Sequence analysis reveals extensive polymorphism and evidence of deletions within the E2 glycoprotein gene of several strains of murine hepatitis virus

Abstract

Direct RNA sequence analysis of the E2 gene of wild-type MHV-4 and of neutralization resistant, neuroattenuated variants has identified a polymorphic region with respect to deletions. These variants had large deletions of 142 to 159 amino acids mapping to a localized region in the amino-terminal domain of the peplomer glycoprotein. The nucleotide sequence of the E2 gene for wild-type strain MHV-4 was found to be very similar to that of MHV-JHM but had an insertion of 423 nucleotides resulting in the addition of a stretch of 141 unique amino acids in the amino-terminal domain of E2. We propose that deletions reflect a major source of heterogeneity in the E2 protein of MHV.

Analysis of a 9.6 kb sequence from the 3' end of canine coronavirus genomic RNA

“…It would appear that there are three regions where deletions can occur at a higher frequency: within S, between S and M, and downstream of N. The polymorphism of S found in MHV strains with differing passage histories is mainly due to deletions in that gene which can lead to deletions of up to 159 amino acids. Consequently, this has an effect on pathogenicity, as deletions in the MHV-4 S coding sequence apparently result in a loss of ability to induce fatal encephalitis and the acquisition of a non-fatal demyelinating disease in mice (Parker et al, 1989). Polymorphism has also been observed in the S gene and in the region between the S and M genes for different strains of TGEV and the respiratory tract mutant, PRCV (Wesley et al, 1990;Rasschaert et al, 1990).…”

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.…”

“…These observations led us to consider the S gene as an indicator molecule for selection processes in vivo. Although the S gene sequence data of tissue culture isolates have revealed a high degree of genetic variability (Parker et al, 1989 ;LaMonica et al, 1991), little is known about the heterogeneity of S gene populations in vivo, especially in association with disease. Therefore, we started to investigate the S gene of virus populations during persistent infection in Lewis rats experimentally infected with MHV.…”

“…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.…”

“…1). The nucleotide sequences of the S gene of MHV-JHM-Pi and the MHV-JHM wild-type gene have a deletion of 453 nucleotides relative to MHV-4 starting at position 1359 and extending through to nucleotide 1781 (Parker et al, 1989). The S gene of MHV-JHM-Pi contains 14 nucleotide substitutions HFA S gene variation in the CNS of Lewis rats S gene variation in the CNS of Lewis rats (point mutations) which all result in amino acid changes (Fig.…”