One of the great enduring mysteries in disease ecology is the timing of the AIDS pandemic. AIDS emerged as a clinical entity in the late 1970s, but HIV-1, the retrovirus that causes pandemic AIDS, entered the human population from wild primates many decades earlier, probably near the turn of the 20* century. Where was HIV during this long interval? We propose a novel ecological model for the delayed emergence of AIDS. Conceptually, in a metapopulation consisting of multiple, loosely interconnected sub-populations, a pathogen could persist at low levels indefinitely through a dynamic balance between localized transmission, localized extinction, and long-distance migration between sub-populations. This situation might accurately describe a network of villages in which population sizes are small and rates of migration are low, as would have been the case in Sub-Saharan Africa over a century ago. We will test our model in a highly relevant non-human primate system. In 2009, we documented three simian retroviruses co-circulating in a metapopulation of wild red colobus monkeys {Procolobus rufomitratus) in Kibale National Park, Uganda, where we have conducted research for over two decades. We will collect detailed data on social interactions, demography, health, and infection from animals in a core social group. We will also study a series of 20 red colobus sub-populations, each inhabiting a separate, isolated forest fragment. We will determine the historic connectivity ofthese sub-populations using a time series of remotely sensed images of forest cover going back to 1955, as well as using population genetic analyses of hypervariable nuclear DNA markers. We will assess the infection status of each animal over time and use viral molecular data to reconstruct transmission pathways. Our transmission models will define the necessary conditions for a retrovirus to persist, but they will not be sufficient to explain why a retrovirus might emerge. This is because human social factors ultimately create the conditions that allow zoonotic diseases to be transmitted from animal reservoirs and to spread. We will therefore conduct an integrated analysis ofthe root eco-social drivers of human-primate contact and zoonotic transmission in this system. We will study social networks to understand how social resources structure key activities relevant to human-primate contact and zoonotic transmission risk, and we will explore knowledge, beliefs, and perceptions of human-primate contact and disease transmission for a broad sample of the population. We will reconcile perceived risk with actual risk through a linked human health sun/ey and diagnostic testing for zoonotic primate retroviruses. The ultimate product of our research will a data-driven set of transmission models to explain the long-term persistence of retroviruses within a metapopulation of hosts, as well as a linked analysis of how human social factors contribute to zoonotic infection risk in a relevant Sub-Saharan African population. Our study will elucidate not only the origins of HIV/AIDS, but also how early-stage zoonoses in general progress from 'smoldering' subclinical infections to full-fledged pandemics.

Public Health Relevance

AIDS emerged as a pandemic long after HIV entered the human population from African primates, but the reasons for this delayed emergence are unknown. This project will examine the transmission of simian retroviruses in Ugandan monkeys in order to understand how primate behavior and ecology allow the long-term persistence and eventual emergence of these important pathogens. Through linked studies of local people, the project will identify how human social factors contribute to the cross-species transmission of simian retroviruses, thus providing critical information for preventing the future emergence of primate-borne diseases.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
1R01AI098420-01
Application #
8256865
Study Section
Special Emphasis Panel (ZRG1-BDCN-T (80))
Program Officer
Sharma, Opendra K
Project Start
2011-09-01
Project End
2016-08-31
Budget Start
2011-09-01
Budget End
2012-08-31
Support Year
1
Fiscal Year
2011
Total Cost
$503,765
Indirect Cost
Name
University of Wisconsin Madison
Department
Pathology
Type
Schools of Veterinary Medicine
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
Weny, Geoffrey; Okwee-Acai, James; Okech, Samuel George et al. (2017) Prevalence and Risk Factors Associated with Hemoparasites in Cattle and Goats at the Edge of Kibale National Park, Western Uganda. J Parasitol 103:69-74
Simons, Noah D; Eick, Geeta N; Ruiz-Lopez, Maria J et al. (2017) Cis-regulatory evolution in a wild primate: Infection-associated genetic variation drives differential expression of MHC-DQA1 in vitro. Mol Ecol 26:4523-4535
Simons, Noah D; Ruiz-Lopez, Maria Jose; Chapman, Colin A et al. (2016) Rapid Identification of Major Histocompatibility Complex Class I Haplotypes Using Deep Sequencing in an Endangered Old World Monkey. Conserv Genet Resour 8:23-26
Lauck, Michael; Bailey, Adam L; Andersen, Kristian G et al. (2015) GB virus C coinfections in west African Ebola patients. J Virol 89:2425-9
Chapman, Colin A; van Bavel, Bianca; Boodman, Carl et al. (2015) Providing health care to improve community perceptions of protected areas. Oryx 49:636-642
Genomic Resources Development Consortium; Blanchet, Simon; Bouchez, Olivier et al. (2015) Genomic resources notes accepted 1 December 2014 - 31 January 2015. Mol Ecol Resour 15:684
Paige, Sarah B; Malavé, Carly; Mbabazi, Edith et al. (2015) Uncovering zoonoses awareness in an emerging disease 'hotspot'. Soc Sci Med 129:78-86
Osazuwa-Peters, Oyomoare L; Jiménez, Iván; Oberle, Brad et al. (2015) Selective logging: do rates of forest turnover in stems, species composition and functional traits decrease with time since disturbance? - A 45 year perspective. For Ecol Manage 357:10-21
Lauck, Michael; Alkhovsky, Sergey V; Bào, Y?míng et al. (2015) Historical Outbreaks of Simian Hemorrhagic Fever in Captive Macaques Were Caused by Distinct Arteriviruses. J Virol 89:8082-7
Ghai, Ria R; Simons, Noah D; Chapman, Colin A et al. (2014) Hidden population structure and cross-species transmission of whipworms (Trichuris sp.) in humans and non-human primates in Uganda. PLoS Negl Trop Dis 8:e3256

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