An infectious cDNA clone of a growth attenuated Korean isolate of MERS coronavirus KNIH002 in clade B

Minwoo Kim; Hee Cho; Seung Hoon Lee; Woo Jung Park; Jeong Min Kim; Jae Su Moon; Geon Woo Kim; Wooseong Lee; Hae Gwang Jung; Jeong Sun Yang; Jang Hoon Choi; Joo Yeon Lee; Sung Soon Kim; Jong Won Oh

doi:10.1080/22221751.2020.1861914

An infectious cDNA clone of a growth attenuated Korean isolate of MERS coronavirus KNIH002 in clade B

Minwoo Kim, Hee Cho, Seung Hoon Lee, Woo Jung Park, Jeong Min Kim, Jae Su Moon, Geon Woo Kim, Wooseong Lee, Hae Gwang Jung, Jeong Sun Yang, Jang Hoon Choi, Joo Yeon Lee, Sung Soon Kim, Jong Won Oh

Research output: Contribution to journal › Article › peer-review

3 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	2714-2726
Number of pages	13
Journal	Emerging Microbes and Infections
Volume	9
Issue number	1
DOIs	https://doi.org/10.1080/22221751.2020.1861914
Publication status	Published - 2020

Bibliographical note

Funding 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 Autónoma, Cantoblanco, Madrid, Spain) for reagents.

Publisher Copyright:
© 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group, on behalf of Shanghai Shangyixun Cultural Communication Co., Ltd.

All Science Journal Classification (ASJC) codes

Drug Discovery
Infectious Diseases
Epidemiology
Virology
Parasitology
Microbiology
Immunology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1080/22221751.2020.1861914

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Kim, M., Cho, H., Lee, S. H., Park, W. J., Kim, J. M., Moon, J. S., Kim, G. W., Lee, W., Jung, H. G., Yang, J. S., Choi, J. H., Lee, J. Y., Kim, S. S., & Oh, J. W. (2020). An infectious cDNA clone of a growth attenuated Korean isolate of MERS coronavirus KNIH002 in clade B. Emerging Microbes and Infections, 9(1), 2714-2726. https://doi.org/10.1080/22221751.2020.1861914

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title = "An infectious cDNA clone of a growth attenuated Korean isolate of MERS coronavirus KNIH002 in clade B",

abstract = "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.",

author = "Minwoo Kim and Hee Cho and Lee, {Seung Hoon} and Park, {Woo Jung} and Kim, {Jeong Min} and Moon, {Jae Su} and Kim, {Geon Woo} and Wooseong Lee and Jung, {Hae Gwang} and Yang, {Jeong Sun} and Choi, {Jang Hoon} and Lee, {Joo Yeon} and Kim, {Sung Soon} and Oh, {Jong Won}",

note = "Funding 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{\'o}noma, Cantoblanco, Madrid, Spain) for reagents. Publisher Copyright: {\textcopyright} 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group, on behalf of Shanghai Shangyixun Cultural Communication Co., Ltd.",

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AU - Kim, Minwoo

AU - Cho, Hee

AU - Lee, Seung Hoon

AU - Park, Woo Jung

AU - Kim, Jeong Min

AU - Moon, Jae Su

AU - Kim, Geon Woo

AU - Lee, Wooseong

AU - Jung, Hae Gwang

AU - Yang, Jeong Sun

AU - Choi, Jang Hoon

AU - Lee, Joo Yeon

AU - Kim, Sung Soon

AU - Oh, Jong Won

N1 - Funding 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 Autónoma, Cantoblanco, Madrid, Spain) for reagents. Publisher Copyright: © 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group, on behalf of Shanghai Shangyixun Cultural Communication Co., Ltd.

PY - 2020

Y1 - 2020

N2 - 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.

AB - 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.

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ER -

An infectious cDNA clone of a growth attenuated Korean isolate of MERS coronavirus KNIH002 in clade B

Abstract

Bibliographical note

All Science Journal Classification (ASJC) codes

UN SDGs

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