Enhanced T cell engraftment after retroviral delivery of an antiviral gene in HIV-infected individuals.
Intracellular expression of gene products that inhibit viral replication have the potential to complement current antiviral approaches to the treatment of AIDS. We previously have shown that a mutant inhibitory form of an essential viral protein, Rev M10, prolongs the survival of T cells transduced with a nonviral vector in HIV-infected individuals. Because these gene-modified cells were not observed in patients beyond 8 weeks, efforts were made to improve the duration of engraftment. In this study, we used retroviral vector delivery of Rev M10 to CD4(+) cells and analyzed relevant immune responses in a pilot study of three HIV-seropositive patients. DNA and RNA PCR analyses revealed that cells transduced with Rev M10 retroviral vectors survived and expressed the recombinant gene for significantly longer time periods than those transduced with a negative control vector in all three patients. Immune responses were not detected either to Rev M10 or to Moloney murine leukemia virus gp70 envelope protein. Rev M10-transduced cells were detected for an average of 6 months after retroviral gene transfer compared with approximately 3 weeks for the previously reported nonviral vector delivery. These findings suggest that retroviral delivery of an antiviral gene may potentially contribute to immune reconstitution in AIDS and could provide a more effective vector to prolong survival of CD4(+) cells in HIV infection.
Ranga
U
U
Department of Internal Medicine, University of Michigan Medical Center, 1150 W. Medical Center Drive, 4520 MSRB I, Ann Arbor, MI 48109-0650, USA.
Woffendin
C
C
Verma
S
S
Xu
L
L
June
C H
CH
Bishop
D K
DK
Nabel
G J
GJ
D000818:Animals; D000906:Antibodies / Q000627:therapeutic use; D000998:Antiviral Agents / Q000627:therapeutic use; D017252:CD3 Complex / Q000276:immunology; D018791:CD4 Lymphocyte Count; D002470:Cell Survival; D002478:Cells, Cultured; D003131:Combined Modality Therapy; D015694:Gene Products, rev / Q000235:genetics* / Q000627:therapeutic use; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors; D006679:HIV Seropositivity / Q000276:immunology / Q000628:therapy*; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D007376:Interleukin-2 / Q000627:therapeutic use; D051379:Mice; D012190:Retroviridae; D013601:T-Lymphocytes / Q000276:immunology / Q000637:transplantation*; D054321:rev Gene Products, Human Immunodeficiency Virus
D000906:Antibodies; D000998:Antiviral Agents; D017252:CD3 Complex; D015694:Gene Products, rev; D007376:Interleukin-2; D054321:rev Gene Products, Human Immunodeficiency Virus