Malaria infection induces virus expression in human immunodeficiency virustransgenic mice by CD4 T cell-dependent immune activation

To test the capacity of malaria parasites to trigger virus expression in vi vo, human immunodeficiency virus (HIV) transgenic mice were infected with P lasmodium chabaudi chabaudi clone AS. Splenocytes recovered during peak par asitemia showed a dramatic elevation in viral p24 production that returned to baseline by day 15 and failed to rebound at recrudescence or after reinf ection. 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 pr oduction from dendritic cells in vitro, which suggests that viral induction stems from interaction of malaria-specific T lymphocytes with HIV-expressi ng APCs. Indeed, depletion of CD4 T cells resulted in a 70% reduction in th e p24 response stimulated by malaria in vivo. These findings demonstrate th e ability of Plasmodium species to immunologically activate latently integr ated HIV in vivo but suggest that this process may be restricted to acute i nfection.