Project Details

Description

The goal of this research is to understand the mechanisms whereby the Tat
protein and TAR element of human immunodeficiency virus (HIV-1) affect
viral gene expression, and how these moieties contribute to viral
pathogenicity. Tat interacts with transcripts of the TAR region to
transactivate expression of genes linked to the HIV-1 long terminal repeat
(LTR). In an adenovirus-derived model system, we have shown that this
transactivation is bi-modal: transcriptional initiation and the
processivity of RNA polymerase are both increased. The elongation effect
predominates when the basal rate of transcriptional initiation at the HIV-1
LTR is elevated, either by general transactivators with which Tat
synergizes in the adenovirus system, or by other genetic elements such as
the SV40 replication origin in a transient expression system employing
replicating plasmids. We propose to extend these findings to cell types that reflect the normal
hosts for HIV-1 infection, as well as proviral cell lines, and to analyze
the mechanism of transactivation by Tat in greater depth. Mechanistic
studies will be pursued in vivo and in a cell-free transcription system in
vitro. We will explore the roles played in Tat-transactivation by LTR
elements other than TAR, and investigate the influence of the SV40 origin
of DNA replication on transcription from the HIV LTR. Finally, we will
address the possibility that transcripts of the TAR region affect
translational efficiency and will examine the mechanisms underlying this
effect.
StatusFinished
Effective start/end date2/1/923/31/03

Funding

  • National Institutes of Health: $278,326.00
  • National Institutes of Health
  • National Institutes of Health: $325,455.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $316,057.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $291,477.00
  • National Institutes of Health

ASJC

  • Medicine(all)
  • Immunology and Microbiology(all)

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