JVI: Adenosine Deaminase Acts as a Natural Antagonist for Dipeptidyl Peptidase 4 Mediated Entry of the Middle East Respiratory Syndrome Coronavirus

[tetano]

Published ahead of print 20 November 2013, doi: 10.1128/JVI.02935-13 JVI.02935-13

Adenosine Deaminase Acts as a Natural Antagonist for Dipeptidyl Peptidase 4 Mediated Entry of the Middle East Respiratory Syndrome Coronavirus

V. Stalin Raja,
Saskia L. Smitsa,b,
Lisette B. Provaciaa,
Judith M.A. van den Branda,
Lidewij Wiersmaa,
Werner J. D. Ouwendijka,
Theo M. Bestebroera,
Monique I. Spronkena,
Geert van Amerongena,
Peter J. M. Rottierc,
Ron A.M. Fouchiera,
Berend Jan Boschc,
Albert D.M.E. Osterhausa,b and
Bart L. Haagmansa

+ Author Affiliations

Department of Viroscience, Erasmus Medical Center, 3000 CA Rotterdam, the Netherlandsa
Viroclinics Biosciences, Marconistraat 16, 3029 AK Rotterdam, the Netherlandsb
Virology Division, Department of Infectious Diseases & Immunology, Faculty of Veterinary Medicine, Utrecht University, 3508 TD Utrecht, the Netherlandsc

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 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.


http://jvi.asm.org/content/early/2013/11/15/JVI.02935-13.abstract