In the Division of Comparative Pathology, Dr. O'Neil and colleagues use contemporary molecular histological techniques to study physiologic and pathologic processes in various species of Old and New World nonhuman primates. Dr. O'Neil makes use of nonhuman primate models to investigate the mucosal transmission of HIV, as well as the pathogenesis and treatment of AIDS.

A large number of infants in developing countries become infected with HIV through the ingestion of breast milk from infected mothers. Dr. O'Neil's group has found that in addition to the oral cavity, the stomach and intestine can serve as portals of virus entry after oral exposure. Elucidation of the mechanisms of oral HIV transmission will guide development of vaccines designed to protect nursing infants from HIV infection.

Certain species of nonhuman primates serve as natural hosts of simian immunodeficiency viruses (SIV). These natural hosts experience persistently high levels of SIV replication in lymphoid tissues, similar to that seen in HIV infected humans, but do not develop AIDS. Dr. O'Neil is comparing SIV infection in natural hosts with infections in non-adapted primate species that develop AIDS. Understanding the adaptive mechanisms that enable the natural hosts of SIV to resist the development of AIDS could provide important insight for the development of a vaccine against HIV.

Highly active antiretroviral therapy (HAART) significantly reduces the quantity of virus in blood and lymphoid tissues of many HIV-infected individuals, thereby protecting against the development of AIDS. HIV also replicates in the brain, but most antiretroviral agents can not cross the blood-brain barrier. Thus the brain may serve as a reservoir for virus during antiretroviral treatment. Dr. O'Neil is evaluating the effects of antiretroviral agents and the host immune response in reducing viral load in the brain. This work will aid the development of vaccines and antiretroviral regimens for individuals suffering from HIV-associated dementia.