# CARDIOVIRAL PROTEASES AND COMPARATIVE GENOME STRUCTURE

> **NIH NIH R01** · UNIVERSITY OF WISCONSIN-MADISON · 1992 · $176,608

## Abstract

The medical and agricultural importance of picornavirus-caused disease
has long targeted these agents for intensive laboratory study. The
family encompasses a diverse variety of pathogenic agents, such as
polio, rhino, foot-and mouth-disease, hepatitis A, coxsackie, and the
murine cadioviruses (among others). The small size of the RNA genome
(about 8,000 bases) and the relatively simple nature of the icosametric
capsid shell have allowed facile manipulation of genomes as infectious
CDNA copies, and determination of several virion structures to atomic
resolution. These powerful tools not withstanding, there still remain
many unresolved questions about how or why a specific infection does
indeed bring about a particular course of disease within its natural
host. Central to these processes is the molecular examination of all
facets of a virus life cycle, especially those ensuing within the
infected cell. Such studies not only bring to light the (exploitable)
individualities of particular viral phenotypes, but also serve as
critical probes to the inner workings of elementary biological phenomena
whose disruption through infection can mediate the expression of
disease.

This program focuses on the murine cardioviruses, encephalomyocarditis
virus (EMCV) and Mengovirus. The special propensity of cardioviral RNAs
facilitate efficient translation in cell-free extracts, is a hallmark of
these genomes, and makes these isolates exceptionally useful
experimental subjects for molecular dissection of the pico mavirus life
cycle. The goals of this investigation are to explore and define the
relationship of the cardiovirus genus to other members of the
piconavirus family, and to exploit the unique features of cardioviruses
to examine fundamental molecular questions about piconaviral
translation, proteolytic processing and morphogenesis. The specific aims
are: (1) To define the sequence and structural contexts required for the
novel NPGP "suicide" cleavage that is responsible for primary
proteolytic processing of cardioviral polyprotein; (2) To evaluate the
in vivo effects of engineered mutations introduced into the viral 3C
protease, its processing sites, or other relevant genomic locations, and
to correlate these results with specific phases or defects in the
cardioviral life cycle; (3) To probe distinctive sequence and structural
elements within the 5' noncoding region of cardioviral RNAs, and assess
their responsibilities in cap-independent translation initiation and in
viral-induced host protein shut-off during natural infection; and (4) To
compare and contrast all available piconavirus sequence data by computer
analysis, with special emphasis of correlative support for a revised
taxonomic ordering of the family. Innovative, computer-generated graphic
displays of internal and external virion capsid surfaces will also be
advanced, for detailed molecular surface maps and topographical feature
comparisons.

## Key facts

- **NIH application ID:** 3127153
- **Project number:** 2R01AI017331-12
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **SAM.gov UEI:** LCLSJAGTNZQ7
- **Principal Investigator:** ANN C. PALMENBERG
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1992
- **Award amount:** $176,608
- **Award type:** 2
- **Project period:** 1980-12-01 → 1997-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3127153

## Citation

> US National Institutes of Health, RePORTER application 3127153, CARDIOVIRAL PROTEASES AND COMPARATIVE GENOME STRUCTURE (2R01AI017331-12). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3127153. Licensed CC0.

---

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