# CORONAVIRUS STRUCTURE AND REPLICATION

> **NIH NIH R01** · UNIVERSITY OF TENNESSEE KNOXVILLE · 1989 · $104,675

## Abstract

The long-term objectives are to understand the molecular details of
coronavirus structure and replication, especially with regard to the
function of specific gene products, and mechanisms regulating
replication during a cytopathogenic acute infection and those regulating
replication during a noncytopathogenic persistent infection.
Coronaviruses cause primarily severe to mild acute gastrointestinal and
respiratory diseases in animals and humans, and chronic multiorgan
diseases in some animals and possible humans. The specific aims of this
proposal are:  (1) To complete the sequencing of the genome of the
porcine transmissible gastroenteritis coronavirus (TGEV) (11Kb remaining
of a 20 Kb genome), a region that encodes the RNA-dependent RNA
polymerase. cDNA clones that map in this region will be sequenced by a
combination of the chemical and dideoxy methods and more cDNA clones
will be generated to close the remaining gaps. A strategy for
reconstructing a full-length (genome) cDNA will be developed in order to
generate infectious RNA transcripts.  (2) To characterize the products
of open reading frames in the genome of TGEV and the bovine enteric
coronavirus (BCV), regions that have been sequenced, with regard to
their structure, localization, and function during virus replication.
Open reading frames will be subcloned into expression vectors to
generate products in vitro and in vivo.  Antibodies will be produced to
the individual proteins and the localization and orientation of the
protein in cell organelles will be studied. The effects of stably
expressed products on virus replication will be determined.   (3) To
block expression of specific genes and RNA replication by site-directed
nucleic acid inhibition in order to analyze specific coronavirus
replicational events.  Both externally applied oligodeoxynucleotides
(and modified oligodeoxynucleotides) and internally expressed
"antisense" sequences will be studied.  Inhibition of virus replication
will be studied by blocking specific events separately in acute and
persistent infections in cell culture.

## Key facts

- **NIH application ID:** 3125713
- **Project number:** 2R01AI014367-10
- **Recipient organization:** UNIVERSITY OF TENNESSEE KNOXVILLE
- **SAM.gov UEI:** FN2YCS2YAUW3
- **Principal Investigator:** David Alvin Brian
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1989
- **Award amount:** $104,675
- **Award type:** 2
- **Project period:** 1977-07-01 → 1994-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3125713

## Citation

> US National Institutes of Health, RePORTER application 3125713, CORONAVIRUS STRUCTURE AND REPLICATION (2R01AI014367-10). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3125713. Licensed CC0.

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