Mechanisms of HIV-associated lymphocyte apoptosis: 2010

Abstract

The inevitable decline of CD4T cells in untreated infection with the Human immunodeficiency virus (HIV) is due in large part to apoptosis, one type of programmed cell death. There is accumulating evidence that the accelerated apoptosis of CD4T cells in HIV infection is multifactorial, with direct viral cytotoxicity, signaling events triggered by viral proteins and aberrant immune activation adding to normal immune defense mechanisms to contribute to this phenomenon. Current antiviral treatment strategies generally lead to reduced apoptosis, but this approach may come at the cost of preserving latent viral reservoirs. It is the purpose of this review to provide an update on the current understanding of the role and mechanisms of accelerated apoptosis of T cells in the immunopathogenesis of HIV infection, and to highlight potential ways in which this seemingly deleterious process could be harnessed to not just control, but treat HIV infection.

Figure 1

(a) Simplified diagram of normal CD4+ T-cell homeostasis. The peripheral CD4+ T-cell pool is maintained through a balance of thymopoiesis and activation-induced cell death. (b) Mechanisms of CD4+ T-cell death in untreated HIV infection. The peripheral CD4+ T-cell pool is depleted through decreased thymopoiesis and excessive apoptosis through multiple HIV viral-specific and non-specific mechanisms

Figure 2

This figure depicts select interactions of HIV proteins with the mitochondrial pathway of apoptosis demonstrated in in vitro studies, demonstrating the both complexity and duplicity of these pathways. Which of these potential mechanisms occurs in vivo, and the relative importance, though, is less clear