RESTRICTED EXPRESSION OF HIV-1 IN HUMAN ASTROCYTES - MOLECULAR-BASIS FOR VIRAL PERSISTENCE IN THE CNS

Besides macrophages and microglial cells, cells of astroglial origin a re thought to be targets of HIV1 in the brain. HIV1 infection of astro glial cells results in restricted production of the virus. To analyse the molecular basis of this restricted infection phenotype, we establi shed a chronically HIV1-infected low-producer astrocytoma cell line. T hese cells show only low levels of mRNA encoding structural proteins, due to a cell-determined blockage in the Rev/RRE regulatory axis. The low-producer state could not be overcome by treatment with known stimu lators of virus expression such as phorbol ester, (12-O-tetradecanoylp horbol-13-acetate), tumour necrosis factor alpha or sodium butyrate. T his indicates that the molecular mechanisms involved in restricting vi rus production in astroglial cells differ from those in latently infec ted T cells and monocytes.