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

Summary, in English

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.

• Författare: 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
• Avdelning/ar: Avdelningen för medicinsk mikrobiologi
• Publiceringsår: 2010
• Språk: Engelska
• Sidor: 246-255
• Publikation/Tidskrift/Serie: Virology
• Volym: 396
• Issue: 2
• Länkar: http://dx.doi.org/10.1016/j.virol.2009.10.029
• Dokumenttyp: Artikel i tidskrift
• Förlag: Elsevier
• Ämne: Microbiology in the medical area
• Nyckelord: Active caspase-3; Apoptosis; CCR5; CD4; HIV-1; Env
• Status: Published
• ISBN/ISSN/Övrigt: ISSN: 1096-0341