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Viral protein R upregulates expression of ULBP2 on uninfected bystander cells during HIV-1 infection of primary CD4+ T lymphocytes.

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.
AuthorsJonathan Richard, Tram N Q Pham, Yukihito Ishizaka, Eric A Cohen
JournalVirology (Virology) Vol. 443 Issue 2 Pg. 248-56 (Sep 01 2013) ISSN: 1096-0341 [Electronic] United States
PMID23726848 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 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
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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