Enhanced CD4+cellular apoptosis by CCR5-restricted HIV-1 envelope glycoprotein variants from patients with progressive HIV-1 infection

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CCR5-using (R5) human immunodeficiency virus type 1 (HIV-1) strains cause CD4+ T-cell loss in most infected individuals, but mechanisms underlying cytopathicity of R5 viruses are poorly understood. We investigated mechanisms contributing to R5 envelope glycoprotein (Env)-mediated cellular apoptosis by constructing a panel of retroviral vectors engineered to co-express GFP and R5 Envs derived from two HIV-1 infected subjects spanning asymptomatic (Early, E-R5 Envs) to late stages of infection (Late, L-R5 Envs). The L-R5 Envs induced significantly more cellular apoptosis than E-R5 Envs, but only in Env-expressing (GFP-positive) cells, and only in cells where CD4 and CCR5 levels were limiting. Studies with fusion-defective Env mutants showed induction of apoptosis required membrane-fusing events. Our results provide evidence for an intracellular mechanism of R5 Env-induced apoptosis of CD4+ cells that requires membrane fusion. Furthermore, they contribute to a better understanding of mechanisms involved in CD4+ T-cell loss in subjects experiencing progressive R5 HIV-1 infection. (C) 2009 Elsevier Inc. All rights reserved.


  • Jessica Wade
  • Jasminka Sterjovski
  • Lachlan Gray
  • Ichael Roche
  • Lisa Chiavaroli
  • Anne Ellett
  • Martin R. Jakobsen
  • Daniel Cowley
  • Candida da Fonseca Pereira
  • Nitin Saksena
  • Bin Wang
  • Damian F. J. Purcell
  • Ingrid Karlsson
  • Eva Maria Fenyö
  • Melissa Churchill
  • Paul R. Gorry
Enheter & grupper

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Mikrobiologi inom det medicinska området


Sidor (från-till)246-255
Utgåva nummer2
StatusPublished - 2010
Peer review utfördJa