HIV-1 Env Glycoprotein Phenotype along with Immune Activation Determines CD4 T Cell Loss in HIV Patients

The Journal of Immunology : Official Journal of the American Association of Immunologists
Anjali JoshiHimanshu Garg

Abstract

The mechanism behind the selective depletion of CD4(+) cells in HIV infections remains undetermined. Although HIV selectively infects CD4(+) cells, the relatively few infected cells in vivo cannot account for the extent of CD4(+) T cell depletion, suggesting indirect or bystander mechanisms. The role of virus replication, Env glycoprotein phenotype, and immune activation (IA) in this bystander phenomenon remains controversial. Using samples derived from HIV-infected patients, we demonstrate that, although IA in both CD4(+) and CD8(+) subsets correlates with CD4 decline, apoptosis in CD4(+) and not CD8(+) cells is associated with disease progression. Because HIV-1 Env glycoprotein has been implicated in bystander apoptosis, we cloned full-length Envs from plasma of viremic patients and tested their apoptosis-inducing potential (AIP). Interestingly, AIP of HIV-1 Env glycoproteins were found to correlate inversely with CD4:CD8 ratios, suggesting a role of Env phenotype in disease progression. In vitro mitogenic stimulation of PBMCs resulted in upregulation of IA markers but failed to alter the CD4:CD8 ratio. However, coculture of normal PBMCs with Env-expressing cells resulted in selective CD4 loss that was significantly enhanced ...Continue Reading

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Citations

Aug 23, 2017·Viruses·Himanshu Garg, Anjali Joshi
Jul 1, 2016·Journal of Virology·Xavier Dagenais-LussierJulien van Grevenynghe
Oct 30, 2019·AIDS Research and Human Retroviruses·Ana C PaimNathan W Cummins
May 27, 2020·Scientific Reports·Adam Penn-NicholsonUNKNOWN CAPRISA IMPRESS team
Aug 23, 2019·The Journal of Infectious Diseases·Xi ChenYongjun Jiang
May 18, 2021·Frontiers in Microbiology·Romina Cabrera-RodríguezAgustín Valenzuela-Fernández

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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