HIV-1-INDUCED THYMOCYTE DEPLETION IS ASSOCIATED WITH INDIRECT CYTOPATHICITY AND INFECTION OF PROGENITOR CELLS IN-VIVO

Direct and indirect cytopathic mechanisms have been proposed to accoun t for the loss of CD4(+) T cells after infection with human immunodefi ciency virus type 1 (HIV-1). We report here that HIV-1 infection of th e human thymus in vivo results in thymocyte depletion by at least two different mechanisms. Thymocytes within multiple stages of differentia tion are induced to die of apoptosis; most of these cells are uninfect ed. Additionally, thymopoiesis is interrupted by direct infection and destruction of intrathymic CD3(-)CD4(+)CD8(-) progenitor cells. These mechanisms are differentially induced by distinct isolates of HIV-1.