Increased mortality and AIDS-like immunopathology in wild chimpanzees infected with SIVcpz

Abstract

African primates are naturally infected with over 40 different simian immunodeficiency viruses (SIVs), two of which have crossed the species barrier and generated human immunodeficiency virus types 1 and 2 (HIV-1 and HIV-2)1,2. Unlike the human viruses, however, SIVs do not generally cause acquired immunodeficiency syndrome (AIDS) in their natural hosts3. Here we show that SIVcpz, the immediate precursor of HIV-1, is pathogenic in free-ranging chimpanzees. By following 94 members of two habituated chimpanzee communities in Gombe National Park, Tanzania, for over 9 years, we found a 10- to 16-fold higher age-corrected death hazard for SIVcpz-infected (n = 17) compared to uninfected (n = 77) chimpanzees. We also found that SIVcpz-infected females were less likely to give birth and had a higher infant mortality rate than uninfected females. Immunohistochemistry and in situ hybridization of post-mortem spleen and lymph node samples from three infected and two uninfected chimpanzees revealed significant CD4+ T-cell depletion in all infected individuals, with evidence of high viral replication and extensive follicular dendritic cell virus trapping in one of them. One female, who died within 3 years of acquiring SIVcpz, had histopathological findings consistent with end-stage AIDS. These results indicate that SIVcpz, like HIV-1, is associated with progressive CD4+ T-cell loss, lymphatic tissue destruction and premature death. These findings challenge the prevailing view that all natural SIV infections are non-pathogenic and suggest that SIVcpz has a substantial negative impact on the health, reproduction and lifespan of chimpanzees in the wild.

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Figure 1: SIVcpz prevalence in Gombe.
Figure 2: SIVcpz-associated mortality in Gombe.
Figure 3: Histopathology of end-stage SIVcpz infection.
Figure 4: CD4 + T-cell depletion in SIVcpz-infected chimpanzees.

Accession codes

Data deposits

Newly derived SIVcpz sequences have been deposited in the GenBank database under accession numbers FJ895381–FJ895405.

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Acknowledgements

We thank the field staff at the Gombe Stream Research Centre for collecting behavioural data as well as urine and faecal samples from wild chimpanzees; E. Kaaya for help with necropsies; A. Collins for logistical support; the Tanzania Commission for Science and Technology, the Tanzania Wildlife Research Institute, and the Tanzania National Parks for permission to conduct research in Gombe; I. White for discussions; L. Lowenstine for histological consultation; M. Salazar and Y. Chen for technical assistance; and J. C. White for artwork and manuscript preparation. This work was supported by grants from the National Institutes of Health (R01 AI50529, R01 AI58715, U19 AI067854, T32 GM008111), the National Cancer Institute (contract HHSN266200400088C), the UAB Center for AIDS Research (P30 AI 27767), the Yerkes National Primate Research Center (RR-00165), the National Science Foundation (DBS-9021946, SBR-9319909, BSC-0452315, IIS-0431141, BSC-0648481), the Jane Goodall Institute, the Harris Steel Group, the University of Minnesota, the University of Illinois, the US Fish and Wildlife Service Great Ape Conservation Fund, the Windibrow, Arcus, Guthman and Davee Foundations, and the Lincoln Park Zoo. R.S.R. was funded by a Howard Hughes Medical Institute Med-into-Grad Fellowship. The content of this publication does not necessarily reflect the views or policies of the US Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government.

Author Contributions All authors contributed to the acquisition, analysis and interpretation of the data; B.F.K., A.E.P., J.G., G.M.S., P.M.S. and B.H.H. initiated and conceived the study; B.F.K., R.S.R., Y.L. and E.W. performed non-invasive SIVcpz screening and genetic analyses; J.H.J., J.S.-S., M.L.W. and A.E.P. analysed chimpanzee fertility and mortality; K.A.T., M.J.K., J.R., D.A.T. and T.M. performed necropsies; K.A.T. and J.D.E performed immunohistochemistry and in situ hybridization studies; G.H.L. and P.M.S. performed phylogenetic analyses; J.H.J., T.M.B. and P.M.S. performed statistical analyses; M.L.W., A.M., S.K., E.V.L. and D.A.T. conducted and supervised all fieldwork. J.G.E. and G.S. provided data on captive sooty mangabeys; and B.F.K., A.E.P., P.M.S., G.M.S. and B.H.H. coordinated the contributions of all authors and wrote the paper. B.F.K., J.H.J., K.A.T., J.D.E., R.S.R. and M.L.W. contributed equally to this paper.

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Correspondence to Beatrice H. Hahn.

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Keele, B., Jones, J., Terio, K. et al. Increased mortality and AIDS-like immunopathology in wild chimpanzees infected with SIVcpz. Nature 460, 515–519 (2009). https://doi.org/10.1038/nature08200

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