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| Content Provider | PubMed Central |
|---|---|
| Author | Puryear, Wendy Blay Akiyama, Hisashi Geer, Suzanne D. Ramirez, Nora P. Yu, Xinwei Reinhard, Björn M. Gummuluru, Suryaram |
| Editor | Aiken, Christopher |
| Copyright Year | 2013 |
| Abstract | Human immunodeficiency virus type 1 (HIV-1) interactions with myeloid dendritic cells (DCs) can result in virus dissemination to CD4+ T cells via a trans infection pathway dependent on virion incorporation of the host cell derived glycosphingolipid (GSL), GM3. The mechanism of DC-mediated trans infection is extremely efficacious and can result in infection of multiple CD4+ T cells as these cells make exploratory contacts on the DC surface. While it has long been appreciated that activation of DCs with ligands that induce type I IFN signaling pathway dramatically enhances DC-mediated T cell trans infection, the mechanism by which this occurs has remained unclear until now. Here, we demonstrate that the type I IFN-inducible Siglec-1, CD169, is the DC receptor that captures HIV in a GM3-dependent manner. Selective downregulation of CD169 expression, neutralizing CD169 function, or depletion of GSLs from virions, abrogated DC-mediated HIV-1 capture and trans infection, while exogenous expression of CD169 in receptor-naïve cells rescued GSL-dependent capture and trans infection. HIV-1 particles co-localized with CD169 on DC surface immediately following capture and subsequently within non-lysosomal compartments that redistributed to the DC – T cell infectious synapses upon initiation of T cell contact. Together, these findings describe a novel mechanism of pathogen parasitization of host encoded cellular recognition machinery (GM3 – CD169 interaction) for DC-dependent HIV dissemination. |
| Related Links | http://dx.doi.org/10.1371/journal.ppat.1003291 |
| Starting Page | 1003291 |
| File Format | |
| ISSN | 15537374 |
| e-ISSN | 15537374 |
| Journal | PLoS Pathogens |
| Issue Number | 4 |
| Volume Number | 9 |
| Language | English |
| Publisher | Public Library of Science |
| Publisher Date | 2013-04-01 |
| Access Restriction | Open |
| Rights Holder | Public Library of Science |
| Subject Keyword | Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Genetics Virology Molecular Biology Parasitology Immunology Microbiology |
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