Demyelination determinants map to the spike glycoprotein gene of coronavirus mouse hepatitis virus. Academic Article uri icon

Overview

abstract

  • 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.

publication date

  • October 1, 2000

Research

keywords

  • Coronavirus Infections
  • Demyelinating Diseases
  • Membrane Glycoproteins
  • Murine hepatitis virus
  • Viral Envelope Proteins

Identity

PubMed Central ID

  • PMC102119

Scopus Document Identifier

  • 0033808456

Digital Object Identifier (DOI)

  • 10.1128/jvi.74.19.9206-9213.2000

PubMed ID

  • 10982367

Additional Document Info

volume

  • 74

issue

  • 19