Amino acid substitution L232F in non-structural protein 6 identified as a possible human-adaptive mutation in clade B MERS coronaviruses

J Virol. 2023 Dec 21;97(12):e0136923. doi: 10.1128/jvi.01369-23. Epub 2023 Dec 1.

Abstract

Viral host adaptation plays an important role in inter-species transmission of coronaviruses and influenza viruses. Multiple human-adaptive mutations have been identified in influenza viruses but not so far in MERS-CoV that circulates widely in dromedary camels in the Arabian Peninsula leading to zoonotic transmission. Here, we analyzed clade B MERS-CoV sequences and identified an amino acid substitution L232F in nsp6 that repeatedly occurs in human MERS-CoV. Using a loss-of-function reverse genetics approach, we found the nsp6 L232F conferred increased viral replication competence in vitro, in cultures of the upper human respiratory tract ex vivo, and in lungs of mice infected in vivo. Our results showed that nsp6 L232F may be an adaptive mutation associated with zoonotic transmission of MERS-CoV. This study highlighted the capacity of MERS-CoV to adapt to transmission to humans and also the need for continued surveillance of MERS-CoV in camels.

Keywords: MERS-CoV; coronavirus; nsp6; virus evolution.

MeSH terms

  • Amino Acid Substitution
  • Animals
  • Camelus
  • Coronavirus Infections* / virology
  • Humans
  • Mice
  • Middle East Respiratory Syndrome Coronavirus* / genetics
  • Mutation
  • Viral Nonstructural Proteins* / genetics

Substances

  • Viral Nonstructural Proteins