Glycoproteins E2 of the Venezuelan and eastern equine encephalomyelitis viruses contain multiple cross-reactive epitopes.
Enzyme immunoassay (EIA) with sixty types of monoclonal antibodies (MAbs) was used to study cross-reactive epitopes on the attenuated and virulent strains of the Eastern equine encephalomyelitis (EEE) and Venezuelan equine encephalomyelitis (VEE) viruses. All three structural proteins of the EEE and VEE viruses were demonstrated to have both cross-reactive and specific antigenic determinants. The glycoprotein E1 of EEE and VEE viruses possesses three cross-reactive epitopes for binding to MAbs. The glycoprotein E2 has a cluster of epitopes for 20 cross-reacting MAbs produced to EEE and VEE viruses. Cross-reactive epitopes were localised within five different sites of glycoprotein E2 of VEE virus and within four sites of that of the EEE virus. There are no cross-neutralising MAbs to the VEE and EEE viruses. Only one type of the protective Mabs was able to cross-protect mice against lethal infection by the virulent strains of the VEE and EEE viruses. Eight MAbs blocked the hemagglutination activity (HA) of both viruses. Antigenic alterations of neutralising and protective sites were revealed for all attenuated strains of the VEE and EEE viruses. Comparative studies of the E2 proteins amino acid sequences show that the antigenic modifications observed with the attenuated strains of the VEE virus may be caused by multiple amino acid changes in positions 7, 62, 120, 192 and 209-213. The escape-variants of the VEE virus obtained with cross-reactive MAbs 7D1, 2D4 and 7A6 have mutations of the E2 protein at positions 59, 212-213 and 232, respectively. Amino acid sequences in these regions of the VEE and EEE viruses are not homologous. These observations indicate that cross-reactive MAbs are capable of recognising discontinuous epitopes on the E2 glycoprotein.
Pereboev
A V
AV
Institute of Molecular Biology, State Research Centre of Virology and Biotechnology Vector, Koltsovo, Russia.
Razumov
I A
IA
Svyatchenko
V A
VA
Loktev
V B
VB
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal; D005075:Biological Evolution; D002522:Chlorocebus aethiops; D003429:Cross Reactions; D004663:Encephalitis Virus, Eastern Equine / Q000276:immunology* / Q000472:pathogenicity; D004666:Encephalitis Virus, Venezuelan Equine / Q000276:immunology* / Q000472:pathogenicity; D018604:Epitope Mapping; D018985:Epitopes, B-Lymphocyte / Q000276:immunology*; D005260:Female; D006023:Glycoproteins / Q000276:immunology*; D006385:Hemagglutination Inhibition Tests; D007124:Immunoenzyme Techniques; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000276:immunology*; D014774:Virulence
D000911:Antibodies, Monoclonal; D018985:Epitopes, B-Lymphocyte; D006023:Glycoproteins; D014759:Viral Envelope Proteins; C064956:glycoprotein E2, equine encephalitis virus