The U3 promoter region of the acutely lethal simian immunodeficiency virus clone smmPBjl.9 confers related biological activity on the apathogenic clone agm3mc (acute disease/apathogenicity/virulence/genetic determinants of pathogenicity/replication competence in nonstimulated peripheral blood mononu

Infection with the acutely pathogenic molec- ular virus clone SIVsmmpBjI.9, cloned from isolate PBjI4 of simian immunodeficiency virus (SIV) from sooty mangabey monkeys (Cercocebus atys), leads to acute viral and often lethal disease within days or weeks. SIVsmmpBjl.g has the unique property of replicating in nonstimulated peripheral blood mononuclear cells from pig-tailed macaques. In contrast, molecular virus clone SIVagm3mc of SIV from African green monkeys (Cercopithecus aethiops), which is apathogenic in its natural host and in pig-tailed macaques, is unable to grow in nonstimulated peripheral blood cells. Chimeric proviruses were constructed by exchanging defined regions of SIVagm3mc against comparable regions of SIVsmmpBjl.9. Four of five hy- brid viruses generated by transfection into the CD4-positive T-cell line C8166 replicated in T-cell lines permissive for SIVagm3mc replication and in stimulated peripheral blood cells from pig-tailed macaques and from African green monkeys. Three hybrid viruses displayed the distinct biological prop- erty of SIVSmmPBjl4 to replicate in nonstimulated peripheral blood cells from pig-tailed macaques and from African green monkeys. Replication in nonstimulated peripheral blood cells was dependent on the presence of the U3 promoter region of SIVsmmPBjl.9 within the viral long terminal repeat.