Targeted inhibition of immunodeficiency virus replication in lymphocytes through retroviral mediated gene transfer.
To test the feasibility of gene therapy for AIDS patients, an animal model is needed to evaluate the efficacy and safety of this approach. Antiviral genes (encoding antisense RNA or viral protein) derived from Simian immunodeficiency virus (SIV) were efficiently targeted into CD4+ lymphocytes through retroviral-mediated gene transfer. After challenging with infectious viruses, the transduced lymphocytes that received antiviral genes were not only protected from SIV infection, but also from infection with HIV, for at least 25 days. Furthermore, little or no cytolytic effect (syncytium formation) was observed in the protected cells. These data demonstrated that SIV or HIV replication could be effectively blocked by antisense sequence(s) or negative dominant factors which were introduced into targeted cells through retroviral-mediated gene transfer.
Tung
F Y
FY
Department of Pathology, University of Florida, College of Medicine, Gainesville.
Daniel
M D
MD
D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D015496:CD4-Positive T-Lymphocytes / Q000382:microbiology*; D002460:Cell Line; D003588:Cytopathogenic Effect, Viral; D017931:DNA Primers / Q000737:chemistry; D004195:Disease Models, Animal; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors; D015726:Giant Cells / Q000382:microbiology; D015658:HIV Infections / Q000628:therapy; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D008251:Macaca; D008969:Molecular Sequence Data; D016372:RNA, Antisense / Q000032:analysis / Q000235:genetics; D012367:RNA, Viral / Q000032:analysis; D012194:RNA-Directed DNA Polymerase / Q000032:analysis; D015183:Restriction Mapping; D012190:Retroviridae; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000502:physiology*; D014161:Transduction, Genetic; D014779:Virus Replication / Q000235:genetics*
D017931:DNA Primers; D016372:RNA, Antisense; D012367:RNA, Viral; D012194:RNA-Directed DNA Polymerase