# NEURAL CELLS PERSISTENTLY INFECTED WITH SV40, BKV OR JCV

> **NIH NIH R01** · UNIVERSITY OF MASSACHUSETTS AMHERST · 1989 · $112,617

## Abstract

The goal of this proposal is to advance our understanding of papovaviral
persistent infection in general and, to elucidate those processes which
might underlie papovaviral persistence and pathogenesis in the human slow
virus disease, progressive multifocal leukoencephalopathy (PML).  Because
this neurodegenerative disease is the only human illness in which
papovaviruses are clearly implicated, we also seek to identify those
factors which might predispose the central nervous system to papovaviral
persistence or, more likely, to chronic disease.

Toward these ends we will evaluate basic parameters of simian virus 40
(SV4Q), BK virus, and JC virus (the primary etiologic agent of PML)
persistent infections established in cultures of human neuroblastoma and
glioblastoma cell lines, in explants of human oligodendrogliomas, and in
cell cultures of non-neural origin.  We will determine the proportion of
cells which either produce virus, or which support only limited viral gene
expression, or which contain completely latent viral genomes.  We will
assess the temporal relationship between viral replication and cell
killing.  We will determine the states of the viral genomes (e.g.
integrated versus free, defective versus nondefective) in latently infected
clonal isolates and assess whether there is a relationship between those
states and the probability of reactivation of the productive infection.  We
will analyze viral variants which might emerge, particularly with respect
to their capacities to modulate the productive infection.  We will evaluate
cellular factors which might act to regulate the infection and we will
determine whether those factors are related to the physiological state of
the cells or to their level of differentiation.

To advance our understanding of the PML disease process we will determine
if persistent infection leads to specific impairment of the specialized
functions expressed by the neuronal-like and glial-like cell cultures.
Specialized functions to be examined include enzyme activities of
neurotransmitter metabolism, neurotransmitter receptor functions,
electrophysiological activity, and the expression by glial cells of
extrinsic influences which promote and maintain the functional competence
of neuronal cells.

## Key facts

- **NIH application ID:** 3125622
- **Project number:** 3R01AI014049-10S1
- **Recipient organization:** UNIVERSITY OF MASSACHUSETTS AMHERST
- **SAM.gov UEI:** VGJHK59NMPK9
- **Principal Investigator:** Leonard C. Norkin
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1989
- **Award amount:** $112,617
- **Award type:** 3
- **Project period:** 1977-09-01 → 1990-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3125622

## Citation

> US National Institutes of Health, RePORTER application 3125622, NEURAL CELLS PERSISTENTLY INFECTED WITH SV40, BKV OR JCV (3R01AI014049-10S1). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3125622. Licensed CC0.

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