# MOLECULAR APPROACH TO THE UNIQUE BIOLOGY OF JC VIRUS

> **NIH NIH R01** · PENNSYLVANIA STATE UNIVERSITY, THE · 1992 · $122,324

## Abstract

Exposure to JC Virus (JCV) usually usually occurs during childhood
and generally results in a subclinical infection.  The virus may
persist for life in the kidneys, however in immunocompromised
individuals JCV may reach the brain and cause the fatal
demyelinating disease PML.  In addition to its pathogenic potential
in people, JCV has proven to a highly oncogenic in animals;
inoculation of JCV into rodents and primates results in a variety
of tumors, some of which are among the more frequent types in
humans.

In contrast to its efficient activity in vivo, JCV exhibits
restricted lytic and transforming activities in vitro.  Our recent
studies indicate that while both regulatory and T antigen coding
sequences contribute to this restricted behavior, the latter
sequences play a greater role.  Our long term objective is to
identify those sequences within the early coding region that
contribute to the unique biology of JCV.  To achieve this goal, our
specific aims will revolve around three experimental approaches:

1) Analysis of chimeric viruses that utilize homologous and
heterologous regulatory signals to express hybrid T proteins.  JCV,
BKV, and SV40 differ significantly in their lytic and transforming
abilities; can domains of the JCV T antigen be identified that are
responsible for JCV's restricted phenotype in vitro?  Does the
creation of transgenic mice harboring hybrid vs parental viral
genomes allow us to identify sequences involved in tumorigenic and
pathologic potential?

2) Wild type JCv T protein - overexpression in adenovirus vectors,
purification by affinity chromatography, and characterization via
biochemical/functional assays.  Polyomavirus T antigens are
multifunctional proteins that play various roles in DNA
replication, transcription" and oncogenicity.  Various regions of
the SV40 and Polyoma T proteins are associated with specific
functions; are differences in functional domains of JCV T
responsible for biological differences between these related
viruses?  The availability of hybrid and mutant T proteins for
similar analyses will enhance these studies.

3) Mutational analysis of the JCV T protein.  Mutations will be
introduced into the JCV early coding sequences at sites considered
to be interesting based on our sequence analysis of wild type and
mutant SV40 T proteins.  Random and specific mutagenesis be used
JCV does conversion of a JCV T to an SV40-like T enhance the lytic
and transforming capabilities of JCV in vitro?

## Key facts

- **NIH application ID:** 3177078
- **Project number:** 5R01CA038789-08
- **Recipient organization:** PENNSYLVANIA STATE UNIVERSITY, THE
- **SAM.gov UEI:** NPM2J7MSCF61
- **Principal Investigator:** RICHARD John FRISQUE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1992
- **Award amount:** $122,324
- **Award type:** 5
- **Project period:** 1984-12-01 → 1993-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3177078

## Citation

> US National Institutes of Health, RePORTER application 3177078, MOLECULAR APPROACH TO THE UNIQUE BIOLOGY OF JC VIRUS (5R01CA038789-08). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3177078. Licensed CC0.

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