Rotavirus spike protein VP5* binds alpha2beta1 integrin on the cell surface and competes with virus for cell binding and infectivity

J Gen Virol. 2006 May;87(Pt 5):1275-1283. doi: 10.1099/vir.0.81580-0.


Rotaviruses recognize several cell-surface molecules, including the alpha2beta1 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 alpha2beta1 ligand sequence Asp-Gly-Glu at residues 308-310. Binding to alpha2beta1 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 alpha2 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 degrees C, both via alpha2beta1 and independently of this integrin. Prior VP5* binding at 37 degrees C eliminated RRV binding to cellular alpha2beta1 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 degrees 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 alpha2beta1 and the VP5* inhibition of rotavirus cell binding and infection, but not alpha2beta1-independent cell binding by VP5*. These studies show for the first time that expressed VP5* binds cell-surface alpha2beta1 using Asp308 and Gly309 and inhibits the infection of homologous and heterologous rotaviruses that use alpha2beta1 as a receptor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aspartic Acid
  • Capsid Proteins / chemistry
  • Cell Line
  • Glutamic Acid
  • Glycine
  • Humans
  • Integrin alpha2beta1 / chemistry
  • Integrin alpha2beta1 / metabolism*
  • Receptors, Virus / metabolism
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / metabolism
  • Rotavirus / physiology*
  • Rotavirus Infections / prevention & control*
  • Rotavirus Infections / virology
  • Species Specificity
  • Viral Nonstructural Proteins / genetics
  • Viral Nonstructural Proteins / metabolism*
  • Virus Replication


  • Capsid Proteins
  • Integrin alpha2beta1
  • Receptors, Virus
  • Recombinant Proteins
  • VP4 protein, Rotavirus
  • Viral Nonstructural Proteins
  • nsp1 protein, Rotavirus
  • Aspartic Acid
  • Glutamic Acid
  • Glycine