PLASMODIUM-FALCIPARUM ANTIGEN-INDUCED HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 REPLICATION IS MEDIATED THROUGH INDUCTION OF TUMOR-NECROSIS-FACTOR-ALPHA

Because malaria-stimulated cytokine production may have deleterious ef fects on human immunodeficiency virus type 1 (HIV-1) replication, the effects of Plasmodium falciparum antigens on HIV-1 replication were st udied. Stimulation with malarial antigens significantly enhanced HIV-1 replication of HIV-1(LAV) and primary HIV-1 isolates (subtype A) in C DS-depleted peripheral blood mononuclear cells from naive donors. The malarial antigen-induced activation of HIV-1 was due to cellular activ ation as judged by the expression of cell activation markers and proli ferative responses. While malarial antigen stimulation increased expre ssion of tumor necrosis factor (TNF-alpha) and interleukin-6 (IL-6), o nly monoclonal antibodies (MAbs) to TNF-alpha inhibited malarial antig en-induced HIV-1 replication, whereas MAb to IL-6 had no effect. Malar ial antigen increased HIV-1 replication by increasing viral mRNA expre ssion and by activating long terminal repeat-directed viral transcript ion. These data suggest that P. falciparum infection can modulate HIV- 1 pathogenesis by activating lymphocytes and stimulating viral replica tion through the production of cytokines.