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

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

Research output: Contribution to journalArticle

61 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1513-1523
Number of pages11
JournalJournal of Virology
Volume80
Issue number3
DOIs
Publication statusPublished - 01-02-2006

Fingerprint

sialic acids
Rotavirus
N-Acetylneuraminic Acid
Molecular Structure
antigens
Antigens
Ligands
neutralization
epitopes
Epitopes
binding sites
Binding Sites
Head
Galectins
gastroenteritis
Gastroenteritis
crystal structure
Neutralizing Antibodies
neutralizing antibodies
human diseases

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

Monnier, Nilah ; Moriguchi, Kyoko ; Sun, Zhen Yu J. ; Prasad, B. V.Venkataram ; Taniguchi, Koki ; Dormitzer, Philip R. / High-resolution molecular and antigen structure of the VP8* core of a sialic acid-independent human rotavirus strain. In: Journal of Virology. 2006 ; Vol. 80, No. 3. pp. 1513-1523.
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High-resolution molecular and antigen structure of the VP8* core of a sialic acid-independent human rotavirus strain. / Monnier, Nilah; Moriguchi, Kyoko; Sun, Zhen Yu J.; Prasad, B. V.Venkataram; Taniguchi, Koki; Dormitzer, Philip R.

In: Journal of Virology, Vol. 80, No. 3, 01.02.2006, p. 1513-1523.

Research output: Contribution to journalArticle

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AU - Monnier, Nilah

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