INTRACELLULAR EXPRESSION OF MULTIMERIZED ANTISENSE TAR-CORE RNAS INHIBIT THE REPLICATION OF HUMAN IMMUNODEFICIENCY VIRUS TYPE 1 IN HUMAN CD4+T LYMPHOCYTES
- Author:
Longchuan BAI
1
;
Jiangang YUAN
;
Guangwei DU
;
Quanbi ZHAO
;
Yiming SHAO
;
Boqin QIANG
Author Information
1. Institute of Basic Medical Sciences
- Keywords:
Human immunodeficiency virus type 1(HIV-1);
TAR;
Tat;
gene therapy
- From:
Chinese Medical Sciences Journal
1999;(1):13-16
- CountryChina
- Language:Chinese
-
Abstract:
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-1SF33 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.