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

Virology
Jessica WadePaul R Gorry

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.

References

Dec 1, 1995·Nature Medicine·S GlushakovaJ Zimmerberg
Jul 24, 1998·Trends in Microbiology·A M de Roda Husman, H Schuitemaker
Feb 19, 2005·Cell Death and Differentiation·J-L PerfettiniG Kroemer
Nov 1, 2006·Current HIV Research·Jasminka SterjovskiPaul R Gorry
May 27, 2008·Cellular and Molecular Life Sciences : CMLS·H Garg, R Blumenthal
Jul 22, 2009·AIDS Research and Human Retroviruses·Himanshu GargRobert Blumenthal

❮ Previous
Next ❯

Citations

Jun 15, 2011·AIDS Research and Human Retroviruses·Andrew D ReddUNKNOWN Rakai Health Sciences Program
Dec 4, 2012·Viruses·Himanshu GargAnjali Joshi
Dec 29, 2010·Current HIV/AIDS Reports·Paul R Gorry, Petronela Ancuta
Nov 23, 2013·The Journal of Biological Chemistry·Anjali JoshiHimanshu Garg
Jan 15, 2016·The Journal of Immunology : Official Journal of the American Association of Immunologists·Anjali JoshiHimanshu Garg

❮ Previous
Next ❯

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Aminoglycosides

Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside. Discover the latest research on aminoglycoside here.

Aminoglycosides (ASM)

Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside. Discover the latest research on aminoglycoside here.