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

Author

Listed:
  • 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
    German Centre for Infection Research (DZIF))

  • 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
    Alfaisal University
    Hubert Department of Global Health, Rollins School of Public Health, Emory University)

  • Megan L. Stanifer

    (Heidelberg University Hospital)

  • Steeve Boulant

    (Research Group “Cellular polarity and viral infection”, German Cancer Research Center (DKFZ)
    Virology, Heidelberg University)

  • Mitra Gultom

    (Institute of Virology and Immunology (IVI)
    University of Bern
    University of Bern
    University of Bern)

  • Ronald Dijkman

    (Institute of Virology and Immunology (IVI)
    University of Bern
    University of Bern)

  • 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)
    University of Bern)

  • 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
    German Centre for Infection Research (DZIF)
    Sechenov University)

  • Christian Drosten

    (Institute of Virology, Charité-Universitätsmedizin Berlin
    German Centre for Infection Research (DZIF))

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.

Suggested Citation

  • 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 D, 2021. "Functional comparison of MERS-coronavirus lineages reveals increased replicative fitness of the recombinant lineage 5," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-25519-1
    DOI: 10.1038/s41467-021-25519-1
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