10.6084/M9.FIGSHARE.11684145
Hannah Kleine-Weber
Hannah
Kleine-Weber
Simon Schroeder
Simon
Schroeder
Nadine Krüger
Nadine
Krüger
Alexander Prokscha
Alexander
Prokscha
Hassan Y. Naim
Hassan Y.
Naim
Marcel A. Müller
Marcel A.
Müller
Christian Drosten
Christian
Drosten
Stefan Pöhlmann
Stefan
Pöhlmann
Markus Hoffmann
Markus
Hoffmann
Polymorphisms in dipeptidyl peptidase 4 reduce host cell entry of Middle East respiratory syndrome coronavirus
<p>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 (Δ346-348) were compatible with robust DPP4 expression. Four polymorphisms (K267E, K267N, A291P and Δ346-348) 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.</p>
Biophysics
Biochemistry
Microbiology
Genetics
Molecular Biology
Biotechnology
Environmental Sciences not elsewhere classified
Chemical Sciences not elsewhere classified
Immunology
Biological Sciences not elsewhere classified
Cancer
Infectious Diseases
Virology
Taylor & Francis
2023
2023-01-20
2024-02-12
Dataset
7131509 Bytes
10.1080/22221751.2020.1713705
CC BY 4.0