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Journal of Virology, October 2000, p. 9206-9213, Vol. 74, No. 19
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

Jayasri Das Sarma,1 Li Fu,1 Jean C. Tsai,2 Susan R. Weiss,2 and Ehud Lavi1,*

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.

* 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.

Journal of Virology, October 2000, p. 9206-9213, Vol. 74, No. 19
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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