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Adenosine Deaminase Acts as a Natural Antagonist for Dipeptidyl Peptidase 4-Mediated Entry of the Middle East Respiratory Syndrome Coronavirus
Authors:V. Stalin Raj  Saskia L. Smits  Lisette B. Provacia  Judith M. A. van den Brand  Lidewij Wiersma  Werner J. D. Ouwendijk  Theo M. Bestebroer  Monique I. Spronken  Geert van Amerongen  Peter J. M. Rottier  Ron A. M. Fouchier  Berend Jan Bosch  Albert D.M.E. Osterhaus  Bart L. Haagmans
Affiliation:aDepartment of Viroscience, Erasmus Medical Center, Rotterdam, the Netherlands;bViroclinics Biosciences, Rotterdam, the Netherlands;cVirology Division, Department of Infectious Diseases & Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands
Abstract:Middle East respiratory syndrome coronavirus (MERS-CoV) replicates in cells of different species using dipeptidyl peptidase 4 (DPP4) as a functional receptor. Here we show the resistance of ferrets to MERS-CoV infection and inability of ferret DDP4 to bind MERS-CoV. Site-directed mutagenesis of amino acids variable in ferret DPP4 thus revealed the functional human DPP4 virus binding site. Adenosine deaminase (ADA), a DPP4 binding protein, competed for virus binding, acting as a natural antagonist for MERS-CoV infection.
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