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

Nat Commun. 2021 Sep 7;12(1):5324. doi: 10.1038/s41467-021-25519-1.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Camelus
  • Cells, Cultured
  • Coronavirus Infections / epidemiology
  • Coronavirus Infections / transmission
  • Coronavirus Infections / virology*
  • Genome, Viral
  • Humans
  • Middle East Respiratory Syndrome Coronavirus / genetics*
  • Middle East Respiratory Syndrome Coronavirus / isolation & purification
  • Middle East Respiratory Syndrome Coronavirus / pathogenicity
  • Phylogeny
  • Recombination, Genetic
  • Republic of Korea / epidemiology
  • Saudi Arabia / epidemiology
  • Virus Replication