RevM10-mediated inhibition of HIV-1 replication in chronically infected T cells

Abstract

Two clinical regimens have been proposed for gene therapies of acquired immunodeficiency syndrome (AIDS): (i) Genetic modification of differentiated peripheral mononuclear cells ex vivo and (ii) gene delivery into hematopoietic stem/progenitor cells ex vivo. Various antiviral strategies targeted at different molecular processes in the human immunodeficiency virus type 1 (HIV-1) life cycle are currently being pursued, all with the goal of reducing HIV-1 replication. Until now, all successful studies have reported inhibition in acutely HIV-infected cells that had been genetically modified prior to infection. These promising results do not address a clinically relevant question: What is the contribution of already infected peripheral mononuclear and hematopoietic stem/progenitor cells to disease progression? In this report, we demonstrate inhibition of both HIV-1 replication and production of infectious particles in chronically infected human T leukemia cell lines. The antiviral effect on the transduced cell population correlates with the expression of the dominant-negative RevM10 protein. This is the first demonstration that a gene therapy-based treatment can achieve antiviral efficacy in human T leukemia cells chronically infected with HIV-1.