Characterization of an antigenic determinant of the glycoprotein that correlates with pathogenicity of rabies virus.

Abstract

The pathogenicity offixed rabies virus strains for adult mice depends on the presence of an antigenic determinant on the viral glycoprotein. Two virus-neutralizing monoclonal antibodies have been used to identify this determinant. All pathogenic strains of fixed rabies virus bind to these antibodies and are neutralized by them, whereas nonpathogenic strains fail to react with these monoclonal antibodies and are not neutralized by them. Antigenic variants of the rabies virus with altered glycoprotein were selected by growing virus in the presence of one monoclonal antibody, 194-2. All variants that lost their ability to react with this antibody and an additional antibody, 248-8, were found to be nonpathogenic for adult mice. Analysis of tryptic peptides of the glycoproteins of pathogenic parent virus and nonpathogenic 'variants and the amino acid sequence of a specific variant tryptic peptide revealed that the change in pathogenicity corresponded to an amino acid substitution at position 333 of the glycoprotein molecule. The nucleotide sequence of the nonpathogenic variant glycoprotein gene contained a base change that confirmed the single amino acid substitution in the tryptic peptide replacing arginine-333 in the parental glycoprotein. We conclude that arginine-333 is essential for the integrity of an antigenic determinant and for the ability of rabies viruses to produce lethal infection in adult mice.

Nucleic acid sequence of the region of the genome encoding capsid protein VP1 of neurovirulent and attenuated type 3 polioviruses

“…It is possible that this single change is responsible for attenuation. For rabies virus, a single amino acid substitution in the surface glycoprotein can have a profound effect on virulence [30]. Perhaps significantly, however, in P3/119 this amino acid does not revert to its original form, showing that the presence of lysine at this position is not obligatory for neurovirulence.…”

Mutations in the glycoprotein of viral haemorrhagic septicaemia virus that affect virulence for fish and the pH threshold for membrane fusion.

“…virulence for adult mice (Coulon et al, 1983 ;Dietzschold et al, 1983 ;Seif et al, 1985 ;Tuffereau et al, 1989). However, attenuated phenotypes were also observed with mutations in the composite antigenic site II : aa 53-61 and 217-222 (Pre!…”

Influenza A virus haemagglutinin polymorphism: pleiotropic antigenic variants of A/Shanghai/11/87 (H3N2) virus selected as high yield reassortants

“…The present results add to previous evidence of influenza virus strain heterogeneity (Kilbourne, 1987;de Jong et al, 1988;Robertson et al, 1991;Katz & Robertson, 1992) and confirm that significantly different antigenic variants identifiable with polyclonal serum as well as MAbs may coexist within a given viral strain. Selection of antigenic variants need not be immunological (Kilbourne, 1980;Erickson & Kilbourne, 1980;Dietzschold et al, 1983). Rather, antigenic change may be the consequence of selection for the hy characteristic (Both et al, 1983), the result of host adaptation (Schild et al, 1983), or may be entirely fortuitous.…”