Model of the equine rhinitis A virus capsid: identification of a major neutralizing immunogenic site.
Mouse monoclonal antibodies (mAbs) were employed to select neutralization escape mutants of equine rhinitis A virus (ERAV). Amino acid changes in the ERAV mutants resulting in resistance to neutralization were identified in capsid protein VP1 at Lys-114, Pro-240 and Thr-241. Although the changes were located in different parts of the polypeptide chain, these mutants exhibited cross-resistance against all four mAbs employed, indicating that these residues contribute to a single immunogenic site. To explain this result, we constructed a model of the three-dimensional structure of the ERAV capsid based on comparison with the closely related foot-and-mouth disease virus (FMDV O(1)). According to this model, VP1 is folded so that Lys-114 is in the beta E-beta F loop of the polypeptide chain at a considerable distance from Pro-240 and Trp-241 in the C-terminal region. However, around the fivefold axis of symmetry, the C terminus of VP1 in each protomer extends to the beta E-beta F loop of the adjacent VP1 in the next protomer. We therefore propose that the immunogenic site in ERAV is formed as a result of the close proximity of the Lys-114 residue in the beta E-beta F loop of one VP1 molecule and of the Pro-240/Thr-241 residues in the adjacent VP1 polypeptide chain. In terms of the overall architecture of the viral capsid structure, this site in ERAV most closely resembles the immunogenic site 1 of FMDV O(1).
Kriegshäuser
Gernot
G
Max F. Perutz Laboratories, University Departments at the Vienna Biocenter, Department of Medical Biochemistry, Division of Biochemistry, University of Vienna, Dr Bohr Gasse 9/3, A-1030 Vienna, Austria.
Wutz
Gordana
G
Max F. Perutz Laboratories, University Departments at the Vienna Biocenter, Department of Medical Biochemistry, Division of Biochemistry, University of Vienna, Dr Bohr Gasse 9/3, A-1030 Vienna, Austria.
Lea
Susan
S
Laboratory of Molecular Biophysics, Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.
Stuart
David
D
Laboratory of Molecular Biophysics, Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.
Skern
Tim
T
Max F. Perutz Laboratories, University Departments at the Vienna Biocenter, Department of Medical Biochemistry, Division of Biochemistry, University of Vienna, Dr Bohr Gasse 9/3, A-1030 Vienna, Austria.
Kuechler
Ernst
E
Max F. Perutz Laboratories, University Departments at the Vienna Biocenter, Department of Medical Biochemistry, Division of Biochemistry, University of Vienna, Dr Bohr Gasse 9/3, A-1030 Vienna, Austria.
D000595:Amino Acid Sequence; D000818:Animals; D005537:Aphthovirus / Q000235:genetics / Q000276:immunology*; D001666:Binding Sites, Antibody; D002213:Capsid / Q000737:chemistry / Q000276:immunology*; D000939:Epitopes / Q000737:chemistry; D016679:Genome, Viral; D051379:Mice; D008807:Mice, Inbred BALB C; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D009500:Neutralization Tests; D016415:Sequence Alignment
D000939:Epitopes