The MERS-CoV isolated during the 2015 nosocomial outbreak in Korea showed distinctive differences in mortality and transmission patterns compared to the prototype MERS-CoV EMC strain belonging to clade A. We established a BAC-based reverse genetics system for a Korean isolate of MERS-CoV KNIH002 in the clade B phylogenetically far from the EMC strain, and generated a recombinant MERS-CoV expressing red fluorescent protein. The virus rescued from the infectious clone and KNIH002 strain displayed growth attenuation compared to the EMC strain. Consecutive passages of the rescued virus rapidly generated various ORF5 variants, highlighting its genetic instability and calling for caution in the use of repeatedly passaged virus in pathogenesis studies and for evaluation of control measures against MERS-CoV. The infectious clone for the KNIH002 in contemporary epidemic clade B would be useful for better understanding of a functional link between molecular evolution and pathophysiology of MERS-CoV by comparative studies with EMC strain.
Bibliographical noteFunding Information:
This work was supported by a grant [KCDC 2016HD16A1229] from the Korea Centers for Disease Control and Prevention and in part by the National Research Foundation of Korea (NRF) grants [NRF 2019R1H1A2078176 and 2020M3E9A1041759] funded by the Ministry of Science and ICT, South Korea (MSIT) and by the Brain Korea 21 (BK21) four program. H.C. was supported by a postdoctoral fellowship from the BK21 four program. M.K. was partially supported by the Graduate School of Yonsei University Research Scholarship Grants in 2019. We thank Bart Haagmans (Department of Viroscience, Erasmus Medical Center, Rotterdam, the Netherlands) and Luis Enjuanes (Campus Universidad Aut?noma, Cantoblanco, Madrid, Spain) for reagents.
All Science Journal Classification (ASJC) codes
- Drug Discovery
- Infectious Diseases