# STRUCTURE AND FUNCTION OF ADENOVIRUS GENOME

> **NIH NIH R01** · NORTHWESTERN UNIVERSITY · 1993 · $221,408

## Abstract

There are two important sets of human adenovirus (Ad) type of 5
gene products whose functions in Ad growth cycle are either not
known or only partially understood.  These are the two
polypeptides encoded by the early gene L1, at 30.0 to 39.0 map
units and the two virus encoded small RNA genes, VAI and VAII.
In hopes that specific understanding of the precise function of
these viral products will shed light on both the process of
adenoviral infection, and on normal cellular defenses against
viruses, the following experiments are planned.

1.  To investigate the L1 gene, and Ad5 mutant with a defective
L1 gene will be constructed and propagated.  Because it is
anticipated that this mutant will be defective, a suitable trans
complementing helper system will be developed.  The phenotype of
the mutant will then be analyzed to determine the L1 gene
function(s).

2.  To define the precise mechanism action of the VA RNAs, our
present studies on VA RNA-mediated translational control in Ad
infected human and monkey cells will be continued along several
lines:

(a) To define the mechanism by which the VAI RNA blocks the
activation of eIF-2 alpha kinase in virus infected cells, host
proteins (the known dsRNA dependent kinase and/or other host
proteins) which bind to VAI RNA will be indentified.  Interaction
of these host proteins with WT and mutant VAI RNAs will be
examined to determine how interaction with the viral small RNAs
affects their function.  For kinase studies, an antibody to this
protein will be raised and the gene for the protein will be
cloned.  The kinase cDNA will be expressed in lambda gt11.  If
such proteins retain biologic activity, genetic approaches will
be used to construct a structure-function map of the kinase.

(b) To determine precisely the sequence elements and structures
of
VAI molecule that are critical for translation control, Ad5
mutants with single base substitutions in defined regions of the
VAI RNA will be generated and analyzed in vivo for translation
defect and in vitro for interaction with the host factors.

(c) This laboratory recently showed that the SV40 virus can
substitute for the VA RNA function in monkey cells if these cells
are preinfected with SV40.  The viral genome will be dissected
genetically to determine which of the SV40 genes is responsible
for this unusual complementation between different DNA viruses.
The biochemical basis of this complementation will be determined.

(d) To find out if the VAII RNA can fully substitute for the VAI
RNA, a VAI mutant which contains multiple copies of the VAII will
be constructed and analysed.

## Key facts

- **NIH application ID:** 3127647
- **Project number:** 5R01AI018029-11
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **SAM.gov UEI:** KG76WYENL5K1
- **Principal Investigator:** BAYAR THIMMAPAYA
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $221,408
- **Award type:** 5
- **Project period:** 1981-07-01 → 1994-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3127647

## Citation

> US National Institutes of Health, RePORTER application 3127647, STRUCTURE AND FUNCTION OF ADENOVIRUS GENOME (5R01AI018029-11). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3127647. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*