Effects on rotavirus cell binding and infection of monomeric and polymeric peptides containing α2β1 and αxβ2 integrin ligand sequences

Kate L. Graham, Weiguang Zeng, Yoshikazu Takada, David C. Jackson, Barbara S. Coulson

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26 引文 斯高帕斯(Scopus)

摘要

Integrin-using rotaviruses bind MA104 cell surface α2β1 integrin via the Asp-Gly-Glu (DGE) sequence in virus spike protein VP4 and interact with αxβ2 integrin during cell entry through outer capsid protein VP7. Infection is inhibited by the α2β1 ligand Asp-Gly-Glu-Ala (DGEA) and the αxβ2 ligand Gly-Pro-Arg-Pro (GPRP), and virus-α2β1 binding is increased by α2β1 activation. In this study, we analyzed the effects of monomers and polymers containing DGEA-, GPRP-, and DGEA-related peptides on rotavirus binding and infection in intestinal (Caco-2) and kidney (MA104) cells and virus binding to recombinant α2β1. Blockade of rotavirus-cell binding and infection by peptides and anti-α2 antibody showed that Caco-2 cell entry is dependent on virus binding to α2β1 and interaction with αxβ2. At up to 0.5 mM, monomeric DGEA and DGAA inbibited binding to α2β1 and infection. At higher concentrations, DGEA and DGAA showed a reduced ability to inhibit virus-cell binding and infection that depended on virus binding to α2β1 but occurred without alteration in cell surface expression of α2, β2, or αvβ3 integrin. This loss of DGEA activity was abolished by genistein treatment and so was dependent on tyrosine kinase signaling. It is proposed that this signaling activated existing cell surface α2β1 to increase virus-cell attachment and entry. Polymeric peptides containing DGEA and GPRP or GPRP only were inhibitory to SA11 infection at approximately 10-fold lower concentrations than peptide monomers. As polymerization can improve peptide inhibition of virus-receptor interactions, this approach could be useful in the development of inhibitors of receptor recognition by other viruses.

原文英語
頁(從 - 到)11786-11797
頁數12
期刊Journal of Virology
78
發行號21
DOIs
出版狀態已發佈 - 十一月 2004
對外發佈Yes

ASJC Scopus subject areas

  • Immunology

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