REVM10-MEDIATED INHIBITION OF HIV-1 REPLICATION IN CHRONICALLY INFECTED T-CELLS

Two clinical regimens have been proposed for gene therapies of acquire d inmunodeficiency syndrome (AIDS): (i) Genetic modification of differ entiated peripheral mononuclear cells ex vivo and (ii) gene delivery i nto hematopoietic stem/progenitor cells ex vivo, Various antiviral str ategies targeted at different molecular processes in the human immunod eficiency virus type 1 (HIV-1) life cycle are currently being pursued, all with the goal of reducing HIV-1 replication, Until now, all succe ssful studies have reported inhibition in acutely HIV-infected cells t hat had been genetically modified prior to infection, These promising results do not address a clinically relevant question: What is the con tribution of already infected peripheral mononuclear and hematopoietic stem/progenitor cells to disease progression? In this report, we demo nstrate inhibition of both HIV-1 replication and production of infecti ous particles in chronically infected human T leukemia cell lines, The antiviral effect on the transduced cell population correlates with th e expression of the dominant-negative RevM10 protein, This is the firs t demonstration that a gene therapy-based treatment can achieve antivi ral efficacy in human T leukemia cells chronically infected with HIV-1 .