Project: Research project

Project Details


Although evolutionarily distinct, both the human T-cell leukemia viruses
types I (HTLV-I) and II (HTLV-II) and the human immunodeficiency viruses
(HIV-1, HIV-2, and SIV) have evolved analogous transacting regulatory
mechanisms which may be important in pathogenesis. The rex gene of HTLV-I
and HTLV-II, and similarly, the rev gene of HIV-1, have been shown to be
required for accumulation of unspliced gag/pol in the cytoplasm of infected
cells. In our laboratory, we wish to define the regulatory effects of Rex
in the context of HTLV-II.

1. We will study the effects of HTLV-II Rex on subcellular localization of
different viral mRNA species expressed from HTLV-II clones, effects of rex
mutations on overall mRNA levels, and mechanisms underlying positive and
negative regulatory effects of Rex on expression from the viral long
terminal repeat (LTR).

2.Cis-acting sequences responsive to Rex will be defined, and direct
binding assays employed to identify and purify cellular and/or viral
proteins which interact with Rex and/or these regions.

3. Mutagenesis in rex will be performed and correlated with effects in a
variety of functional assays to define functional domains within rex. These
include assays for nuclear/cytoplasmic levels of spliced versus unspliced
mRNA, assays for Rex effects on HTLV-II LTR-linked expression
(trans-activation), and assays for Rex-mediated rescue of HIV-1
Rev-deficient mutants.

4. The effects of Rex on cellular gene expression will be investigated,
including effects on expression of genes; specifically, trans-activated by
Tax, such as the granulocyte-macrophage colony-stimulating factor (GM-CSF)
gene, and effects on processing of other cellular mRNAs.

This proposal will address the role of Rex in viral gene regulation, in
transition from productive to latent infection, and in cellular
transformation. A better understanding of Rex may lead to advances in
treatment of retroviral infection by HTLV-I, HTLV-II, and possibly HIV-1.
Effective start/end date9/20/908/31/95


  • National Cancer Institute
  • National Cancer Institute
  • National Cancer Institute
  • National Cancer Institute


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