# VIRAL INTERFERENCE IN CARRIER CULTURES

> **NIH NIH R01** · ALLEGHENY UNIVERSITY OF HEALTH SCIENCES · 1992 · $234,564

## Abstract

The role that cellular receptors serve as determinants of
coxsackievirus tropism in the pathogenesis of human and animal
diseases continues to be the long range goal of this program.  The
HeLa cell receptor (HR1) for the coxsackieviruses of group B (CB)
has been purified in a detergent-stable complex with virions.  A
second receptor (HR2) for binding the CB-RD variant viruses to
RD cells and to HeLA cells has been discovered.  Purification
methods other than that used for HR1 must be developed due to
the labile nature of the CB-RD variants.  Assays with monoclonal
antibodies, reveals that the HeLa cell RD-virus receptor (HR2) is
not functional (does not bring the virus into the infectious
pathway), while the receptor (HR2) on RD cells is fully active.
We plan to look for structural differences between the HR2
receptors on RD and HeLa cells which may be required for
biological activity.  "Probes" are needed for characterization,
isolation and quantitation of receptors, and for cDNA cloning.
Additional receptor-specific monoclonal antibodies are being
produced.  Adenovirus fiber protein which also specifically binds
to both human and mouse receptors for the group B
coxsackieviruses will serve as another probe.  We have begun to
use these probes in attempts to clone the HeLa cell HR1 receptor
in a lambda gt11 expression vector.  The amino acid sequence of
the coxsackievirus receptors will be predicted from the cDNA
sequences.  We will also attempt to use human DNA probes for
identification of mouse cDNA clones.  Expression of functional
receptors in either bacterial or eucaryotic systems may provide
larger amounts of the receptor proteins for purifiction and use in
biochemical study of virus-receptor interaction, and also for
preparation of specific high titer antibody.  One of the goals is
the characterization of the virus-receptor complex by X-ray
crystallography (collaboration with M. Rossman at Purdue).  The
contribution of the receptor to the process of viral uncoating will
also be investigated.  In addition, the relationship between the
distribution and activity of host cell receptors in inbred mice in
the development of viral pathogenesis will be investigated.  DNA
probes for receptor mRNA and antibodies to receptors will allow
mapping of receptor distribution in organs and cells.  Sites of
virus multiplication will be determined by titration of infectivity,
by immunohistochemistry, and by in situ hybridization using DNA
or RNA probes for viral RNA.  These results will be correlated
with the known patterns of coxsackievirus pathogenesis.

## Key facts

- **NIH application ID:** 3124148
- **Project number:** 5R01AI003771-31
- **Recipient organization:** ALLEGHENY UNIVERSITY OF HEALTH SCIENCES
- **Principal Investigator:** RICHARD L CROWELL
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1992
- **Award amount:** $234,564
- **Award type:** 5
- **Project period:** 1975-05-01 → 1994-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3124148

## Citation

> US National Institutes of Health, RePORTER application 3124148, VIRAL INTERFERENCE IN CARRIER CULTURES (5R01AI003771-31). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3124148. Licensed CC0.

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