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.
Footnotes
This work was supported by AIDS Fund (Amsterdam) Grants 2005021 (to B.B.) and 2008013 (to R.W.S.). R.W.S. is a recipient of Veni and Vidi fellowships from The Netherlands Organization for Scientific Research and a Mathilde Krim research fellowship from the American Foundation for AIDS Research.
Abbreviations used in this article:
- CLR
- C-type lectin receptor
- DC
- dendritic cell
- DCIR
- dendritic cell immunoreceptor
- DC-SIGN
- dendritic cell-specific ICAM-3–grabbing nonintegrin
- EGFP
- enhanced GFP
- Env
- envelope glycoprotein complex
- ER
- endoplasmic reticulum
- GnTI
- GlcNAc transferase I enzyme
- iDC
- immature dendritic cell
- PEI
- polyethylenimine
- Raji–DC-SIGN cell
- Raji cell expressing dendritic cell-specific ICAM-3–grabbing nonintegrin
- TSM
- tris saline magnesium buffer
- wt
- wild-type.
- Received June 24, 2011.
- Accepted August 26, 2011.
- Copyright © 2011 by The American Association of Immunologists, Inc.