Characterization of coronavirus JHM variants isolated from wistar furth rats with a viral-induced demyelinating disease

Abstract

Murine hepatitis virus (MHV) can cause neurological disease when inoculated intracerebrally (ic) into mice and rats. Specifically the JHM strain of MHV (MHV-JHM) generally causes an acute encephalitis when inoculated ic into 2-day-old Wistar Furth rats. In contrast, JHM generally produces a chronic demyelinating disease with resulting posterior paralysis when inoculated ic into 10-day-old Wistar Furth rats. In addition, while JHM readily produces a productive infection in a mouse fibroblast cell line (L-2), it does not form syncytia or replicate well in a tissue cell line of glial origin (G26-24). We have isolated and characterized three MHV-JHM viral variants from the central nervous system of two Wistar Furth rats with a MHV-JHM-induced demyelinating disease. The pattern of viral-specific mRNA for all three of these variants differed from what was observed for the wild-type parental MHV-JHM that had been passaged only in tissue culture. One of these variants, ATllf cord virus, which induced a chronic demyelinating disease in 2- or 10-day-old intracerebrally inoculated Wistar Furth rats, had a deletion in the coding region of the peplomer glycoprotein mRNA. In addition, this variant formed massive syncytia and replicated well in G26-24 cells. We have not detected this deletion in the other two JHM variants, ATllf brain virus and ATlle brain virus. ATllf brain virus and ATlle brain virus primarily produced an acute encephalitis when reinoculated into 2- or 10-day-old Wistar Furth rats. In addition, these two variants did not form syncytia and had a reduced ability to replicate in G26-24 cells.

Molecular cloning and expression of a spike protein of neurovirulent murine coronavirus JHMV variant c1-2

“…Studies in a number of laboratories have shown that there is considerable heterogeneity in the size of the S protein of different MHV isolates (Taguchi et al, 1985, 0001-0654 © 1992.SGM 1986Morris et al, 1989;Parker et al, 1989). We have reported that two variant viruses, cl-2 and CNSV with a larger S protein, are preferentially isolated from rat brains and cultured neural cells (Taguchi et al, 1985(Taguchi et al, , 1986.…”

“…These animals were inoculated with a mixed virus population that consisted predominantly of virus with a smaller S protein and we believe that variants cl-2 and CNSV become the major population in rat brains because of selective growth in rat neural cells (Taguchi et al, 1985;Matsubara et al, 1991). It has also been reported (Morris et al, 1989) that a virus with a smaller S protein, AT1 If cord virus, was isolated from the central nervous system of rats persistently infected with JHMV. AT1 If cord virus has a lower virulence than the virus with a larger S protein originally inoculated into the rat brains.…”

Tumor-secreted SDF-1 promotes glioma invasiveness and TAM tropism toward hypoxia in a murine astrocytoma model

“…Many preclinical glioma models have been reported that are derived by gene targeting in transgenic mice, 4 by carcinogen induction, 5 and by viral infection. 6 Each has drawbacks and restrictions. For example, 4C8 cells from B6D2F1 transgenic mice develop a pattern of necrosis and express glial fibrillary acidic protein (GFAP), but are not very aggressive.…”

No evidence for quasispecies populations during persistence of the coronavirus mouse hepatitis virus JHM: sequence conservation within the surface glycoprotein gene S in Lewis rats.

“…Results from previous studies have indicated that the S gene of coronaviruses plays an important role in virulence and pathogenicity (Taguchi et al, 1985 ;Dalziel et al, 1986 ;Fleming et al, 1986 ;Wege et al, 1988 ;Morris et al, 1989 ;Parker et al, 1989 ;LaMonica et al, 1991 ;Wang et al, 1992). Therefore, we investigated whether coronavirus replication in brain tissue of persistently infected Lewis rats results in an accumulation or selection of S gene variants.…”

“…Several studies have suggested that the S and HE proteins are important determinants for the neuropathogenicity of the virus and for its ability to infect a variety of cell types (Taguchi et al, 1985 ;Morris et al, 1989 ;Parker et al, 1989 ;Wang et al, 1992 ;LaMonica et al, 1991 ;Fazakerley et al, 1992 ;Yokomori et al, 1993). The S protein in particular elicits neutralizing antibodies, binds to cell receptors and causes cell fusion.…”