Journal
JOURNAL OF GENERAL VIROLOGY
Volume 86, Issue -, Pages 3397-3408Publisher
MICROBIOLOGY SOC
DOI: 10.1099/vir.0.81102-0
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Funding
- NIGMS NIH HHS [GM47157] Funding Source: Medline
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Group A rotaviruses are major intestinal pathogens that express potential alpha 4B1 and alpha 4 beta 7 integrin ligand sequences Leu-Asp-Val and Leu-Asp-IIe in their outer capsid protein VP7, and IIe-Asp-Ala in their spike protein VP4. Monkey rotavirus SA11 can use recombinant alpha 4 beta 1 as a cellular receptor. In this study a new potential alpha 4 beta 1, alpha 4 beta 7 and alpha 9 beta 1 integrin ligand sequence, Tyr-Gly-Leu, was identified in VP4. It was shown that several human and monkey rotaviruses ;bound alpha 4 beta 1 and alpha 4 beta 7, but not alpha 9 beta 1. Binding to alpha 4 beta 1 mediated the infectivity and growth of monkey rotaviruses, and binding to alpha 4 beta 7 mediated their infectivity. A porcine rotavirus interacted with alpha 4 integrins at a post-binding stage to facilitate infection. Activation of alpha 4 beta 1 increased rotavirus infectivity. Cellular treatment with peptides containing the C/A integrin ligand sequences Tyr-Gly-Leu and IIe-Asp-Ala eliminated virus binding to alpha 4 integrins and infectivity. In contrast, rotavirus recognition of alpha 4 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 alpha 4 beta 1 was demonstrated with rotavirus reassortants. Swapping and point mutagenesis of alpha 4 surface loops showed that rotaviruses required the same alpha 4 residues and domains for binding as the natural alpha 4 integrin ligands: mucosal addressin cell adhesion molecule-1, fibronectin and vascular cell adhesion molecule-1. Several rotaviruses are able to use alpha 4 beta 7 and alpha 4 beta 1 for cell binding or entry, through the recognition of the same alpha 4-subunit domains as natural alpha 4 ligands.
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