RevM10-mediated inhibition of HIV-1 replication in chronically infected T cells.
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.
Escaich
S
S
Progenesys, Palo Alto, CA 94304, USA.
Kalfoglou
C
C
Plavec
I
I
Kaushal
S
S
Mosca
J D
JD
Böhnlein
E
E
D001483:Base Sequence; D002460:Cell Line; D018274:Electroporation; D015694:Gene Products, rev / Q000235:genetics*; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000737:chemistry / Q000235:genetics; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D009052:Leukemia Virus, Murine / Q000235:genetics; D015458:Leukemia, T-Cell; D008969:Molecular Sequence Data; D013601:T-Lymphocytes / Q000166:cytology / Q000821:virology*; D014407:Tumor Cells, Cultured; D014779:Virus Replication; D054321:rev Gene Products, Human Immunodeficiency Virus
D015694:Gene Products, rev; D054321:rev Gene Products, Human Immunodeficiency Virus