Two studies published this month in the Journal of Clinical Investigation provide a significant advance in understanding how some species of monkeys such as sooty mangabeys and African green monkeys avoid AIDS when infected with SIV, the simian equivalent of HIV.

Using comparative genomics of SIV infection, researchers at the University of Pennsylvania School of Medicine, with collaborators from University of Minnesota, the University of Toronto, and Emory University, looked at sooty mangabeys, and a second group at the Pasteur Institute in France, looked at African green monkeys to identify possible genes related to disease progression or resistance.

“Sooty mangabeys are able to rapidly shut down the immune response after the initial SIV infection, and remain healthy. The mangabeys respond to SIV in a manner similar to rhesus macaques, which get sick, or to humans infected with HIV, but the mangabeys do not get sick,” says first author Steven E. Bosinger, PhD , a postdoctoral fellow in the Department of Pathology and Laboratory Medicine.

“The Penn study is a step forward in understanding why some African monkeys do not get sick when they are infected with SIV, which is a key question in contemporary AIDS research,” says senior author Guido Silvestri, MD, associate professor of Pathology and Laboratory Medicine and Director of Clinical Virology.

The Penn study compared changes induced by SIV infection on the overall profile of gene expression in two species of monkeys: rhesus macaques, which undergo an AIDS-like disease when infected with SIV, and sooty mangabeys, which, in stark contrast, remain AIDS-free despite life-long infection. Sooty mangabeys, which are native to Western Africa and infected naturally in the wild, were previously believed by some to remain asymptomatic because of a genetic inability to mount innate immune responses to SIV, and in particular, to produce type I interferons.

However, the current studies change the way AIDS researchers think about human versus simian AIDS infection. The sooty mangabeys’ robust antiviral immune response upon SIV infection, including a massive up-regulation of interferon response genes, or ISGs, indicates production of type I interferons in the mangabeys. Of note, this antiviral response is transient, as seen in sooty mangabeys, lasting for about four weeks, but remains constant over time in rhesus macaques, which may contribute to the immunodeficiency seen in this species. SIV induces a massive activation of immune molecules in both species, but only sooty mangabeys are able to bring the response under control.

In addition, by comparing the changes induced by SIV infection on the overall profile of gene expression of rhesus macaques versus sooty mangabeys, the research teams identified genes whose expression may be responsible for disease progression or, alternatively, disease resistance. These genes may provide novel targets for AIDS therapy.

Penn Medicine is one of the world’s leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the University of Pennsylvania School of Medicine (founded in 1765 as the nation’s first medical school) and the University of Pennsylvania Health System, which together form a $3.6 billion enterprise.

Penn’s School of Medicine is currently ranked #3 in U.S. News & World Report’s survey of research-oriented medical schools, and is consistently among the nation’s top recipients of funding from the National Institutes of Health, with $367.2 million awarded in the 2008 fiscal year.

Penn Medicine’s patient care facilities include:

– The Hospital of the University of Pennsylvania the nation’s first teaching hospital, recognized as one of the nation’s top 10 hospitals by U.S. News & World Report

– Penn Presbyterian Medical Center named one of the top 100 hospitals for cardiovascular care by Thomson Reuters

– Pennsylvania Hospital the nation’s first hospital, founded in 1751, nationally recognized for excellence in orthopaedics, obstetrics & gynecology, and behavioral health.

Additional patient care facilities and services include Penn Medicine at Rittenhouse, a Philadelphia campus offering inpatient rehabilitation and outpatient care in many specialties; as well as a primary care provider network; a faculty practice plan; home care and hospice services; and several multispecialty outpatient facilities across the Philadelphia region.

Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2008, Penn Medicine provided $282 million to benefit our community.

Source: University of Pennsylvania School of Medicine

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