Tat has a dual role in simian immunodeficiency virus transcription

被引:7
作者
van der Velden, Gisela J. [1 ]
Vink, Monique A. [1 ]
Berkhout, Ben [1 ]
Das, Atze T. [1 ]
机构
[1] Univ Amsterdam, Lab Expt Virol, Dept Med Microbiol, Ctr Infect & Immun Amsterdam CINIMA,Acad Med Ctr, NL-1012 WX Amsterdam, Netherlands
关键词
HIV-1 REVERSE TRANSCRIPTION; REGULATED GENE-EXPRESSION; SP1; BINDING-ELEMENTS; NF-KAPPA-B; TYPE-1; REPLICATION; VIRAL REPLICATION; TERMINAL DOMAIN; MESSENGER-RNA; PROTEIN; ACTIVATION;
D O I
10.1099/vir.0.044511-0
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Tat has a pivotal role in human and simian immunodeficiency virus (HIV and Sly) replication because it stimulates transcription by binding to the trans-activator response (TAR) element. In addition, several other Tat functions have been proposed. Most studies have focused on HIV-1 Tat and much less is known about SIV Tat. An SIVmac239 variant was constructed previously in which the Tat-TAR transcription mechanism is functionally replaced by the doxycycline-inducible Tet-On gene expression mechanism (SIV-rtTA). In this study, SIV-rtTA variants were used to analyse the functions of SIV Tat. It was shown that Tat-minus SIV-rtTA variants replicated efficiently in PM1 T-cells, ruling out an additional essential Tat function. Nevertheless, replication was suboptimal in other cells, and evolutionary pressure to repair Tat expression was documented. It was demonstrated that SIV-rtTA required Tat for optimal gene expression, despite the absence of the Tat-TAR axis. This Tat effect was lost upon replacement of the long terminal repeat promoter region by a non-related promoter. These results indicate that Tat can activate SIV transcription via TAR RNA and U3 DNA elements but has no other essential function in replication in cultured cells. The experiments were limited to cell lines and PBMCs, and did not exclude an accessory Tat function under specific conditions or in vivo.
引用
收藏
页码:2279 / 2289
页数:11
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