Restoration of cell surface CD4 expression in human immunodeficiency virus type 1-infected cells by treatment with a Tat antagonist

Abstract

Productive infection of T lymphocytes with human immunodeficiency virus type 1 (HIV-1) is accompanied by a diminution of surface CD4 receptors. Treatment of chronically HIV-1-infected CD4-negative T cells in vitro with the Tat antagonist Ro 5-3335 resulted in a drug dose-dependent decrease in virus protein production and a reciprocal increase in surface CD4 display. The drug-treated cells remained viable, showed significantly reduced levels of the full-length and spliced HIV-1 mRNAs as detected by Northern (RNA) blot hybridization, and maintained integrated HIV-1 DNA. In immunoprecipitation studies with drug-treated cells, the levels of free 55-kDa CD4 protein increased and gp160 complexed with CD4 decreased in amount. These results show for the first time that certain cytopathogenic effects of chronic HIV-1 infection can be reversed by suppressing virus expression.