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

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

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskriftPeer review

Sammanfattning

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.
Originalspråkengelska
Sidor (från-till)246-255
TidskriftVirology
Volym396
Nummer2
DOI
StatusPublished - 2010

Ämnesklassifikation (UKÄ)

  • Mikrobiologi inom det medicinska området

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