Inhibition of HIV-1 replication by a Tat transdominant negative mutant in human peripheral blood lymphocytes from healthy donors and HIV-1-infected patients

Abstract

It was previously shown that a tat mutant (tat₂₂) where cysteine 22 is substituted by glycine behaves as a transdominant negative mutant in Jurkat T cells lytically or latently infected by HIV-1. In this study we demonstrate that tat₂₂ controls HIV-1 replication in primary cells. This effect was observed both after in vitro infection of peripheral blood mononuclear cells (PBMCs) from normal donors and after reactivation of the latent infection in PBMCs from seropositive patients. The antiviral effect of tat₂₂ was limited to conditions of low virus production. The use of tat₂₂ may be promising for a gene therapy approach to AIDS during the asymptomatic phase of the disease allowing control of virus replication in infected cells and inhibition of virus spread to uninfected cells.