Gewählte Publikation:
Kriegshäuser, G; Wutz, G; Lea, S; Stuart, D; Skern, T; Kuechler, E.
Model of the equine rhinitis A virus capsid: identification of a major neutralizing immunogenic site.
J Gen Virol. 2003; 84(Pt 9):2365-2373
Doi: 10.1099/vir.0.19232-0
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- Führende Autor*innen der Med Uni Graz
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Kriegshäuser Gernot
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- Abstract:
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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).
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Amino Acid Sequence -
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Animals -
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Aphthovirus - genetics Aphthovirus - immunology
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Binding Sites, Antibody -
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Capsid - chemistry Capsid - immunology
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Epitopes - chemistry
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Genome, Viral -
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Mice -
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Mice, Inbred BALB C -
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Models, Molecular -
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Molecular Sequence Data -
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Mutation -
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Neutralization Tests -
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Sequence Alignment -