How HIV-1 inhibits phagocytosis by macrophages

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Last year an estimated 3.1 million people died of AIDS (source: UNAIDS, Dec 2002) equivalent to the number killed by tuberculosis and malaria combined. AIDS-related opportunistic infections (OIs) are the main cause of death for AIDS patients, especially in resource constrained countries where access to antiretroviral and antibiotic therapy is limited. Attempts to limit the epidemic have failed and new foci have emerged in Eastern Europe, Central Asia and, of particular relevance for us, South East Asia, underlining the fact that safe and effective treatment for AIDS-related OIs will be a global health priority for the foreseeable future. People with healthy immune systems do not get OIs since the germs that cause such infections are efficiently ingested and subsequently destroyed by cells called macrophages. We have discovered that the virus that causes AIDS, HIV-1, interferes with the ability of macrophages to ingest opportunistic pathogens by the 2 most important mechanisms used for this purpose. We believe that this is the direct cause for the susceptibility of AIDS patients to many of the opportunistic pathogens that cause their OIs. The purpose of this grant will be to understand the biochemical basis underlying these 2 defects in macrophage function. This will help in the design of safe, adjunctive therapies aimed at improving macrophage function and reducing the risk of HIV-infected individuals developing AIDS-related OIs.