Pathogenesis of HIV-1-Associated Processes

             Individuals infected with HIV-1 are at high risk for developing malignancies and other AIDS-associated complications, such as neurological deficits including dementia.  The pathogenetic mechanisms by which these processes occur is unknown, but investigator-initiated as well as collaborative studies indicate that viral integration may play a role in a subset of these disease processes.  Our research has focused on characterizing viral integration in a subset of both adult and pediatric tumors.  In collaboration with investigators at the University of California at San Francisco, analysis of cerebrospinal fluid has been shown to contain clonally infected macrophages with integration near the gene for platelet-derived growth factor-B.  The goal during the coming year will be to characterize the growth-regulating genes adjacent to sites of viral integration in clonal populations of macrophages and to determine the mechanisms by which HIV-1 disrupts cellular function.

             Ongoing collaborations continue with Dr. Deborah Lyn (Morehouse School of Medicine) to study peripheral blood macrophages to identify sites of integration that may be important in other AIDS-associated complications; with Dr. Michael McGrath (University of California at San Francisco) to study trafficking patterns of HIV-1 in the central nervous system and blood; with Dr. Brian Herndier (University of California at San Francisco) to characterize the immunological response to human herpesvirus 8 (or Kaposiâs sarcoma-associated herpesvirus); and with Dr. Julius Lecciones (Makati Medical Center, Manila, Philippines) to collect and analyze HIV-1-associated tumors from a cohort of HIV-1-infected patients from the Philippines.

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