Expression of a protective gene-prolongs survival of T cells in human immunodeficiency virus-infected patients.
The resistance of acquired immunodeficiency syndrome (AIDS) to traditional drug therapy has prompted a search for alternative treatments for this disease. One potential approach is to provide genetic resistance to viral replication to prolong latency. This strategy requires the definition of effective antiviral genes that extend the survival of T cells in human immunodeficiency virus (HIV)-infected individuals. We report the results of a human study designed to determine whether a genetic intervention can prolong the survival of T cells in HIV-infected individuals. Gene transfer was performed in enriched CD4+ cells with plasmid expression vectors encoding an inhibitory Rev protein, Rev M10, or a deletion mutant control, deltaRev M10, delivered by gold microparticles. Autologous cells separately transfected with each of the vectors were returned to each patient, and toxicity, gene expression, and survival of genetically modified cells were assessed. Cells that expressed Rev M10 were more resistant to HIV infection than those with deltaRev M10 in vitro. In HIV-infected subjects, Rev M10-transduced cells showed preferential survival compared to deltaRev M10 controls. Rev M10 can therefore act as a specific intracellular inhibitor that can prolong T-cell survival in HIV-1-infected individuals and potentially serve as a molecular genetic intervention which can contribute to the treatment of AIDS.
Woffendin
C
C
Howard Hughes Medical Institute, University of Michigan Medical Center, Ann Arbor 48109-0650, USA.
Ranga
U
U
Yang
Z
Z
Xu
L
L
Nabel
G J
GJ
D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000401:mortality / Q000628:therapy; D001483:Base Sequence; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000473:pathology / Q000502:physiology*; D002470:Cell Survival; D017931:DNA Primers; D015694:Gene Products, rev / Q000096:biosynthesis* / Q000235:genetics; D018014:Gene Transfer Techniques; D015757:Genes, rev; D015316:Genetic Therapy; D005822:Genetic Vectors; D015658:HIV Infections / Q000276:immunology* / Q000401:mortality / Q000628:therapy*; D015497:HIV-1; D006801:Humans; D017710:Lymphocyte Transfusion; D008297:Male; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D017384:Sequence Deletion; D015996:Survival Rate; D013601:T-Lymphocytes / Q000473:pathology / Q000502:physiology*; D054321:rev Gene Products, Human Immunodeficiency Virus
D017931:DNA Primers; D015694:Gene Products, rev; D054321:rev Gene Products, Human Immunodeficiency Virus