DETECTION OF VIRAL TRANSACTIVATORS IN PRIMARY CELLS

Project Details

Description

An association between a virus and a specific human disease can be
suggested by 1) the use of electron microscopy to visualize a virus in
pathological tissue; 2) the presence of a characteristic viral pathological
effect; 3) the presence of viral nucleic acid sequences in the diseased
cells; 4) the presence of viral antigens in malignant cells; 5) the
prevalence of the disease in patients with serologic evidence of infection
with the virus or 6) the detection of a unique viral biological activity,
such as reverse transcriptase, in pathological samples. The application of
any of these techniques to the detection of viruses associated with human
malignancies requires information about the structure, antigenic
composition, or nucleic acid sequence of the specific virus being screened
for. This application proposes the use of a novel assay that detects a
biological activity common to many transforming viruses. Conceivably, a
broad spectrum of viruses can be detected by this assay in the absence of
any specific structural or nucleic acid sequence information. This may
facilitate the detection of as yet uncharacterized viruses present in human
malignancies. The transforming genes of a broad spectrum of viruses including
adenoviruses. SV40, papilloma viruses and HTLV-I encode a transcriptional
transactivator. Although these transactivators have no structural
homologies with each other there appears to be a functional homology in
that they are all capable of transactivating genes containing an adenovirus
early promoter. Other viruses known to encode transactivators include
pseudorabies virus, other herpesviruses such as HSV and EBV, and HIV. The
pseudorabies virus transactivator shares this functional homology with the
other viruses whereas the HIV transactivator does not. Additional studies
are necessary to determine to what extent the multiple EBV transactivators
can regulate expression from the adenovirus early promoters. The experiments proposed in this application are designed to detect the
presence of a broad spectrum of viral transactivators in primary cells from
patients with a variety of diseases. The hypothesis to be tested is that
the presence of any of a broad spectrum of viruses present in these cells
will be manifested by the presence of transactivator activity as measured
by expression of marker genes linked to an adenovirus early promoter. Preliminary evidence will be presented that indicates that malignant cells
from patients with Sezary syndrome, a T cell leukemia, efficiently express
marker genes linked to an adenovirus early promoter. The similarities
between Sezary syndrome and HTLV-I related leukemia provide an impetus to
further characterize these cells and isolate the genes responsible for the
transactivation of the adenovirus early promoter. The experiments proposed
in the application are designed to extend these observations to other
diseases and to detect and ultimately isolate as yet uncharacterized
viruses which are associated with human diseases.
StatusFinished
Effective start/end date6/1/915/31/95

Funding

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

ASJC

  • Medicine(all)

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