Characterization of Sindbis virus epitopes important for penetration in cell culture and pathogenesis in animals.
Two anti-glycoprotein E2 monoclonal (MC) antibodies, designated R6 and R13, prepared against an attenuated mutant (SB-RL) of Sindbis virus, preferentially neutralize attenuated, rapidly penetrating strains of Sindbis as opposed to virulent, more slowly penetrating strains. An antigenic variant of SB-RL which displayed reduced reactivity with R6 and R13, demonstrated virulence in suckling mice and slow penetration in baby hamster kidney cells. Anti-E2 MC antibodies to SB-RL and to an independently propagated wild-type Sindbis strain, SIN, were used to compare the topographical relationship of the R6 and R13 epitopes to other E2 antigenic sites. The R6 and R13 epitopes constituted a previously undescribed E2 site, E2-c. Antibody competition experiments using virions in solid phase and in suspension, as well as binding of MC antibody to antigenic variants, demonstrated that E2-c was a spatially distinct and independently mutable site at the surface of Sindbis virions. Of three E2 antigenic sites, E2-a and E2-c were conserved among the Sindbis strains examined, while E2-b was strain specific. Although attenuated strains were preferentially neutralized by E2-c specific MC antibodies, the critical mutation in these strains did not alter their ability to bind E2-c MC antibody. Rather, the mutation was responsible for the altered biological effect of antibody binding at E2-c; the in vitro rapid penetration phenotype; and the in vivo phenotype of attenuation in suckling mice.
R A
RA
Olmsted
W J
WJ
Meyer
R E
RE
Johnston
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000914:Antibodies, Viral / Q000276:immunology*; D000937:Antigen-Antibody Reactions; D000956:Antigens, Viral / Q000276:immunology*; D001667:Binding, Competitive; D000939:Epitopes / Q000276:immunology; D006023:Glycoproteins / Q000276:immunology*; D051379:Mice; D009500:Neutralization Tests; D012845:Sindbis Virus / Q000276:immunology* / Q000472:pathogenicity; D014764:Viral Proteins / Q000276:immunology*; D014774:Virulence
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D000956:Antigens, Viral; D000939:Epitopes; D006023:Glycoproteins; D014764:Viral Proteins