Variants of Venezuelan equine encephalitis virus that resist neutralization define a domain of the E2 glycoprotein.
Stable neutralization (N) escape variants of Venezuelan equine encephalitis (VEE) virus were selected by anti-E2 glycoprotein monoclonal antibodies (MAbs) that neutralize viral infectivity, block viral hemagglutination, and passively protect mice. The nucleotide sequence of the E1, E2, and E3 genes of four variants revealed a clustering of single mutations in a domain spanning E2-182 to E2-207. The conformation of this short linear sequence affects antigenicity in the N domain because reduction and alkylation of virus disrupted binding of some E2 neutralizing MAbs. Serologic evidence for interaction of E2 epitopes also was obtained. Mutations in the N domain of VEE virus did not alter the kinetics of binding to Vero cells. They did, in some cases, produce attenuation of virulence in mice.
Johnson
B J
BJ
Division of Vector-Borne Viral Diseases, Centers for Disease Control, Fort Collins, Colorado 80522.
Brubaker
J R
JR
Roehrig
J T
JT
Trent
D W
DW
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000956:Antigens, Viral / Q000235:genetics*; D001483:Base Sequence; D004666:Encephalitis Virus, Venezuelan Equine / Q000235:genetics* / Q000276:immunology / Q000472:pathogenicity; D000939:Epitopes / Q000032:analysis; D014644:Genetic Variation; D008969:Molecular Sequence Data; D009154:Mutation; D009500:Neutralization Tests; D012367:RNA, Viral / Q000235:genetics; D012689:Sequence Homology, Nucleic Acid; D012984:Software; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000235:genetics* / Q000276:immunology; D014774:Virulence
D000911:Antibodies, Monoclonal; D000956:Antigens, Viral; D000939:Epitopes; D012367:RNA, Viral; D014759:Viral Envelope Proteins; C064956:glycoprotein E2, equine encephalitis virus