Sr. Vlahakis et al., Chemokine-receptor activation by env determines the mechanism of death in HIV-infected and uninfected T lymphocytes, J CLIN INV, 107(2), 2001, pp. 207-215
There is considerable confusion concerning the mechanism of lymphocyte deat
h during HIV infection. During the course of HIV infection, M-tropic viruse
s (R5) that use CCR5 chemokine coreceptors frequently evolve to T-tropic vi
ruses (X4) that use CXCR4 receptors. In this study we show that activation
of the CD4 or CCR5 receptor by R5 HIVenv causes a caspase 8-dependent death
of both uninfected and infected CD4 T cells. In contrast, CXCR4 activation
by X4 HIVenv induces a caspase-independent death of both uninfected CD4 an
d CD8 T cells and infected CD4 cells. These results suggest that activation
of the chemokine receptor by HIVenv determines the mechanism of death for
both infected and uninfected T lymphocytes.