Malaria infection induces virus expression in human immunodeficiency virus transgenic mice by CD4 T cell-dependent...

To test the capacity of malaria parasites to trigger virus expression in vivo, human immunodeficiency virus (HIV) transgenic mice were infected with Plasmodium chabaudi chabaudi clone AS. Splenocytes recovered during peak parasitemia showed a dramatic elevation in viral p24 production that returned to baseline by day 15 and failed to rebound at recrudescence or after reinfection. The major sources of virus expression were antigen-presenting cells (APCs) rather than T lymphocytes. Nevertheless, T cells from infected mice stimulated with plasmodial antigen triggered 5-10-fold increases in p24 production from dendritic cells in vitro, which suggests that viral induction stems from interaction of malaria-specific T lymphocytes with HIV-expressing APCs. Indeed, depletion of CD4 T cells resulted in a 70% reduction in the p24 response stimulated by malaria in vivo. These findings demonstrate the ability of Plasmodium species to immunologically activate latently integrated HIV in vivo but suggest that this process may be restricted to acute infection.