ROLE OF NOVEL X-REGION PROTEINS IN HTLV-1/11

Project: Research project

Description

The leukemogenic retroviruses, HTLV-I and HTLV-II, have been
linked to specific lymphoid malignancies in man. Extensive
recent studies have focused on the protein product of a new gene,
termed the HTLV Chi gene (also referred to as lor, Chi-lor, and
tat-I/II) found in both viruses. This gene has been shown to be
involved in transcriptional regulation of viral expression, and thus
critical for viral replication. More recently, another protein has
been shown to be encoded by the Chi gene mRNA. This protein is
encoded from an overlapping reading frame for that of the trans-
activating protein. The highly basic nature of this new protein
and its nuclear localization suggest a role for this protein in
regulation of viral gene expression. Preliminary studies indicate that loss of function of this new
protein results in a reduction of transcriptional activation of the
HTLV Chi gene, even is the trans-activating protein of HTLV-II,
p37 Chi II, is unaffected. Based upon these initial studies, we will
determine whether the new protein, termed pX-b, is involved in
the trans-activating process of HTLV, and whether its acts at a
transcriptional or post-transcriptional level. In addition, I will
generate complete viral genomes which specifically lack the gene
encoding pX-B, and determine the phenotype of the mutant viral
genomes with respect to replication and transformation. As yet, the mechanism of transformation by HTLV is unknown.
Characterization of the newly identified protein encoded by the
Chi gene is critical to understanding how HTLV-I and HTLV-II
transform T cells in vitro and cause leukemia in man.
StatusFinished
Effective start/end date8/17/876/30/92

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health

Fingerprint

Human T-lymphotropic virus 1
Human T-lymphotropic virus 2
Proteins
Genes
Reading Frames
Viral Genome
Viral Proteins
Retroviridae
Transcriptional Activation
Leukemia
Viruses
T-Lymphocytes
Phenotype
Gene Expression
Messenger RNA

ASJC

  • Medicine(all)