# CORONAVIRUSES: MOLECULAR BIOLOGY AND PERSISTENCE

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 1988 · $142,428

## Abstract

The long term goal of this project is to understand the molecular basis of
some of the biological properties of the murine coronavirus, mouse
hepatitis virus (HMV).  Some strains of MHV cause persistent demyelinating
disease in the central nervous system (CNS) of mice.  This infection has
been cited as a model for the human disease Multiple Sclerosis.  MHV also
readily establishes persistent infections in cultured cells.  Thus, MHV
presents a model system for the study of viral persistence, tissue tropism,
and virus-induced demyelination.  We propose to undertake a detailed
analysis of the molecular biology of replication of this virus and then use
this information to start to ask questions about the molecular basis of
persistence and neurotropism.

Molecular Studies:  The sequences of the intergenic regions flanking the E1
and N genes (at the 3 prime end of the MHV-A59 genome) will be obtained by
sequencing of cDNA clones.  A comparison of these intergenic sequences with
sequences on the 5 prime ends of the corresponding mRNAs will bear on the
mechanism of synthesis of the subgenomic mRNAs.  Negative strand RNA,
presumably an intermediate in the replication of genome and transcription
of mRNAs will be characterized as to size, kinetics of accumulation,
association with positive strand RNA.  The sequences at the termini of
negative strand RNA will be compared to the terminal sequences of genome
RNA to look for putative RNA polymerase initiation sites for replication.
Sequence information will be obtained for regions 5 prime to the N and E1
genes by stepwise cDNA cloning across the genome.  As a long term goal we
plan to clone the entire genome and generate sequences for the genes
involved in tropism and persistence.

Biological Studies:  We will use the information obtained above as well as
the reagents generated to start to address the biological questions.
Persistently infected cells as well as CNS samples from persistently
infected mice will be analyzed with a focus on changes in viral genome
expression associated with persistence.  DNA probes homologous to human and
murine coronaviruses will be used to probe for viral sequences in human
tissues from MS, hepatitis and enteric disease patients.

## Key facts

- **NIH application ID:** 3127222
- **Project number:** 5R01AI017418-08
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **SAM.gov UEI:** GM1XX56LEP58
- **Principal Investigator:** Susan R Weiss
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $142,428
- **Award type:** 5
- **Project period:** 1981-01-01 → 1989-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3127222

## Citation

> US National Institutes of Health, RePORTER application 3127222, CORONAVIRUSES: MOLECULAR BIOLOGY AND PERSISTENCE (5R01AI017418-08). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3127222. Licensed CC0.

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