SUPPRESSION OF HIV REPLICATION IN HUMAN MONOCYTE-DERIVED MACROPHAGES INDUCED BY GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR

Susceptibility to HIV infection was examined in macrophages differenti ated from human monocytes by macrophage colony-stimulating factor (M-C SF) or granulocyte/macrophage colony-stimulating factor (GM-CSF), The replication of macrophage-tropic human immunodeficiency virus type-1 ( HIV-1), which was determined by reverse transcriptase (RT) activity, w as significantly suppressed in macrophages induced by GM-CSF (GM-type macrophages) but not in those induced by M-CSF (M-type macrophages). M ultinucleated giant cells were formed only in M-type macrophages after HIV infection, However, the expression of CD4 molecules on the surfac e of both types of macrophages was similar and the proviral DNA was de tectable in cell lysates of both macrophages, although the amount of p roviral DNA in M-type macrophages was higher than that in GM-type macr ophages, Many steps have been defined in HIV infection and replication , such as adsorption of HIV to the cell surface, internalization of th e viral core into the cytoplasm, uncoating of viral RNA, reverse trans cription and integration of proviral DNA into cellular DNA, transcript ion and translation of proviral DNA, assembly of viral components, and budding of virus particles, Our findings suggested that the suppressi on of HIV-1 replication in macrophages induced by GM-CSF is mainly due to a disturbance at certain steps of replication after synthesis of t he proviral DNA, Thus, the suppression of HIV replication in GM-type m acrophages may provide a model of the latency of HIV infection in vivo .