FELINE IMMUNODEFICIENCY VIRUS GENE EXPRESSION

Project: Research project

Project Details

Description

Feline immunodeficiency virus (FIV) is a lymphocytopathic
lentivirus associated with fatal immunodeficiency in cats. We have
molecularly cloned a biologically active provirus and are in the
process of determining the complete DNA sequence of this clone.
A major objective of the proposed research is to elucidate
molecular mechanisms regulating FIV gene expression in tissue
culture systems. The hypothesis is that cell activation and
proliferation signals are important factors regulating FIV gene
expression and replication. FIV mRNA species will be identified in productively infected feline
cell lines. Characterization of FIV transcripts in cell lines will
provide a basis for analyzing the time-course of viral RNA
synthesis and for elucidating the role of cellular physiology on
viral gene expression. Temporal regulation of FIV transcription
will be studied by analyzing synthesis of viral DNA, RNA, and
polypeptides at various times after acute infection of feline cell
lines. Transient expression assays will be used to determined
whether or not FIV encodes genes that regulate (i.e.,
transactivate) viral gene expression. Cis-acting elements
(targets) in the FIV genome that control viral gene expression will
be localized. The role of cell proliferation on FIV replication
and gene expression will be investigated in proliferating and
resting feline cell lines. Cellular factors regulating FIV
transcription will be identified. Patterns of FIV transcripts and
polypeptides will be studied at various times after infection of
activated feline T-lymphocytes and monocytes/macrophages. The
extent of FIV replication and gene expression in cultures of
resting (quiescent) T-lymphocytes will be analyzed and compared to
that in activated cells. Information from these investigations on molecular aspects of FIV
gene expression may be significant for understanding viral latency
(or low-level persistent infection). In addition, these studies
will lay a basis for elucidating viral determinants of
pathogenesis; selected mutant viruses with modifications in cis-
acting elements and trans-acting genes can be inoculated into cats
to evaluate level of viremia, tissue distribution, and pathogenic
potential. Results obtained from the proposed studies on FIV
regulation will be compared with those on other lentiviruses
including HIV and SIV. The FIV system may offer opportunities as
an animal model to relate basic mechanisms regulating lentiviral
gene expression with pathogenesis.
StatusFinished
Effective start/end date7/1/896/30/94

Funding

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

ASJC

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

Fingerprint

Explore the research topics touched on by this project. These labels are generated based on the underlying awards/grants. Together they form a unique fingerprint.