REGULATION OF SIMIAN FOAMY VIRUS GENE EXPRESSION

Project: Research project

Description

The foamy viruses, or syncytium-forming viruses, are members of the
spumaviriniae sub-family of retroviruses. Foamy viruses are found in
many mammalian species and appear to be non-pathogenic in their natural
hosts even though they have a wide tissue range and induce extensive
cytopathology in cell cultures. The genomes of simian foamy virus type 1
(SFV-l) from rhesus macaque and human spumaretrovirus (HSRV) have been
molecularly cloned and sequenced; pairwise comparisons of these two
viruses show from 30% to 80% homology, depending on the region selected
for analysis. Both viruses encode several open reading frames (ORFs) in
addition to genes for virion structural proteins. Recent studies have
revealed that SFV-1 and HSRV each encode a transactivator (taf) which
functions to strongly augment transcription directed by the viral long
terminal repeat (LTR). The main objective of this proposal is to
elucidate molecular mechanisms regulating SFV-1 gene expression directed
by the viral LTR. It remains to be determined whether taf acts directly
on the LTR or whether transactivation is mediated by cellular factors.
The target (TAR) for taf is distributed over two parts of the U3 domain
of the viral LTR upstream from the TATA box in the viral promoter. Each
these two TAR regions is about 300 base pairs (bp) long and no homologies
(i.e., repeat elements) are detected between the two TARs. In addition,
the promoter-distal TAR (TAR-d) functions in only in the sense
orientation whereas the promoter-proximal TAR (TAR-p) functions in either
orientation. These observations (on the complex nature of the targets)
support the hypothesis that taf may function through more than one
cellular factor which interacts with different sequence elements in the
U3 region of the LTR. SPECIFIC AIM 1: Binding sites for cellular factors and the precise target
sequences for taf in the SFV-1 LTR will be defined. SPECIFIC AIM 2: Monospecific antibodies will be made to detect the SFV-1
taf gene product; taf protein in infected cells will be extensively
characterized. SPECIFIC AIM 3: Genetically engineered yeast and mammalian cells will be
used to produce the SFV-1 taf gene product for structural and functional
studies. SPECIFIC AIM 4: To elucidate the mechanism of SFV-1 transcriptional
transactivation, functional domains of taf will be identified by
mutagenesis and by evaluation of hybrid transactivators. These studies on SFV-1 regulation are relevant for elucidating mechanisms
which control viral latency (or persistent infection) in the host animal.
Observations made in the course of the proposed research will also
enhance the understanding of mechanisms controlling eucaryotic
transcription; the proposed studies on SFV-1 gene expression are
significant since new (cellular) transcriptional factors may be
identified.
StatusFinished
Effective start/end date7/1/924/30/97

Funding

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

Fingerprint

Simian foamy virus
Spumavirus
Trans-Activators
Gene Expression
Viruses
Virus Latency
Genes
TATA Box
Giant Cells
Retroviridae
Transcriptional Activation
Macaca mulatta
Base Pairing
Virion
Open Reading Frames
Proteins
Terminal Repeat Sequences
Cell Culture Techniques
Yeasts
Binding Sites

ASJC

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