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Journal of Virology, October 2000, p. 9206-9213, Vol. 74, No. 19
Division of Neuropathology, Department of
Pathology and Laboratory Medicine,1 and
Department of Microbiology,2 School of
Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104
Received 19 April 2000/Accepted 20 June 2000
Demyelination is the pathologic hallmark of the human
immune-mediated neurologic disease multiple sclerosis, which may be triggered or exacerbated by viral infections. Several experimental animal models have been developed to study the mechanism of
virus-induced demyelination, including coronavirus mouse hepatitis
virus (MHV) infection in mice. The envelope spike (S) glycoprotein of
MHV contains determinants of properties essential for virus-host
interactions. However, the molecular determinants of MHV-induced
demyelination are still unknown. To investigate the mechanism of
MHV-induced demyelination, we examined whether the S gene of MHV
contains determinants of demyelination and whether demyelination is
linked to viral persistence. Using targeted RNA recombination, we
replaced the S gene of a demyelinating virus (MHV-A59) with the S gene of a closely related, nondemyelinating virus (MHV-2). Recombinant viruses containing an S gene derived from MHV-2 in an MHV-A59 background (Penn98-1 and Penn98-2) exhibited a persistence-positive, demyelination-negative phenotype. Thus, determinants of demyelination map to the S gene of MHV. Furthermore, viral persistence is
insufficient to induce demyelination, although it may be a prerequisite
for the development of demyelination.
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Demyelination Determinants Map to the Spike
Glycoprotein Gene of Coronavirus Mouse Hepatitis Virus
*
Corresponding author. Mailing address: University of
Pennsylvania, School of Medicine, Division of Neuropathology,
Department of Pathology and Laboratory Medicine, 613 Stellar-Chance
Building, Philadelphia, PA 19104-6100. Phone: (215) 898-8198. Fax:
(215) 898-9969. E-mail: lavi{at}mail.med.upenn.edu.
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