Spread of mutant middle east respiratory syndrome coronavirus with reduced affinity to human CD26 during the south Korean outbreak

Yuri Kim, Shinhye Cheon, Chan Ki Min, Kyung Mok Sohn, Ying Jin Kang, Young Je Cha, Ju Il Kang, Seong Kyu Han, Na Young Ha, Gwanghun Kim, Abdimadiyeva Aigerim, Hyun Mu Shin, Myung Sik Choi, Sanguk Kim, Hyun Soo Cho, Yeon Sook Kim, Nam Hyuk Cho

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

The newly emerging Middle East respiratory syndrome coronavirus (MERS-CoV) causes a severe respiratory infection with a high mortality rate (~35%). MERS-CoV has been a global threat due to continuous outbreaks in the Arabian peninsula and international spread by infected travelers since 2012. From May to July 2015, a large outbreak initiated by an infected traveler from the Arabian peninsula swept South Korea and resulted in 186 confirmed cases with 38 deaths (case fatality rate, 20.4%). Here, we show the rapid emergence and spread of a mutant MERS-CoV with reduced affinity to the human CD26 receptor during the South Korean outbreak. We isolated 13 new viral genomes from 14 infected patients treated at a hospital and found that 12 of these genomes possess a point mutation in the receptor-binding domain (RBD) of viral spike (S) protein. Specifically, 11 of these genomes have an I529T mutation in RBD, and 1 has a D510G mutation. Strikingly, both mutations result in reduced affinity of RBD to human CD26 compared to wild-type RBD, as measured by surface plasmon resonance analysis and cellular binding assay. Additionally, pseudotyped virus bearing an I529T mutation in S protein showed reduced entry into host cells compared to virus with wild-type S protein. These unexpected findings suggest that MERS-CoV adaptation during human-to-human spread may be driven by host immunological pressure such as neutralizing antibodies, resulting in reduced affinity to host receptor, and thereby impairs viral fitness and virulence, rather than positive selection for a better affinity to CD26.IMPORTANCE Recently, a large outbreak initiated by an MERS-CoV-infected traveler from the Middle East swept South Korea and resulted in 186 confirmed cases with 38 deaths. This is the largest outbreak outside the Middle East, and it raised strong concerns about the possible emergence of MERS-CoV mutations. Here, we isolated 13 new viral genomes and found that 12 of them possess a point mutation in the receptor-binding domain of viral spike protein, resulting in reduced affinity to the human cognate receptor, CD26, compared to the wild-type virus. These unexpected findings suggest that MERS-CoV adaptation in humans may be driven by host immunological pressure.

Original languageEnglish
Article numbere00019-16
JournalmBio
Volume7
Issue number2
DOIs
Publication statusPublished - 2016 Mar 1

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Disease Outbreaks
Protein S
Mutation
Republic of Korea
Middle East
Viral Genome
Viruses
Point Mutation
Genome
Pressure
Surface Plasmon Resonance
Mortality
Viral Proteins
Middle East Respiratory Syndrome Coronavirus
Neutralizing Antibodies
Respiratory Tract Infections
Virulence

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Virology

Cite this

Kim, Y., Cheon, S., Min, C. K., Sohn, K. M., Kang, Y. J., Cha, Y. J., ... Cho, N. H. (2016). Spread of mutant middle east respiratory syndrome coronavirus with reduced affinity to human CD26 during the south Korean outbreak. mBio, 7(2), [e00019-16]. https://doi.org/10.1128/mBio.00019-16
Kim, Yuri ; Cheon, Shinhye ; Min, Chan Ki ; Sohn, Kyung Mok ; Kang, Ying Jin ; Cha, Young Je ; Kang, Ju Il ; Han, Seong Kyu ; Ha, Na Young ; Kim, Gwanghun ; Aigerim, Abdimadiyeva ; Shin, Hyun Mu ; Choi, Myung Sik ; Kim, Sanguk ; Cho, Hyun Soo ; Kim, Yeon Sook ; Cho, Nam Hyuk. / Spread of mutant middle east respiratory syndrome coronavirus with reduced affinity to human CD26 during the south Korean outbreak. In: mBio. 2016 ; Vol. 7, No. 2.
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abstract = "The newly emerging Middle East respiratory syndrome coronavirus (MERS-CoV) causes a severe respiratory infection with a high mortality rate (~35{\%}). MERS-CoV has been a global threat due to continuous outbreaks in the Arabian peninsula and international spread by infected travelers since 2012. From May to July 2015, a large outbreak initiated by an infected traveler from the Arabian peninsula swept South Korea and resulted in 186 confirmed cases with 38 deaths (case fatality rate, 20.4{\%}). Here, we show the rapid emergence and spread of a mutant MERS-CoV with reduced affinity to the human CD26 receptor during the South Korean outbreak. We isolated 13 new viral genomes from 14 infected patients treated at a hospital and found that 12 of these genomes possess a point mutation in the receptor-binding domain (RBD) of viral spike (S) protein. Specifically, 11 of these genomes have an I529T mutation in RBD, and 1 has a D510G mutation. Strikingly, both mutations result in reduced affinity of RBD to human CD26 compared to wild-type RBD, as measured by surface plasmon resonance analysis and cellular binding assay. Additionally, pseudotyped virus bearing an I529T mutation in S protein showed reduced entry into host cells compared to virus with wild-type S protein. These unexpected findings suggest that MERS-CoV adaptation during human-to-human spread may be driven by host immunological pressure such as neutralizing antibodies, resulting in reduced affinity to host receptor, and thereby impairs viral fitness and virulence, rather than positive selection for a better affinity to CD26.IMPORTANCE Recently, a large outbreak initiated by an MERS-CoV-infected traveler from the Middle East swept South Korea and resulted in 186 confirmed cases with 38 deaths. This is the largest outbreak outside the Middle East, and it raised strong concerns about the possible emergence of MERS-CoV mutations. Here, we isolated 13 new viral genomes and found that 12 of them possess a point mutation in the receptor-binding domain of viral spike protein, resulting in reduced affinity to the human cognate receptor, CD26, compared to the wild-type virus. These unexpected findings suggest that MERS-CoV adaptation in humans may be driven by host immunological pressure.",
author = "Yuri Kim and Shinhye Cheon and Min, {Chan Ki} and Sohn, {Kyung Mok} and Kang, {Ying Jin} and Cha, {Young Je} and Kang, {Ju Il} and Han, {Seong Kyu} and Ha, {Na Young} and Gwanghun Kim and Abdimadiyeva Aigerim and Shin, {Hyun Mu} and Choi, {Myung Sik} and Sanguk Kim and Cho, {Hyun Soo} and Kim, {Yeon Sook} and Cho, {Nam Hyuk}",
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Kim, Y, Cheon, S, Min, CK, Sohn, KM, Kang, YJ, Cha, YJ, Kang, JI, Han, SK, Ha, NY, Kim, G, Aigerim, A, Shin, HM, Choi, MS, Kim, S, Cho, HS, Kim, YS & Cho, NH 2016, 'Spread of mutant middle east respiratory syndrome coronavirus with reduced affinity to human CD26 during the south Korean outbreak', mBio, vol. 7, no. 2, e00019-16. https://doi.org/10.1128/mBio.00019-16

Spread of mutant middle east respiratory syndrome coronavirus with reduced affinity to human CD26 during the south Korean outbreak. / Kim, Yuri; Cheon, Shinhye; Min, Chan Ki; Sohn, Kyung Mok; Kang, Ying Jin; Cha, Young Je; Kang, Ju Il; Han, Seong Kyu; Ha, Na Young; Kim, Gwanghun; Aigerim, Abdimadiyeva; Shin, Hyun Mu; Choi, Myung Sik; Kim, Sanguk; Cho, Hyun Soo; Kim, Yeon Sook; Cho, Nam Hyuk.

In: mBio, Vol. 7, No. 2, e00019-16, 01.03.2016.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Spread of mutant middle east respiratory syndrome coronavirus with reduced affinity to human CD26 during the south Korean outbreak

AU - Kim, Yuri

AU - Cheon, Shinhye

AU - Min, Chan Ki

AU - Sohn, Kyung Mok

AU - Kang, Ying Jin

AU - Cha, Young Je

AU - Kang, Ju Il

AU - Han, Seong Kyu

AU - Ha, Na Young

AU - Kim, Gwanghun

AU - Aigerim, Abdimadiyeva

AU - Shin, Hyun Mu

AU - Choi, Myung Sik

AU - Kim, Sanguk

AU - Cho, Hyun Soo

AU - Kim, Yeon Sook

AU - Cho, Nam Hyuk

PY - 2016/3/1

Y1 - 2016/3/1

N2 - The newly emerging Middle East respiratory syndrome coronavirus (MERS-CoV) causes a severe respiratory infection with a high mortality rate (~35%). MERS-CoV has been a global threat due to continuous outbreaks in the Arabian peninsula and international spread by infected travelers since 2012. From May to July 2015, a large outbreak initiated by an infected traveler from the Arabian peninsula swept South Korea and resulted in 186 confirmed cases with 38 deaths (case fatality rate, 20.4%). Here, we show the rapid emergence and spread of a mutant MERS-CoV with reduced affinity to the human CD26 receptor during the South Korean outbreak. We isolated 13 new viral genomes from 14 infected patients treated at a hospital and found that 12 of these genomes possess a point mutation in the receptor-binding domain (RBD) of viral spike (S) protein. Specifically, 11 of these genomes have an I529T mutation in RBD, and 1 has a D510G mutation. Strikingly, both mutations result in reduced affinity of RBD to human CD26 compared to wild-type RBD, as measured by surface plasmon resonance analysis and cellular binding assay. Additionally, pseudotyped virus bearing an I529T mutation in S protein showed reduced entry into host cells compared to virus with wild-type S protein. These unexpected findings suggest that MERS-CoV adaptation during human-to-human spread may be driven by host immunological pressure such as neutralizing antibodies, resulting in reduced affinity to host receptor, and thereby impairs viral fitness and virulence, rather than positive selection for a better affinity to CD26.IMPORTANCE Recently, a large outbreak initiated by an MERS-CoV-infected traveler from the Middle East swept South Korea and resulted in 186 confirmed cases with 38 deaths. This is the largest outbreak outside the Middle East, and it raised strong concerns about the possible emergence of MERS-CoV mutations. Here, we isolated 13 new viral genomes and found that 12 of them possess a point mutation in the receptor-binding domain of viral spike protein, resulting in reduced affinity to the human cognate receptor, CD26, compared to the wild-type virus. These unexpected findings suggest that MERS-CoV adaptation in humans may be driven by host immunological pressure.

AB - The newly emerging Middle East respiratory syndrome coronavirus (MERS-CoV) causes a severe respiratory infection with a high mortality rate (~35%). MERS-CoV has been a global threat due to continuous outbreaks in the Arabian peninsula and international spread by infected travelers since 2012. From May to July 2015, a large outbreak initiated by an infected traveler from the Arabian peninsula swept South Korea and resulted in 186 confirmed cases with 38 deaths (case fatality rate, 20.4%). Here, we show the rapid emergence and spread of a mutant MERS-CoV with reduced affinity to the human CD26 receptor during the South Korean outbreak. We isolated 13 new viral genomes from 14 infected patients treated at a hospital and found that 12 of these genomes possess a point mutation in the receptor-binding domain (RBD) of viral spike (S) protein. Specifically, 11 of these genomes have an I529T mutation in RBD, and 1 has a D510G mutation. Strikingly, both mutations result in reduced affinity of RBD to human CD26 compared to wild-type RBD, as measured by surface plasmon resonance analysis and cellular binding assay. Additionally, pseudotyped virus bearing an I529T mutation in S protein showed reduced entry into host cells compared to virus with wild-type S protein. These unexpected findings suggest that MERS-CoV adaptation during human-to-human spread may be driven by host immunological pressure such as neutralizing antibodies, resulting in reduced affinity to host receptor, and thereby impairs viral fitness and virulence, rather than positive selection for a better affinity to CD26.IMPORTANCE Recently, a large outbreak initiated by an MERS-CoV-infected traveler from the Middle East swept South Korea and resulted in 186 confirmed cases with 38 deaths. This is the largest outbreak outside the Middle East, and it raised strong concerns about the possible emergence of MERS-CoV mutations. Here, we isolated 13 new viral genomes and found that 12 of them possess a point mutation in the receptor-binding domain of viral spike protein, resulting in reduced affinity to the human cognate receptor, CD26, compared to the wild-type virus. These unexpected findings suggest that MERS-CoV adaptation in humans may be driven by host immunological pressure.

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