CD155 on HIV-Infected Cells Is Not Modulated by HIV-1 Vpu and Nef but Synergizes with NKG2D Ligands to Trigger NK Cell Lysis of Autologous Primary HIV-Infected Cells

Zachary B. Davis, Bharatwaj Sowrirajan, Andrew Cogswell, Jeffery P. Ward, Vicente Planelles, Edward Barker

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Activation of primary CD4+ T cells induces the CD155, but not the CD112 ligands for the natural killer (NK) cell activation receptor (aNKR) CD226 [DNAX accessory molecule-1 (DNAM-1)]. We hypothesize that HIV productively infects activated CD4+ T cells and makes itself vulnerable to NK cell-mediated lysis when CD155 on infected T cells engages DNAM-1. The primary objective of this study is to determine whether CD155 alone or together with NKG2D ligands triggers autologous NK cell lysis of HIV-infected T cells and whether HIV modulates CD155. To determine whether HIV modulates this activation ligand, we infected "activated" CD4+ T cells with HIV in the absence or presence of Nef and/or Vpu and determined by flow cytometry whether they modulated CD155. To determine if CD155 alone, or together with NKG2D ligands, triggered NK cell lysis of autologous HIV-infected T cells, we treated purified NK cells with DNAM-1 and/or NKG2D blocking antibodies before the addition of purified autologous HIV-infected cells in cytolytic assays. Finally, we determined whether DNAM-1 works together with NKG2D as an NK cell coactivation receptor (caNKR) or whether they work independently as aNKRs to induce an NK cell lytic response. We demonstrate that HIV and specifically Nef and/or Vpu do not modulate CD155 on infected primary T cells; and both CD155 and NKG2D ligands synergize as aNKRs to trigger NK cell lysis of the infected cell.

Original languageEnglish (US)
Pages (from-to)93-100
Number of pages8
JournalAIDS Research and Human Retroviruses
Volume33
Issue number2
DOIs
StatePublished - Feb 1 2017
Externally publishedYes

Bibliographical note

Publisher Copyright:
© Copyright 2017, Mary Ann Liebert, Inc. 2017.

Keywords

  • Cytotoxic
  • HIV
  • Natural killer cells
  • Nef
  • Vpu

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