Tat has a dual role in simian immunodeficiency virus transcription

G.J. van der Velden, M. Vink, B. Berkhout, A.T. Das

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

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.
Original languageEnglish
Pages (from-to)2279-2289
Number of pages11
JournalJournal of General Virology
Volume93
Issue numberPt 10
Publication statusPublished - 18 Jul 2012
Externally publishedYes

Keywords

  • Econometric and Statistical Methods: General
  • Geneeskunde(GENK)
  • Medical sciences
  • Bescherming en bevordering van de menselijke gezondheid

Fingerprint

Dive into the research topics of 'Tat has a dual role in simian immunodeficiency virus transcription'. Together they form a unique fingerprint.

Cite this