HIV-1 N-glycan composition governs a balance between dendritic cell-mediated viral transmission and antigen presentation

Thijs Van Montfort, Dirk Eggink, Maikel Boot, Michael Tuen, Catarina E. Hioe, Ben Berkhout, Rogier W. Sanders

Research output: Contribution to journalArticlepeer-review

41 Scopus citations

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 non-integrin 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. The Journal of Immunology, 2011, 187: 4676-4685.

Original languageEnglish
Pages (from-to)4676-4685
Number of pages10
JournalJournal of Immunology
Volume187
Issue number9
DOIs
StatePublished - 1 Nov 2011
Externally publishedYes

Fingerprint

Dive into the research topics of 'HIV-1 N-glycan composition governs a balance between dendritic cell-mediated viral transmission and antigen presentation'. Together they form a unique fingerprint.

Cite this