HIV-1 infection of human macrophages directly induces viperin which inhibits viral production Academic Article uri icon

abstract

  • Abstract Macrophages are key target cells for HIV-1. HIV-1BaL induced a subset of interferon-stimulated genes in monocyte-derived macrophages (MDMs), which differed from that in monocyte-derived dendritic cells and CD4 T cells, without inducing any interferons. Inhibition of type I interferon induction was mediated by HIV-1 inhibition of interferon-regulated factor (IRF3) nuclear translocation. In MDMs, viperin was the most up-regulated interferon-stimulated genes, and it significantly inhibited HIV-1 production. HIV-1 infection disrupted lipid rafts via viperin induction and redistributed viperin to CD81 compartments, the site of HIV-1 egress by budding in MDMs. Exogenous farnesol, which enhances membrane protein prenylation, reversed viperin-mediated inhibition of HIV-1 production. Mutagenesis analysis in transfected cell lines showed that the internal S-adenosyl methionine domains of viperin were essential for its antiviral activity. Thus viperin may contribute to persistent noncytopathic HIV-1 infection of macrophages and possibly to biologic differences with HIV-1–infected T cells.

authors

  • Nasr, N
  • Maddocks, S
  • Turville, SG
  • Harman, AN
  • Woolger, N
  • Helbig, KJ
  • Wilkinson, J
  • Bye, CR
  • Wright, TK
  • Rambukwelle, D
  • Donaghy, H
  • Beard, MR
  • Cunningham, AL

publication date

  • 2012

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