Colony-stimulating factor 1 receptor antagonists sensitize human immunodeficiency virus type 1-infected macrophages to TRAIL-mediated killing

Francesc Cunyat, Jennifer N. Rainho, Brian West, Louise Swainson, Joseph M. McCune, Mario Stevenson

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

Strategies aimed at eliminating persistent viral reservoirs from HIV-1-infected individuals have focused on CD4+ T-cell reservoirs. However, very little attention has been given to approaches that could promote elimination of tissue macrophage reservoirs. HIV-1 infection of macrophages induces phosphorylation of colony-stimulating factor 1 receptor (CSF-1R), which confers resistance to apoptotic pathways driven by tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), thereby promoting viral persistence. In this study, we assessed whether CSF-1R antagonists (PLX647, PLX3397, and PLX5622) restored apoptotic sensitivity of HIV-1-infected macrophages in vitro. PLX647, PLX3397, and PLX5622 at clinically relevant concentrations blocked the activation of CSF-1R and reduced the viability of infected macrophages, as well as the extent of viral replication. Our data show that strategies targeting monocyte colony-stimulating factor (MCSF) signaling could be used to promote elimination of HIV-1-infected myeloid cells and to contribute to the elimination of persistent viral reservoirs.

Original languageEnglish (US)
Pages (from-to)6255-6262
Number of pages8
JournalJournal of Virology
Volume90
Issue number14
DOIs
StatePublished - 2016

ASJC Scopus subject areas

  • Immunology
  • Medicine(all)
  • Virology

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