Evolution of SIV envelope in morphine-dependent rhesus macaques with rapid disease progression.

Three morphine-dependent rhesus macaques that developed accelerated AIDS after virus inoculation, along with three control macaques, were followed for evolution of the SIV/17E-Fr envelope. Viral RNA was isolated from plasma samples collected at weeks 6, 12, and 20 postinfection. A 482-nucleotide fragment in the viral env was amplified and cloned into a pCR2.1-TOPO vector. Between 5 and 10 clones were sequenced at each time point from individual monkeys. The sequence analysis showed more mutations in the control animals compared to those seen in the morphine-dependent animals. The virus at different points did not separate completely in phylogenetic analysis. However, the phylogenetic clustering was more apparent in the control animals. Viral diversity and divergence were significantly higher in the control animals. The control animals lost N-glycosylation sites more rapidly. These results suggest that morphine dependence diminished virus evolution in SHIV/SIV-infected rhesus macaques and there was an inverse correlation between virus evolution and onset of clinical disease.