The reduction in apoptosis caused by short-term exposure of CEM x174 cells infected with SIVmac239 to morphine was investigated. Eeffects of morphine on the viability of normal and infected CEM x174 cells were determined by MTS assay. Apoptosis induced by SIVmac239 and the effects of morphine were analyzed by flow cytometry. cAMP levels, PKA activity, and the resulting histone H3 phosphorylation levels were measured. The results show a pronounced decrease in numbers of infected SIVmac239 cells compared to controls. Morphine elevated cell viability in the infected groups. Annexin V binding assays showed that 1 microM l(-1) morphine increased the percentage of viable cells and decreased apoptotic cells. Morphine also downregulated cAMP and PKA activity in both groups, but more markedly in the infected group. Histone H3 phosphorylation was elevated after virus infection and decreased in the presence of morphine. The results indicate that the cAMP-PKA signal transduction cascade is involved in morphine regulation of early SIVmac239-induced apoptosis.