Demyelination determinants map to the spike glycoprotein gene of coronavirus mouse hepatitis virus.
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.
Das Sarma
J
J
Division of Neuropathology, Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia 19104, USA.
Fu
L
L
Tsai
J C
JC
Weiss
S R
SR
Lavi
E
E
D000818:Animals; D018352:Coronavirus Infections / Q000821:virology*; D003711:Demyelinating Diseases / Q000821:virology*; D015967:Gene Expression Regulation, Viral; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics*; D051379:Mice; D006517:Murine hepatitis virus / Q000235:genetics*; D064370:Spike Glycoprotein, Coronavirus; D014759:Viral Envelope Proteins / Q000235:genetics*
D008562:Membrane Glycoproteins; D064370:Spike Glycoprotein, Coronavirus; D014759:Viral Envelope Proteins