The roles of the macrophage in the pathogenesis of AIDS and the effects of HIV infection on macrophage function are only poorly understood. Macrophages may play a role in the latency of HIV infection. The proposed studies will consist of detailed analysis of macrophage function during in vitro HIV infection. We will emphasize studies on the interaction between HIV and protozoan macrophage parasites. The development of these parasites in normal and HIV-infected macrophages will be compared. 1) We will evaluate the capacity of HIV-infected macrophages to become activated to kill these parasites. We will also perform functional tests of macrophage activation, comparing the ability of normal and infected macrophages to become activated by external stimuli, including cytokines. Tests for activation include generation of H202 and cytokine and cytokine receptor expression. 2) In addition, we will compare normal and HIV-infected macrophages for their ability to present microbial antigens to autologous T cells. 3) We will examine the effects of exogenous cytokine or the intramacrophage persistence and replication of HIV. Recombinant cytokines, particularly those known to activate macrophages, will be added to cultures of HIV- infected macrophages and monocytes. These cells will be analyzed using light microscopy, electron microscopy, and nucleic acid probes to observe increase or decrease in HIV numbers, as well as changes in HIV location in the macrophage. These assays, in addition to the use of sensitive viral detection techniques, will evaluate the potential of free or liposome-encapsulated cytokines, alone and in combination, as therapeutics for HIV infection.
| Akridge, R E; Reed, S G (1996) Interleukin-12 decreases human immunodeficiency virus type 1 replication in human macrophage cultures reconstituted with autologous peripheral blood mononuclear cells. J Infect Dis 173:559-64 |
| Akridge, R E; Oyafuso, L K; Reed, S G (1994) IL-10 is induced during HIV-1 infection and is capable of decreasing viral replication in human macrophages. J Immunol 153:5782-9 |
| Silva, J S; Barral-Netto, M; Reed, S G (1993) Aggravation of both Trypanosoma cruzi and murine leukemia virus by concomitant infections. Am J Trop Med Hyg 49:589-97 |
| Reed, S G; da Silva, J S; Ho, J L et al. (1992) Cytokine activation of human macrophages infected with HIV-1 to inhibit intracellular protozoa. J Acquir Immune Defic Syndr 5:666-75 |
