NDLI: Polymorphisms in dipeptidyl peptidase 4 reduce host cell entry of Middle East respiratory syndrome coronavirus

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Polymorphisms in dipeptidyl peptidase 4 reduce host cell entry of Middle East respiratory syndrome coronavirus

Content Provider	Taylor & Francis Online
Author	Hassan, Y. Naim Krüger, Nadine Schroeder, Simon Pöhlmann, Stefan Müller, Marcel A. Hoffmann, Markus Kleine-weber, Hannah Prokscha, Alexander Drosten, Christian
Abstract	Middle East respiratory syndrome (MERS) coronavirus (MERS-CoV) causes a severe respiratory disease in humans. The MERS-CoV spike (S) glycoprotein mediates viral entry into target cells. For this, MERS-CoV S engages the host cell protein dipeptidyl peptidase 4 (DPP4, CD26) and the interface between MERS-CoV S and DPP4 has been resolved on the atomic level. Here, we asked whether naturally-occurring polymorphisms in DPP4, that alter amino acid residues required for MERS-CoV S binding, influence cellular entry of MERS-CoV. By screening of public databases, we identified fourteen such polymorphisms. Introduction of the respective mutations into DPP4 revealed that all except one (?346-348) were compatible with robust DPP4 expression. Four polymorphisms (K267E, K267N, A291P and ?346-348) strongly reduced binding of MERS-CoV S to DPP4 and S protein-driven host cell entry, as determined using soluble S protein and S protein bearing rhabdoviral vectors, respectively. Two polymorphisms (K267E and A291P) were analyzed in the context of authentic MERS-CoV and were found to attenuate viral replication. Collectively, we identified naturally-occurring polymorphisms in DPP4 that negatively impact cellular entry of MERS-CoV and might thus modulate MERS development in infected patients.
ISSN	22221751
Journal	Emerging Microbes & Infections
DOI	10.1080/22221751.2020.1713705
Language	English
Publisher	Taylor & Francis
Publisher Date	2020-01-21
Access Restriction	Open
Subject Keyword	Middle East respiratory syndrome coronavirus receptor binding polymorphisms spike glycoprotein dipeptidyl peptidase 4
Content Type	Text
Resource Type	Article
Subject	Infectious Diseases Virology Drug Discovery Parasitology Immunology Microbiology Epidemiology

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