Project: Research project

Project Details


Human immunodeficiency virus (HIV), a cytopathic T-cell
lymphotropic retrovirus, is the causative agent of the acquired
immunodeficiency syndrome (AIDS). This proposal is directed at
obtaining a comprehensive understanding of the molecular
mechanisms which regulate HIV gene expression directed by the
large terminal repeat (LTR). Features characteristic of some
eucaryotic promoters have been ascribed to the HIV LTR: these
include a TATA box, an enhancer element, and sites for binding
the factor SP1. Evidence for a negative regulatory element has
also been presented. The product of a gene encoded by HIV, the
transactivator (TAT), has been shown to activate expression from
the LTR. In addition, the genes of several DNA viruses (herpes
viruses and adenovirus) transactivate expression from the HIV
LTR. The mechanisms by which these transactivations occur and
the relationship to virus latency remain to be elucidated. Specific Aim 1: Cis-acting elements in the HIV LTR regulating
viral gene expression will be defined by analyzing the
consequences of specific mutations in the LTR. Specific Aim 2: The mechanism(s) of trans-acting factors
regulating LTR-directed viral gene expression will be
investigated; interactions of binding factors with specific
sequences in the LTR will be directly analyzed. Specific Aim 3: The relationship of regulation of HIV gene
expression (directed by the LTR) to viral pathogenesis will be
investigated by (1) determining the consequences of mutations in
the LTR on virus replication and cytopathology in tissue culture
systems, (2) examining natural virus variants which differ in the
extent of cytopathic effects in tissue culture cells, and (3)
evaluating the affects of HIV infection on expression of cellular
genes. Specific Aim 4: The affects of growth conditions and physiology
of lymphoid cells on LTR-regulated gene expression will be
Effective start/end date9/15/878/31/90


  • National Institutes of Health


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


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