Beatrice Hahn, M.D.
Professor of Medicine and Microbiology
409 Johnson Pavilion
3610 Hamilton Walk
Department of Microbiology
Perelman School of Medicine
University of Pennsylvania
Philadelphia, PA 19104
National Academy of Sciences Research Briefing "Deciphering the Origins of AIDS and Malaria"
My laboratory has had a long-standing interest in elucidating the origins and evolution of human and simian immunodeficiency viruses, and in studying HIV/SIV gene function and disease mechanisms from an evolutionary perspective. Characterizing the evolutionary relationships of simian immunodeficiency viruses infecting different non-human primate species in sub-Saharan Africa, we found that Acquired Immunodeficiency Syndrome (AIDS) – one of the most devastating infectious diseases to have emerged in recent history – was the result of cross-species infections of humans by lentiviruses of primate origin. Specifically, we discovered that HIV-1 resulted from cross-species infections of SIVcpz and SIVgor naturally infecting chimpanzees (Pan troglodytes) and gorillas (Gorilla gorilla), respectively, while HIV-2 resulted from transmissions of SIVsmm infecting sooty mangabeys (Cercocebus atys). Moreover, we found that these viruses had entered the human population on multiple occasions, although only one of these transfers had spawned the HIV-1 pandemic. As we now know from molecular clock analyses, the main group of HIV-1, which has afflicted more than 70 million people and caused more than 30 million deaths worldwide, was transmitted to humans in the first third of the 20th century.
To further characterize the primate reservoirs of HIV-1 and HIV-2, we developed non-invasive methods of SIV detection and characterization. These novel (urine and fecal based) methods allowed us to pinpoint the geographic origin of epidemic HIV-2, trace the source of pandemic (group M) and non-pandemic (group N) HIV-1 to geographically isolated chimpanzee communities in southern Cameroon, and discover in wild gorilla populations viruses closely related to HIV-1 group O. We also performed the first natural history study of SIVcpz in Gombe National Park, determining the prevalence, transmission patterns and pathogenicity of this virus in both habituated and non-habituated chimpanzee communities. Combining virological, ecological, behavioral and necropsy data from over a decade, we found that SIVcpz, like HIV-1, causes significantly increased mortality and AIDS-like immunopathology in wild chimpanzees. We also found that in at least one instance high SIVcpz prevalence rates contributed to the decline of a chimpanzee community. This was a surprising finding, since until then it had been assumed for a long time that SIVcpz was non-pathogenic in its natural host.
Most recently, we have employed our non-invasive detection methods to determine the origin of the human malaria parasite Plasmodium falciparum. Screening ~3,000 ape fecal samples from 60 field sites in central Africa, we found Plasmodium spp. infection in chimpanzees (Pan troglodytes) and western gorillas (Gorilla gorilla), but not in eastern gorillas (Gorilla beringei) or bonobos (Pan paniscus). Ape Plasmodium infections were highly prevalent, widely distributed, and almost always comprised of mixed parasite species. Phylogenetic analyses of full-length Plasmodium mitochondrial sequences revealed that human P. falciparum is of gorilla origin, and not as previously reported of chimpanzee, bonobo or ancient human origin. Moreover, just like for HIV-1, we found that pandemic P. falciparum had resulted from a single cross-species transmission event.
In the future, we will continue to work on emerging infectious diseases and build basic and translational research programs in global health. Current projects involve:
- Studies of HIV-1 transmission. We have devised a way to infer the nucleotide sequence of HIV-1 strains that are responsible for initiating productive infection. We are interested in determining whether these transmitted/founder viruses have unique biological properties that render them uniquely suited for mucosal transmission.
- Studies of ape Plasmodium infections. We will investigate whether African apes represent a recurrent source of human infection by characterizing potential ape reservoirs and using 454 sequencing to detect ape Plasmodium in humans at risk for such infections.
- Studies of SIVcpz infection of wild chimpanzees. We are interested in the impact of SIVcpz infection on chimpanzee population dynamics and will continue our natural history studies in Gombe National Park and other sites in Tanzania.
- Studies in HIV vaccine development. We are interested in examining new platforms for HIV immunogen design and delivery.
Dr. Hahn in Gombe Reserve, 2009
Members of the Hahn Lab
Current members of the Hahn lab, with the month and the year they joined the lab, their previous institution, and a brief description of their projects (updated summer 2011):
Research Assistant Professors:
Weimin Liu, M.D. (06/02) Plasmodium infections of wild apes
Yingying Li, M.D. (06/97) Molecular epidemiology of SIVcpz in wild-living chimpanzees
Gerald H. Learn, Ph.D. (03/08) Molecular evolution of HIV/SIV and ape Plasmodium infections
Erica L.H. Parrish (10/10)
Nicholas F. Parrish (8/09) B.S., Emory University. Biological phenotype of transmitted founder HIV-1
Shilpa S. Iyer (8/10) B.S., Fergusson College, M.S. University of Pune, Pune, India. Fitness costs associated with HIV-1 immune escape
Sesh Sundararaman (3/11) B.S., Williams College. Great ape reservoirs of human malaria.
Miguel Ramirez (08/11)
Andrew G. Smith (07/11)
Lilly Kong, D.V.M., Chief Scientific Officer, PrimeraDx
Scott Michael, Ph.D., Associate Professor, Florida Gulf Coast University
John Kappes, Ph.D., Associate Professor, University of Alabama
Feng Gao, M.D., Professor, Duke University
Thomas Fletcher, Ph.D., Chief Scientific Officer, Immugen Pharmaceuticals, Inc.
Sundarasamy Mahalingam, Ph.D., Associate Professor, Indian Institute of Technology Madras, India
David Robertson, Ph.D., Senior Lecturer, University of Manchester, United Kingdom
Brandon Keele, Ph.D., Senior Scientist SAIC-Frederick, NCI-Frederick
Yuexia Li, Ph.D., Senior Director of Quality Systems, Tetracore, Inc
Stanley Trask, M.S., Research Scientist, Affymetix
Marcelo Soares, Ph.D., Professor of Genetics, Universidade Federal do Rio de Janeiro, Brazil
Mario L. Santiago, Ph.D., Assistant Professor, University of Colorado
Rebecca Rudicell, Ph.D., Postdoctoral Fellow, Vaccine Research Center, NIH