Intracellular expression of multimerized antisense TAR-Core RNAs inhibit the replication of human immunodeficiency virus type 1 in human CD4+ T lymphocytes.
Gene therapy is one of several approaches that are being tested in the search for an effective anti-HIV treatment. In this strategy, a "resistant" gene would be introduced into target cells, rendering them resistance to the infection of HIV. The HIV-1 Tat protein transactivate HIV-1 gene expression at the transcriptional level by interacting with its response element (TAR) in the long terminal repeat (LTR). Previously, we have shown that antisense polyTAR-Core RNAs can inhibit the transactivation of HIV-1 Tat protein in transiently transfected Jurkat cells. To determine whether this antisense polyTAR-Core RNAs could inhibit HIV-1 replication in CD4+ T cells, we transfected the antisense polyTAR-Core gene to MT4 cells and challenged them with HIV-1 SF33 strain. Levels of HIV-1 p24gag antigen were reduced more than 4-fold in cultures of the transduced MT4/LR cells infected with HIV-1 SF33 strain. In contrast, cultures of nontransduced MT4 cells and control LX vector transduced MT4/LX cells infected with the same viruses had high levels of HIV-1 p24gag. Our work showed that antisense polyTAR-Core RNAs were able to inhibit HIV-1 replication in CD4+ T cells, and could be used as resistance gene in further studying for gene therapy against HIV-1.
Longchuan
B
B
National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, CAMS & PUMC, Beijing 100005.
Jiangang
Y
Y
Guangwei
D
D
Quanbi
Z
Z
Yiming
S
S
Boqin
Q
Q
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000378:metabolism; D002460:Cell Line; D015316:Genetic Therapy; D005822:Genetic Vectors; D016325:HIV Long Terminal Repeat / Q000235:genetics*; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D016372:RNA, Antisense / Q000096:biosynthesis*; D012367:RNA, Viral / Q000235:genetics; D012190:Retroviridae / Q000235:genetics; D014162:Transfection; D014779:Virus Replication / Q000187:drug effects
D016372:RNA, Antisense; D012367:RNA, Viral