Functional comparison of MERS-coronavirus lineages reveals increased replicative fitness of the recombinant lineage 5

Simon Schroeder, Christin Mache, Hannah Kleine-Weber, Victor M. Corman, Doreen Muth, Anja Richter, Diana Fatykhova, Ziad A. Memish, Megan L. Stanifer, Steeve Boulant, Mitra Gultom, Ronald Dijkman, Stephan Eggeling, Andreas Hocke, Stefan Hippenstiel, Volker Thiel, Stefan Pöhlmann, Thorsten Wolff, Marcel A. Müller and Christian Drosten ()
Additional contact information
Simon Schroeder: Institute of Virology, Charité-Universitätsmedizin Berlin
Christin Mache: Unit 17, Influenza and other Respiratory Viruses, Robert Koch Institut
Hannah Kleine-Weber: Infection Biology Unit, German Primate Center – Leibniz Institute for Primate Research
Victor M. Corman: Institute of Virology, Charité-Universitätsmedizin Berlin
Doreen Muth: Institute of Virology, Charité-Universitätsmedizin Berlin
Anja Richter: Institute of Virology, Charité-Universitätsmedizin Berlin
Diana Fatykhova: Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health
Ziad A. Memish: Research and Innovation Department, King Saud Medical City, Ministry of Health
Megan L. Stanifer: Heidelberg University Hospital
Steeve Boulant: Research Group “Cellular polarity and viral infection”, German Cancer Research Center (DKFZ)
Mitra Gultom: Institute of Virology and Immunology (IVI)
Ronald Dijkman: Institute of Virology and Immunology (IVI)
Stephan Eggeling: Vivantes Clinics Neukölln
Andreas Hocke: Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health
Stefan Hippenstiel: Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health
Volker Thiel: Institute of Virology and Immunology (IVI)
Stefan Pöhlmann: Infection Biology Unit, German Primate Center – Leibniz Institute for Primate Research
Thorsten Wolff: Unit 17, Influenza and other Respiratory Viruses, Robert Koch Institut
Marcel A. Müller: Institute of Virology, Charité-Universitätsmedizin Berlin
Christian Drosten: Institute of Virology, Charité-Universitätsmedizin Berlin

Nature Communications, 2021, vol. 12, issue 1, 1-13

Abstract: Abstract Middle East respiratory syndrome coronavirus (MERS-CoV) is enzootic in dromedary camels across the Middle East and Africa. Virus-induced pneumonia in humans results from animal contact, with a potential for limited onward transmission. Phenotypic changes have been suspected after a novel recombinant clade (lineage 5) caused large nosocomial outbreaks in Saudi Arabia and South Korea in 2016. However, there has been no functional assessment. Here we perform a comprehensive in vitro and ex vivo comparison of viruses from parental and recombinant virus lineages (lineage 3, n = 7; lineage 4, n = 8; lineage 5, n = 9 viruses) from Saudi Arabia, isolated immediately before and after the shift toward lineage 5. Replication of lineage 5 viruses is significantly increased. Transcriptional profiling finds reduced induction of immune genes IFNB1, CCL5, and IFNL1 in lung cells infected with lineage 5 strains. Phenotypic differences may be determined by IFN antagonism based on experiments using IFN receptor knock out and signaling inhibition. Additionally, lineage 5 is more resilient against IFN pre-treatment of Calu-3 cells (ca. 10-fold difference in replication). This phenotypic change associated with lineage 5 has remained undiscovered by viral sequence surveillance, but may be a relevant indicator of pandemic potential.

Date: 2021
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DOI: 10.1038/s41467-021-25519-1

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