Functional domains of tat required for efficient human immunodeficiency virus type 1 reverse transcription

被引:40
|
作者
Ulich, C
Dunne, A
Parry, E
Hooker, CW
Gaynor, RB
Harrich, D
机构
[1] Royal Childrens Hosp, Sir Albert Sakzewski Virus Res Ctr, Natl Ctr HIV Virol Res, HIV Res Unit, Herston, Qld 4029, Australia
[2] Univ Texas, SW Med Ctr, Dept Internal Med, Div Hematol & Oncol, Dallas, TX 75235 USA
[3] Univ Texas, SW Med Ctr, Dept Microbiol, Dallas, TX 75235 USA
关键词
D O I
10.1128/JVI.73.3.2499-2508.1999
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Tat expression is required for efficient human immunodeficiency virus type 1 (HIV-1) reverse transcription. In the present study, we generated a series of 293 cell lines that contained a provirus with a tat gene deletion (Delta tat). Cell lines that contained Delta tat and stably transfected vectors containing either wild-type tat or a number of tat mutants were obtained so that the abilities of these tat genes to stimulate HIV-1 gene expression and reverse transcription could be compared. tat genes with mutations in the amino terminus did not stimulate either viral gene expression or HIV-1 reverse transcription. In contrast, tat mutants in the activation, core, and basic domains of Tat did not stimulate HIV-1 gene expression but markedly stimulated HIV-1 reverse transcription. No differences in the levels of virion genomic RNA or tRNA(3)(Lys) were seen in the HIV-1 Delta tat viruses complemented with either mutant or wild type tat. Finally, overexpression of the Tat-associated kinases CDK7 and CDK9, which are involved in Tat activation of HIV-1 transcription, was not able to complement the reverse transcription defects associated with the lack of a functional tat gene. These results indicate that the mechanism by which tat modulates HIV-1 reverse transcription is distinct from its ability to activate HIV-1 gene expression.
引用
收藏
页码:2499 / 2508
页数:10
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