Nat Commun
. 2021 Sep 7;12(1):5324.
doi: 10.1038/s41467-021-25519-1.
Functional comparison of MERS-coronavirus lineages reveals increased replicative fitness of the recombinant lineage 5
Simon Schroeder 1 , Christin Mache 2 , Hannah Kleine-Weber 3 , Victor M Corman 1 4 , Doreen Muth 1 , Anja Richter 1 , Diana Fatykhova 5 , Ziad A Memish 6 7 8 , Megan L Stanifer 9 , Steeve Boulant 10 11 , Mitra Gultom 12 13 14 15 , Ronald Dijkman 12 13 14 , Stephan Eggeling 16 , Andreas Hocke 5 , Stefan Hippenstiel 5 , Volker Thiel 12 13 , Stefan Pöhlmann 3 , Thorsten Wolff 2 , Marcel A Müller 1 4 17 , Christian Drosten 18 19
Affiliations
- PMID: 34493730
- DOI: 10.1038/s41467-021-25519-1
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.