High-resolution molecular and antigen structure of the VP8* core of a sialic acid-independent human rotavirus strain

Nilah Monnier, Kyoko Higo-Moriguchi, Zhen Yu J. Sun, B. V.Venkataram Prasad, Koki Taniguchi, Philip R. Dormitzer

研究成果: ジャーナルへの寄稿学術論文査読

76 被引用数 (Scopus)

抄録

The most intensively studied rotavirus strains initially attach to cells when the "heads" of their protruding spikes bind cell surface sialic acid. Rotavirus strains that cause disease in humans do not bind this ligand. The structure of the sialic acid binding head (the VP8* core) from the simian rotavirus strain RRV has been reported, and neutralization epitopes have been mapped onto its surface. We report here a 1.6-Å resolution crystal structure of the equivalent domain from the sialic acid-independent rotavirus strain DS-1, which causes gastroenteritis in humans. Although the RRV and DS-1 VP8* cores differ functionally, they share the same galectin-like fold. Differences between the RRV and DS-1 VP8* cores in the region that corresponds to the RRV sialic acid binding site make it unlikely that DS-1 VP8* binds an alternative carbohydrate ligand in this location. In the crystals, a surface cleft on each DS-1 VP8* core binds N-terminal residues from a neighboring molecule. This cleft may function as a ligand binding site during rotavirus replication. We also report an escape mutant analysis, which allows the mapping of heterotypic neutralizing epitopes recognized by human monoclonal antibodies onto the surface of the VP8* core. The distribution of escape mutations on the DS-1 VP8* core indicates that neutralizing antibodies that recognize VP8* of human rotavirus strains may bind a conformation of the spike that differs from those observed to date.

本文言語英語
ページ(範囲)1513-1523
ページ数11
ジャーナルJournal of Virology
80
3
DOI
出版ステータス出版済み - 02-2006

All Science Journal Classification (ASJC) codes

  • 微生物学
  • 免疫学
  • 昆虫科学
  • ウイルス学

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