Non-Infectious Cxcr4-Tropic HIV Induces T-Cell Death and Possibly AIDS

A gradual decline in CD4 T-Cells is the main hallmark of HIV infection. At the "T-Cell inflection point", there is an accelerated CD4 T-Cell decline and the onset of CD8 T-Cell decline, leading up to Aquired Immune Deficiency Syndrome (AIDS). Strains of HIV that can bind the CXCR4 co-receptor emerge prior to this, suggesting that they contribute to immune failure by inducing death in naive, CXCR4-bearing T-Cells. Naive T-Cells are critical for replenishing the immune system after any kind of T-Cell loss. Additionally, the vast majority of HIV virions circulating during infection are defective and non- infectious. Their effects on immune cells are not clearly understood. In this study, primary peripheral blood T-cells were exposed to inactivated, non-infectious, HIV-1 virions. The study shows that when T-cell subsets were purified and isolated from each other, CXCR4- tropic virions induce a significantly greater decline in the number of naive, CD4 T-cells as opposed to the CCR5-tropic strains which initiate HIV infection (P=0.013). The emergence of CXCR4-utilizing HIV virions later on during infection may therefore contribute to the development of AIDS.