Abstract |
HIV-1 Vpr triggers NK cell-mediated lysis of infected cells by upregulating ULBP2, a ligand of the NKG2D receptor, through activation of the ATR-mediated DNA damage response. Herein, we demonstrate that Vpr augments ULBP2 expression on both infected and uninfected bystander cells during HIV-1 infection of primary CD4+ T lymphocytes. Indeed, the frequency of uninfected bystander cells expressing high levels of ULBP2 was elevated in a Vpr-dependent manner. Nevertheless, the same does not hold true for a Vpr mutant that is not packaged into virions, suggesting the involvement of virion-associated Vpr in this process. Additionally, we show that soluble Vpr has the ability to induce a DNA damage response and to augment cell-surface ULBP2 upon transducing target cells, including T cells, conditions known to promote NK cell-mediated killing. Overall, these findings suggest that Vpr could contribute to CD4+ T cell loss by rendering uninfected bystander cells susceptible to NK cell-mediated killing.
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Authors | Jonathan Richard, Tram N Q Pham, Yukihito Ishizaka, Eric A Cohen |
Journal | Virology
(Virology)
Vol. 443
Issue 2
Pg. 248-56
(Sep 01 2013)
ISSN: 1096-0341 [Electronic] United States |
PMID | 23726848
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2013 Elsevier Inc. All rights reserved. |
Chemical References |
- GPI-Linked Proteins
- Intercellular Signaling Peptides and Proteins
- ULBP2 protein, human
- vpr Gene Products, Human Immunodeficiency Virus
- vpr protein, Human immunodeficiency virus 1
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Topics |
- CD4-Positive T-Lymphocytes
(metabolism, virology)
- Cell Line
- DNA Damage
- GPI-Linked Proteins
(genetics, metabolism)
- HEK293 Cells
- HIV-1
(genetics, metabolism, pathogenicity)
- HeLa Cells
- Humans
- Intercellular Signaling Peptides and Proteins
(genetics, metabolism)
- Killer Cells, Natural
(immunology)
- Up-Regulation
- Virion
(genetics, physiology)
- vpr Gene Products, Human Immunodeficiency Virus
(genetics, metabolism)
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