Variable region 4 of SIV envelope correlates with rapid disease progression in morphine-exposed macaques infected with SIV/SHIV.

We analyzed the association between the evolution of the V3-V5 regions of env and disease progression in our SIV/SHIV macaque model of morphine dependence and AIDS. Previous studies revealed two distinct disease patterns--fast progression and normal progression. To determine the effect of the two distinct patterns of disease in the evolution of SIV/17E-Fr envelope, we analyzed env sequences from three morphine-dependent macaques that developed accelerated AIDS and three morphine-dependent macaques that developed AIDS at a slower rate and compared them to control macaques. Morphine-dependent animals exhibited a higher percentage of diversity in both plasma and CSF compartments within V4 when compared to controls. Divergence from the inoculum was significantly greater in the morphine group as compared to controls in CSF but not in plasma. We also found a direct correlation in V4 evolution and rapid disease progression. These results indicate that morphine dependence plays a role in the pathogenesis of SIV/SHIV infection and env evolution.