Rotavirus spike protein VP5* binds α2β1 integrin on the cell surface and competes with virus for cell binding and infectivity

Kate L. Graham, Yoshikazu Takada, Barbara S. Coulson

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Rotaviruses recognize several cell-surface molecules, including the α2β1 integrin, and the processes of rotavirus cell attachment and entry appear to be multifactorial. The VP5* subunit of the rotavirus spike protein VP4 contains the α2β1 ligand sequence Asp-Gly-Glu at residues 308-310. Binding to α2β1 and infectivity of monkey rotavirus strain RRV and human rotavirus strain Wa, but not porcine rotavirus strain CRW-8, are inhibited by peptides containing Asp-Gly-Glu. Asp308 and Gly309 are necessary for the binding of RRV VP5* (aa 248-474) to expressed I domain of the α2 integrin subunit. Here, the ability of RRV VP5* to bind cells and affect rotavirus-integrin interactions was determined. Interestingly, VP5* bound to cells at 4 and 37 °C, both via α2β1 and independently of this integrin. Prior VP5* binding at 37 °C eliminated RRV binding to cellular α2β1 and reduced RRV and Wa infectivity in MA104 cells by 38-46%. VP5* binding did not affect the infectivity of CRW-8. VP5* binding at 4 °C did not affect permissive-cell infection by RRV, indicating an energy requirement for VP5* competition with virus for infectivity. Mutagenesis of VP5* Asp308 and Gly309 eliminated VP5* binding to a2#1 and the VP5*inhibition of rotavirus cell binding and infection, but not α2β1-independent cell binding by VP5*. These studies show for the first time that expressed VP5* binds cell-surface α2β1 using Asp308 and Gly309 and inhibits the infection of homologous and heterologous rotaviruses that use α2β1 as a receptor. cr 2006 SGM.

Original languageEnglish
Pages (from-to)1275-1283
Number of pages9
JournalJournal of General Virology
Volume87
Issue number5
DOIs
Publication statusPublished - May 2006
Externally publishedYes

ASJC Scopus subject areas

  • Virology
  • Immunology

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