Inhibition of clinical human immunodeficiency virus (HIV) type 1 isolates in primary CD4+ T lymphocytes by retroviral vectors expressing anti-HIV genes.
Gene therapy may be of benefit in human immunodeficiency virus type 1 (HIV-1)-infected individuals by virtue of its ability to inhibit virus replication and prevent viral gene expression. It is not known whether anti-HIV-1 gene therapy strategies based on antisense or transdominant HIV-1 mutant proteins can inhibit the replication and expression of clinical HIV-1 isolates in primary CD4+ T lymphocytes. We therefore transduced CD4+ T lymphocytes from uninfected individuals with retroviral vectors expressing either HIV-1-specific antisense-TAR or antisense-Tat/Rev RNA, transdominant HIV-1 Rev protein, and a combination of antisense-TAR and transdominant Rev. The engineered CD4+ T lymphocytes were then infected with four different clinical HIV-1 isolates. We found that replication of all HIV-1 isolates was inhibited by all the anti-HIV vectors tested. Greater inhibition of HIV-1 was observed with transdominant Rev than with antisense RNA. We hereby demonstrated effective protection by antisense RNA or transdominant mutant proteins against HIV-1 infection in primary CD4+ T lymphocytes using clinical HIV-1 isolates, and this represents an essential step toward clinical anti-HIV-1 gene therapy.
VandenDriessche
T
T
Clinical Gene Therapy Branch, National Cancer Institute, Bethesda, Maryland 20892, USA.
Chuah
M K
MK
Chiang
L
L
Chang
H K
HK
Ensoli
B
B
Morgan
R A
RA
D000163:Acquired Immunodeficiency Syndrome / Q000628:therapy*; D015496:CD4-Positive T-Lymphocytes / Q000821:virology*; D015316:Genetic Therapy; D005822:Genetic Vectors; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D016372:RNA, Antisense / Q000627:therapeutic use*; D012190:Retroviridae / Q000235:genetics; D015215:Zidovudine / Q000494:pharmacology
D016372:RNA, Antisense; D015215:Zidovudine