Tat has a dual role in simian immunodeficiency virus transcription

Tat has a pivotal role in human and simian immunodeficiency virus (HIV and SIV) 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...

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Bibliographic Details
Published in:	Journal of general virology 2012-10, Vol.93 (Pt 10), p.2279-2289
Main Authors:	DER VELDEN, Gisela J. Van, VINK, Monique A, BERKHOUT, Ben, DAS, Atze T
Format:	Article
Language:	eng
Subjects:	Biological and medical sciences Cells, Cultured Fundamental and applied biological sciences. Psychology Gene Expression HEK293 Cells HIV Long Terminal Repeat Human immunodeficiency virus 1 Humans Microbiology Miscellaneous Promoter Regions, Genetic RNA, Viral - genetics Simian immunodeficiency virus Simian Immunodeficiency Virus - genetics Simian Immunodeficiency Virus - metabolism tat Gene Products, Human Immunodeficiency Virus - genetics tat Gene Products, Human Immunodeficiency Virus - metabolism Trans-Activators - genetics Transcription, Genetic Virology Virus Replication - genetics
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Summary:	Tat has a pivotal role in human and simian immunodeficiency virus (HIV and SIV) 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.
ISSN:	0022-1317 1465-2099 1465-2099