# ADENOVIRUS GENOME EXPRESSION:  PHYSICAL MAPPING STUDIES

> **NIH NIH R01** · VANDERBILT UNIVERSITY · 1988 · $185,936

## Abstract

The proposed research is designed to elucidate the roles of adenovirus DNA
sequences in the regulation of gene expression, DNA encapsidation and
evolutionary diversification.  Recently described autoregulation by the
adenovirus E1A gene provides a model system for the investigation.  E1A
promoter sequences, or derivative variants, have been joined to probe genes
such as chloramphenicol acetyltransferase to conveniently measure extents
of gene expression in transfected human cells in culture.  The effects of
cotransfecting wild type or mutant E1A genes on expression of the E1A-probe
is readily determined.  Evidence indicates negative autorepression and two
modes of positive feedback in E1A autoregulation.  These assays will be
used to localize cis-targets for promoter response to E1A and functional
domains within the E1A peptide(s).  A cis-element specifying polar DNA
encapsidation lies within the transcriptional control region of the E1A
gene and this will be further characterized.

The adenovirus E1A is one of the two adenovirus genes involved in the
process of adenovirus induced oncogenic transformation of cells.  The
tumorigenicity of adenoviruses is also related to the E1A gene, in a
fashion which varies with the particular subgroup of human adenovirus
serotypes.  This enhances interest in the regulatory properties and
evolution of the adenovirus E1A gene.

The B subgroup of human adenoviruses, moderately oncogenic, is comprised of
two closely related but epidemiologically and pathogenically distinct clans
or sub-subgroups.  The B1 viruses can cause serious epidemic respiratory
disease while the B2 viruses are generally recovered from asymptomatic
patients subject to immunosuppression.  DNA sequence analysis of the E1A
and fiber genes will be performed for representative serotypes of each
sub-subgroup to characterize their phylogeny and evolutionary constraints
on regulatory and structural genes.  This may provide further insights on
the functional domains within the genes and their fate through evolution.

Sequences from B and C subgroup adenoviruses will be cloned into bacterial
expression vectors and screened using sera from individuals having been
infected or vaccinated with specific adenoviruses.  Immunopositive clones
will be mapped by hybridization and DNA sequence to the respective viral
genomes to identify DNA sequences which encode antigenic determinants.
This background will be useful in the further efforts to develop a
practical adenovirus vaccine vector.

## Key facts

- **NIH application ID:** 3171875
- **Project number:** 5R01CA034126-06
- **Recipient organization:** VANDERBILT UNIVERSITY
- **SAM.gov UEI:** GTNBNWXJ12D5
- **Principal Investigator:** Clark Tibbetts
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $185,936
- **Award type:** 5
- **Project period:** 1982-07-01 → 1991-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3171875

## Citation

> US National Institutes of Health, RePORTER application 3171875, ADENOVIRUS GENOME EXPRESSION:  PHYSICAL MAPPING STUDIES (5R01CA034126-06). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3171875. Licensed CC0.

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