Viral activation from latency during retrodifferentiation of U937 cells exposed to phorbol ester followed by infection with human immunodeficiency virus type 1

Abstract

To determine the mechanism underlying the human immunodeficiency virus type 1 (HIV-1) latency and its activation in monocyte/macrophage lineage, the human promonocytic cell line U937 was infected with HIV-1 after differentiation with varied doses of phorbol 12-myristate 13-acetate (PMA). Variously differentiated intermediate stages were generated in U937 cells in a dose-dependent manner. When these cells were infected with lymphotropic HIV-1, the kinetics of the production of HIV-1 DNA, the appearance of HIV-1 antigen-positive cells, and viral production in the conditioned media were slower at higher doses of PMA. This different susceptibility to the infection was not due to the rate of HIV-1 adsorption. Viral replication from latency in the differentiated cells was activated in proportion with the retrodifferentiation observed in long-term cultures of the host cells. Thus, our data demonstrate the close correlation between the regulation of HIV-1 replication and the differentiation stage of monocyte/macrophage lineage cells at the time of HIV-1 infection. The retrodifferentiation phenomenon in infected cells seems to be particularly important for understanding the mechanisms for HIV-1 activation from latency.