SIMIAN IMMUNODEFICIENCY VIRUS REPLICATES TO HIGH-LEVELS IN SOOTY MANGABEYS WITHOUT INDUCING DISEASE

A serologic survey of primates living in a French zoo allowed identifi cation of three cases of infection with simian immunodeficiency virus in sooty mangabeys (Cercorebus atys) (SIVsm). Viral isolates, which we re designated SIVsmFr66, SIVsmFr74 and SIVsmFr85, were obtained after short-term culture of mangabey lymphoid cells. Phylogenetic analysis o f gag and env sequences amplified directly from mangabey tissues showe d that the three SIVsmFr were genetically close and that they constitu ted a new subtype within the diverse SIVsm-SIVmac-human immunodeficien cy virus type 2 (HIV-2) group. We could reconstruct the transmission e vents that likely occurred in 1986 between the three animals and evalu ate the divergence of SIVsmFr sequences since transmission. The estima ted rate of mutation fixation was 6 x 10(-3) substitutions per site pe r year, which was as high as the rate found for SIVmac infection in ma caques. These data indicated that SIVsmFr replicated at a high rate in mangabeys, despite the nonpathogenic character of infection in this h ost. The viral load evaluated by competitive PCR reached 20,000 viral DNA copies per 10(6) lymph node cells. In addition, productively infec ted cells were readily detected in mangabey lymphoid tissues by in sit u hybridization. The amounts of viral RNA in plasma ranged from 10(5) to 10(7) copies per ml. The cell-associated and plasma viral loads wer e as high as those seen in susceptible hosts (humans or macaques) duri ng the asymptomatic stage of HIV or SIVmac infections. Thus, the lack of pathogenicity of SIVsm for its natural host cannot be explained by limited viral replication or by tight containment of viral production.