Simian immunodeficiency virus of chimpanzees (SIVcpz) is the precursor of human immunodeficiency virus type 1 (HIV-1), the cause of the AIDS pandemic (1-3). For the past decade, our group has studied SIVcpz infection of wild-living chimpanzees, combining non-invasive virus detection with studies of chimpanzee behavior, life history, fertility and mortality (1-60). These investigations have provided unprecedented insight into the biology and pathogenicity of SIVcpz (4-6), its prevalence and geographic distribution (7-9), its zoonotic potential (8, 10-12), and its ability to counteract potent human restriction factos (12-19). We also examined the ecology, behavior, genetics and population history of wild chimpanzees (20-42), and discovered novel viruses (43-45), parasites (46-50) and microbiota (51-56) in their fecal samples, including the precursors of other major human pathogens (46, 47, 57). Most of this work was conducted in Gombe National Park, the only field site in the world where SIVcpz infection can be studied in habituated chimpanzees at close range. In this application, we propose to capitalize on these findings, many of which are only now coming to fruition, and to continue to conduct non-invasive investigations of SIVcpz infected wild-living apes to aid their survival as well as to enhance human health. Our working hypothesis is that studies of the precursor of the human AIDS virus in its natural chimpanzee host will continue to reveal critical new insight into HIV/SIV pathogenesis and lead to new interventions that will benefit both humans and chimpanzees. Taking advantage of the unique ecology, existing knowledge base and research infrastructure in Gombe, we will continue to study the pathobiology of SIVcpz and its impact on the three resident chimpanzee communities, assessing for the first time the necessity and feasibility of interventions aimed at reducing SIVcpz transmission (Aim #1). We will also expand our field studies to the Greater Mahale Ecosystem (GME), which is home to ~2,500 highly endangered savanna chimpanzees, to determine to what extent SIVcpz has penetrated this much larger and more diverse population (Aim #1). To identify new barriers of zoonotic transmission, we will determine why adaptation of the Gag protein was required each time ape viruses crossed the species barrier to humans, and elucidate how one particular amino acid residue at position 30 of the viral matrix protein (Gag-30) increases SIVcpz resistance to type 1 interferons (IFNs) in human CD4+ T cells (Aim #2). Finally, we will explore whether monoclonal antibodies and immunoadhesins that potently neutralize diverse strains of HIV-1 can be used for vectored immunoprophylaxis and/or therapy to combat SIVcpz infection (Aim #3). Execution of these aims will not only uniquely complement ongoing pathogenesis, prevention and cure research in HIV-1, but will lay the groundwork for feasibility studies aimed at translating interventions developed for HIV-1 infected humans to benefit SIVcpz infected chimpanzees.

Public Health Relevance

Effective approaches are urgently needed to prevent and cure HIV-1 infection. SIVcpz, the precursor of pandemic HIV-1, causes immunodeficiency and AIDS in chimpanzees. Studying SIVcpz infection in its natural host provides a unique opportunity to compare and contrast the mechanisms of AIDS pathogenesis in man's closest relative. This approach has already uncovered invaluable insight into the origins, evolution and pathobiology of HIV-1, and may inform new approaches to prevent and eradicate HIV-1/AIDS.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project (R01)
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AIDS Immunology and Pathogenesis Study Section (AIP)
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Lawrence, Diane M
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University of Pennsylvania
Internal Medicine/Medicine
Schools of Medicine
United States
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Lonsdorf, Elizabeth V; Gillespie, Thomas R; Wolf, Tiffany M et al. (2018) Socioecological correlates of clinical signs in two communities of wild chimpanzees (Pan troglodytes) at Gombe National Park, Tanzania. Am J Primatol 80:
Barbian, Hannah J; Connell, Andrew Jesse; Avitto, Alexa N et al. (2018) CHIIMP: An automated high-throughput microsatellite genotyping platform reveals greater allelic diversity in wild chimpanzees. Ecol Evol 8:7946-7963
Loy, Dorothy E; Rubel, Meagan A; Avitto, Alexa N et al. (2018) Investigating zoonotic infection barriers to ape Plasmodium parasites using faecal DNA analysis. Int J Parasitol 48:531-542
Wetzel, Katherine S; Yi, Yanjie; Yadav, Anjana et al. (2018) Loss of CXCR6 coreceptor usage characterizes pathogenic lentiviruses. PLoS Pathog 14:e1007003
Terio, Karen A; Lonsdorf, Elizabeth V; Kinsel, Michael J et al. (2018) Oesophagostomiasis in non-human primates of Gombe National Park, Tanzania. Am J Primatol 80:
Barbian, Hannah J; Li, Yingying; Ramirez, Miguel et al. (2018) Destabilization of the gut microbiome marks the end-stage of simian immunodeficiency virus infection in wild chimpanzees. Am J Primatol 80:
Joas, Simone; Parrish, Erica H; Gnanadurai, Clement W et al. (2018) Species-specific host factors rather than virus-intrinsic virulence determine primate lentiviral pathogenicity. Nat Commun 9:1371
Stewart, Fiona A; Piel, Alexander K; Luncz, Lydia et al. (2018) DNA recovery from wild chimpanzee tools. PLoS One 13:e0189657
Plenderleith, Lindsey J; Liu, Weimin; MacLean, Oscar A et al. (2018) Adaptive Evolution of RH5 in Ape Plasmodium species of the Laverania Subgenus. MBio 9:
Barbian, Hannah J; Jackson-Jewett, Raven; Brown, Corrine S et al. (2017) Effective treatment of SIVcpz-induced immunodeficiency in a captive western chimpanzee. Retrovirology 14:35

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