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

Wade, Jessica; Sterjovski, Jasminka; Gray, Lachlan; Roche, Ichael; Chiavaroli, Lisa; Ellett, Anne; Jakobsen, Martin R.; Cowley, Daniel; Pereira, Candida da Fonseca and Saksena, Nitin, et al. (2010) In Virology 396(2). p.246-255
Abstract
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... (More)
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. (Less)
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published
subject
keywords
Active caspase-3, Apoptosis, CCR5, CD4, HIV-1, Env
in
Virology
volume
396
issue
2
pages
246 - 255
publisher
Elsevier
external identifiers
  • wos:000273504600008
  • scopus:70749144829
ISSN
1096-0341
DOI
10.1016/j.virol.2009.10.029
language
English
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yes
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b290a16e-ba77-4c10-804b-43d7d24dd480 (old id 1547730)
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2010-02-23 13:08:11
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2018-05-29 10:20:11
@article{b290a16e-ba77-4c10-804b-43d7d24dd480,
  abstract     = {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.},
  author       = {Wade, Jessica and Sterjovski, Jasminka and Gray, Lachlan and Roche, Ichael and Chiavaroli, Lisa and Ellett, Anne and Jakobsen, Martin R. and Cowley, Daniel and Pereira, Candida da Fonseca and Saksena, Nitin and Wang, Bin and Purcell, Damian F. J. and Karlsson, Ingrid and Fenyö, Eva Maria and Churchill, Melissa and Gorry, Paul R.},
  issn         = {1096-0341},
  keyword      = {Active caspase-3,Apoptosis,CCR5,CD4,HIV-1,Env},
  language     = {eng},
  number       = {2},
  pages        = {246--255},
  publisher    = {Elsevier},
  series       = {Virology},
  title        = {Enhanced CD4+cellular apoptosis by CCR5-restricted HIV-1 envelope glycoprotein variants from patients with progressive HIV-1 infection},
  url          = {http://dx.doi.org/10.1016/j.virol.2009.10.029},
  volume       = {396},
  year         = {2010},
}