Rotaviruses interact with α4β7 and α4β1 integrins by binding the same integrin domains as natural ligands

Kate L. Graham, Fiona E. Fleming, Peter Halasz, Marilyn J. Hewish, Hadya S. Nagesha, Ian H. Holmes, Yoshikazu Takada, Barbara S. Coulson

Research output: Contribution to journalArticlepeer-review

49 Citations (Scopus)


Group A rotaviruses are major intestinal pathogens that express potential α4β1 and α4β7 integrin ligand sequences Leu-Asp-Val and Leu-Asp-Ile in their outer capsid protein VP7, and Ile-Asp-Ala in their spike protein VP4. Monkey rotavirus SA11 can use recombinant α4β1 as a cellular receptor. In this study a new potential α4β1, α4β7 and α9β1 integrin ligand sequence, Tyr-Gly-Leu, was identified in VP4. It was shown that several human and monkey rotaviruses bound α4β1 and α4β7, but not α9β1. Binding to α4β1 mediated the infectivity and growth of monkey rotaviruses, and binding to α4β7 mediated their infectivity. A porcine rotavirus interacted with α4 integrins at a post-binding stage to facilitate infection. Activation of α4β1 increased rotavirus infectivity. Cellular treatment with peptides containing the α4 integrin ligand sequences Tyr-Gly-Leu and Ile-Asp-Ala eliminated virus binding to α4 integrins and infectivity. In contrast, rotavirus recognition of α4 integrins was unaffected by a peptide containing the sequence Leu-Asp-Val or by a mutation in the VP7 Leu-Asp-Val sequence. VP4 involvement in rotavirus recognition of α4β1 was demonstrated with rotavirus reassortants. Swapping and point mutagenesis of α4 surface loops showed that rotaviruses required the same α4 residues and domains for binding as the natural α4 integrin ligands: mucosal addressin cell adhesion molecule-1, fibronectin and vascular cell adhesion molecule-1. Several rotaviruses are able to use α4β7 and α4β1 for cell binding or entry, through the recognition of the same α4-subunit domains as natural α4 ligands.

Original languageEnglish
Pages (from-to)3397-3408
Number of pages12
JournalJournal of General Virology
Issue number12
Publication statusPublished - Dec 2005
Externally publishedYes

ASJC Scopus subject areas

  • Virology
  • Immunology


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