Background:  Although SIV of chimpanzees (SIV_cpz) is now recognized as the precursor to HIV-1, even the most basic aspects of SIV_cpz infection in its natural host are unknown. Chimpanzees in Gombe National Park (Tanzania) have been under behavioral observation for almost 50 years, thus providing a unique opportunity to study the natural history of SIV_cpz infection in the wild.

Methods:  Fecal samples (n = 1022) were collected from habituated chimpanzees of 2 Gombe communities between October 2000 and July 2008. All samples were tested by Western blot analysis, and antibody-positive samples were subjected to real-time polymerase chain reaction (RT-PCR) to amplify SIV_cpz sequences. Sample provenance was confirmed by mitochondrial and microsatellite analyses. Age, death status, and maternal relationships were derived from observational data. Chimpanzee mortality was calculated using discrete event history methods and Cox proportional hazards regression models. Deceased chimpanzees were subjected to post-mortem analyses.

Results:  Between 2001 and 2007, prevalence rates in Gombe increased from 8% (3 of 40) to 17% (12 of 72). At first analysis, 7 chimpanzees harbored SIV_cpz, while 10 became infected during the study period. Virus genetic and observational data indicated that of the latter, 3 represented mother-to-infant and 7 horizontal transmissions. Infants born to SIV_cpz-infected mothers faced a higher mortality risk than infants born to uninfected mothers (p = 0.014). Moreover, SIV_cpz infection was associated with a significantly higher mortality rate. Infected chimpanzees had a 6- to 17-fold increased death hazard (using maximally and minimally conservative event definitions) compared to negative controls (p <0.001). Finally, histological analyses revealed clear evidence of CD4⁺ T cell depletion and lymphatic tissue destruction in 2 of 3 SIV_cpz-infected chimpanzees, but none of 4 uninfected controls.

Conclusions:  These findings are the first to show that SIV_cpz has a significant negative effect on chimpanzee health, survival, and reproduction, indicating that this virus is pathogenic in its natural host. Current mortality data place the pathogenicity of SIV_cpz lower than that of HIV-1 in humans, but substantially higher than that of HIV-2 in humans and SIV_smm in sooty mangabeys. This intermediate position may be key in deciphering which of the factors implicated in HIV-1 pathogenicity are primarily responsible for disease progression in humans.