1887

Abstract

Epitopes involved in a protective immune response to (HeV) (, ) were investigated by generating five neutralizing monoclonal antibodies (mAbs) to the virus attachment protein (G) of HeV (HeV G) and sequencing of the G gene of groups of neutralization-escape variants selected with each mAb. Amino acid substitutions occurred at eight distinct sites on HeV G. Relationships between these sites were investigated in binding and neutralization assays using heterologous combinations of variants and mAbs. The sites were also mapped to a proposed structural model for the attachment proteins of . Their specific locations and the nature of their interactions with the mAb panel provided the first functional evidence that HeV G in fact resembled the proposed structure. Four sites (aa 183–185, 417, 447 and 570) contributed to a major discontinuous epitope, on the base of the globular head, that was similar to immunodominant virus neutralization sites found in other paramyxoviruses. Amino acid similarity between HeV and was relatively highly conserved at these sites but decreased significantly at the other sites identified in this study. These included another discontinuous epitope on the base of the head region defined by sites aa 289 and 324 and well separated epitopes on the top of the head at sites aa 191–195 and 385–356. The latter epitope corresponded to immunodominant neutralization sites found in and .

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2005-10-01
2019-10-18
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