of the Env N-glycans is involved in avoiding viral degradation and Ag presentation, as well as preserving infectious virus for the transmission to target cells. Therefore, we studied the fate of normally glycosylated virus versus oligomannose-enriched virus in DCs. Changing the heterogeneous N-linked glycan composition of Env to uniform oligomannose N-glycans increased the affinity of HIV-1 for DC-specific ICAM-3-grabbing nonintegrin and enhanced the capture of HIV-1 by immature DCs; however, it decreased the subsequent transmission to target cells. Oligomannose-enriched HIV-1 was directed more efficiently into the endocytic pathway, resulting in enhanced viral degradation and reduced virus transfer to target cells. Furthermore, Env containing exclusively oligomannose N-glycans was presented to Env-specific CD4(+) T cells more efficiently. Taken together, our results showed that the HIV-1 N-glycan composition plays a crucial role in the balance between DC-mediated Ag degradation and presentation and DC-mediated virus transmission to target cells. This finding may have implications for the early events in HIV-1 transmission and the induction of antiviral immune responses.
authors.affiliation: Laboratory of Experimental Virology, Department of Medical Microbiology, Center for Infection and Immunity Amsterdam, Academic Medical Center of the University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.
authors.forename: Thijs
authors.initials: T
authors.lastname: van Montfort
authors.forename: Dirk
authors.initials: D
authors.lastname: Eggink
authors.forename: Maikel
authors.initials: M
authors.lastname: Boot
authors.forename: Michael
authors.initials: M
authors.lastname: Tuen
authors.forename: Catarina E
authors.initials: CE
authors.lastname: Hioe
authors.forename: Ben
authors.initials: B
authors.lastname: Berkhout
authors.forename: Rogier W
authors.initials: RW
authors.lastname: Sanders
mesh_terms: D017951:Antigen Presentation / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D057809:HEK293 Cells; D015699:HIV Envelope Protein gp120 / Q000276:immunology / Q000378:metabolism; D015658:HIV Infections / Q000276:immunology* / Q000378:metabolism / Q000635:transmission*; D015497:HIV-1 / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D037181:Lectins, C-Type / Q000378:metabolism; D009844:Oligosaccharides / Q000378:metabolism*; D011134:Polysaccharides / Q000276:immunology / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism; D014771:Virion / Q000276:immunology / Q000378:metabolism; D053585:Virus Attachment; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
chemical_list: D015815:Cell Adhesion Molecules; D015699:HIV Envelope Protein gp120; D037181:Lectins, C-Type; D009844:Oligosaccharides; D011134:Polysaccharides; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C028569:oligomannoside