Isolation and characterization of a bat SARS-like coronavirus that uses the ACE2 receptor

Whole-genome sequences of two novel SARS-CoV-related bat coronaviruses, in addition to a live isolate of a bat SARS-like coronavirus, are reported; the live isolate can infect human cells using ACE2, providing the strongest evidence to date that Chinese horseshoe bats are natural reservoirs of SARS-...

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Published inNature (London) Vol. 503; no. 7477; pp. 535 - 538
Main Authors Ge, Xing-Yi, Li, Jia-Lu, Yang, Xing-Lou, Chmura, Aleksei A., Zhu, Guangjian, Epstein, Jonathan H., Mazet, Jonna K., Hu, Ben, Zhang, Wei, Peng, Cheng, Zhang, Yu-Ji, Luo, Chu-Ming, Tan, Bing, Wang, Ning, Zhu, Yan, Crameri, Gary, Zhang, Shu-Yi, Wang, Lin-Fa, Daszak, Peter, Shi, Zheng-Li
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group UK 29.11.2013
Nature Publishing Group
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Abstract Whole-genome sequences of two novel SARS-CoV-related bat coronaviruses, in addition to a live isolate of a bat SARS-like coronavirus, are reported; the live isolate can infect human cells using ACE2, providing the strongest evidence to date that Chinese horseshoe bats are natural reservoirs of SARS-CoV. A SARS-like virus in bats Peter Daszak and colleagues identify two novel coronaviruses from Chinese horseshoe bats that are closely related to severe acute respiratory syndrome coronavirus (SARS-CoV), the cause of a pandemic during 2002 and 2003. They also isolate a live virus from these bats that has high sequence identity to SARS-CoV and that can infect human cells using ACE2, the same receptor that is used by SARS-CoV. The results provide the strongest evidence to date that horseshoe bats are natural reservoirs of SARS-CoV. The 2002–3 pandemic caused by severe acute respiratory syndrome coronavirus (SARS-CoV) was one of the most significant public health events in recent history 1 . An ongoing outbreak of Middle East respiratory syndrome coronavirus 2 suggests that this group of viruses remains a key threat and that their distribution is wider than previously recognized. Although bats have been suggested to be the natural reservoirs of both viruses 3 , 4 , 5 , attempts to isolate the progenitor virus of SARS-CoV from bats have been unsuccessful. Diverse SARS-like coronaviruses (SL-CoVs) have now been reported from bats in China, Europe and Africa 5 , 6 , 7 , 8 , but none is considered a direct progenitor of SARS-CoV because of their phylogenetic disparity from this virus and the inability of their spike proteins to use the SARS-CoV cellular receptor molecule, the human angiotensin converting enzyme II (ACE2) 9 , 10 . Here we report whole-genome sequences of two novel bat coronaviruses from Chinese horseshoe bats (family: Rhinolophidae) in Yunnan, China: RsSHC014 and Rs3367. These viruses are far more closely related to SARS-CoV than any previously identified bat coronaviruses, particularly in the receptor binding domain of the spike protein. Most importantly, we report the first recorded isolation of a live SL-CoV (bat SL-CoV-WIV1) from bat faecal samples in Vero E6 cells, which has typical coronavirus morphology, 99.9% sequence identity to Rs3367 and uses ACE2 from humans, civets and Chinese horseshoe bats for cell entry. Preliminary in vitro testing indicates that WIV1 also has a broad species tropism. Our results provide the strongest evidence to date that Chinese horseshoe bats are natural reservoirs of SARS-CoV, and that intermediate hosts may not be necessary for direct human infection by some bat SL-CoVs. They also highlight the importance of pathogen-discovery programs targeting high-risk wildlife groups in emerging disease hotspots as a strategy for pandemic preparedness.
AbstractList Whole-genome sequences of two novel SARS-CoV-related bat coronaviruses, in addition to a live isolate of a bat SARS-like coronavirus, are reported; the live isolate can infect human cells using ACE2, providing the strongest evidence to date that Chinese horseshoe bats are natural reservoirs of SARS-CoV.
Whole-genome sequences of two novel SARS-CoV-related bat coronaviruses, in addition to a live isolate of a bat SARS-like coronavirus, are reported; the live isolate can infect human cells using ACE2, providing the strongest evidence to date that Chinese horseshoe bats are natural reservoirs of SARS-CoV. A SARS-like virus in bats Peter Daszak and colleagues identify two novel coronaviruses from Chinese horseshoe bats that are closely related to severe acute respiratory syndrome coronavirus (SARS-CoV), the cause of a pandemic during 2002 and 2003. They also isolate a live virus from these bats that has high sequence identity to SARS-CoV and that can infect human cells using ACE2, the same receptor that is used by SARS-CoV. The results provide the strongest evidence to date that horseshoe bats are natural reservoirs of SARS-CoV. The 2002-3 pandemic caused by severe acute respiratory syndrome coronavirus (SARS-CoV) was one of the most significant public health events in recent history.sup.1. An ongoing outbreak of Middle East respiratory syndrome coronavirus.sup.2 suggests that this group of viruses remains a key threat and that their distribution is wider than previously recognized. Although bats have been suggested to be the natural reservoirs of both viruses.sup.3,4,5, attempts to isolate the progenitor virus of SARS-CoV from bats have been unsuccessful. Diverse SARS-like coronaviruses (SL-CoVs) have now been reported from bats in China, Europe and Africa.sup.5,6,7,8, but none is considered a direct progenitor of SARS-CoV because of their phylogenetic disparity from this virus and the inability of their spike proteins to use the SARS-CoV cellular receptor molecule, the human angiotensin converting enzyme II (ACE2).sup.9,10. Here we report whole-genome sequences of two novel bat coronaviruses from Chinese horseshoe bats (family: Rhinolophidae) in Yunnan, China: RsSHC014 and Rs3367. These viruses are far more closely related to SARS-CoV than any previously identified bat coronaviruses, particularly in the receptor binding domain of the spike protein. Most importantly, we report the first recorded isolation of a live SL-CoV (bat SL-CoV-WIV1) from bat faecal samples in Vero E6 cells, which has typical coronavirus morphology, 99.9% sequence identity to Rs3367 and uses ACE2 from humans, civets and Chinese horseshoe bats for cell entry. Preliminary in vitro testing indicates that WIV1 also has a broad species tropism. Our results provide the strongest evidence to date that Chinese horseshoe bats are natural reservoirs of SARS-CoV, and that intermediate hosts may not be necessary for direct human infection by some bat SL-CoVs. They also highlight the importance of pathogen-discovery programs targeting high-risk wildlife groups in emerging disease hotspots as a strategy for pandemic preparedness.
The 2002-3 pandemic caused by severe acute respiratory syndrome coronavirus (SARS-CoV) was one of the most significant public health events in recent history (1). An ongoing outbreak of Middle East respiratory syndrome coronavirus (2) suggests that this group of viruses remains a key threat and that their distribution is wider than previously recognized. Although bats have been suggested to be the natural reservoirs of both viruses (3-5), attempts to isolate the progenitor virus of SARS-CoV from bats have been unsuccessful. Diverse SARS-like coronaviruses (SL-CoVs) have now been reported from bats in China, Europe and Africa (5-8), but none is considered a direct progenitor of SARS-CoV because of their phylogenetic disparity from this virus and the inability of their spike proteins to use the SARS-CoV cellular receptor molecule, the human angiotensin converting enzyme II (ACE2) (9,10). Here we report whole-genome sequences of two novel bat coronaviruses from Chinese horseshoe bats (family: Rhinolophidae) in Yunnan, China: RsSHC014 and Rs3367. These viruses are far more closely related to SARS-CoV than any previously identified bat coronaviruses, particularly in the receptor binding domain of the spike protein. Most importantly, we report the first recorded isolation of a live SL-CoV (bat SL-CoV-WIVl) from bat faecal samples in Vero E6 cells, which has typical coronavirus morphology, 99.9% sequence identity to Rs3367 and uses ACE2 from humans, civets and Chinese horseshoe bats for cell entry. Preliminary in vitro testing indicates that WIV1 also has a broad species tropism. Our results provide the strongest evidence to date that Chinese horseshoe bats are natural reservoirs of SARS-CoV, and that intermediate hosts may not be necessary for direct human infection by some bat SL-CoVs. They also highlight the importance of pathogen-discovery programs targeting high-risk wildlife groups in emerging disease hotspots as a strategy for pandemic preparedness.
The 2002-3 pandemic caused by severe acute respiratory syndrome coronavirus (SARS-CoV) was one of the most significant public health events in recent history. An ongoing outbreak of Middle East respiratory syndrome coronavirus suggests that this group of viruses remains a key threat and that their distribution is wider than previously recognized. Although bats have been suggested to be the natural reservoirs of both viruses, attempts to isolate the progenitor virus of SARS-CoV from bats have been unsuccessful. Diverse SARS-like coronaviruses (SL-CoVs) have now been reported from bats in China, Europe and Africa, but none is considered a direct progenitor of SARS-CoV because of their phylogenetic disparity from this virus and the inability of their spike proteins to use the SARS-CoV cellular receptor molecule, the human angiotensin converting enzyme II (ACE2). Here we report whole-genome sequences of two novel bat coronaviruses from Chinese horseshoe bats (family: Rhinolophidae) in Yunnan, China: RsSHC014 and Rs3367. These viruses are far more closely related to SARS-CoV than any previously identified bat coronaviruses, particularly in the receptor binding domain of the spike protein. Most importantly, we report the first recorded isolation of a live SL-CoV (bat SL-CoV-WIV1) from bat faecal samples in Vero E6 cells, which has typical coronavirus morphology, 99.9% sequence identity to Rs3367 and uses ACE2 from humans, civets and Chinese horseshoe bats for cell entry. Preliminary in vitro testing indicates that WIV1 also has a broad species tropism. Our results provide the strongest evidence to date that Chinese horseshoe bats are natural reservoirs of SARS-CoV, and that intermediate hosts may not be necessary for direct human infection by some bat SL-CoVs. They also highlight the importance of pathogen-discovery programs targeting high-risk wildlife groups in emerging disease hotspots as a strategy for pandemic preparedness.
The 2002-3 pandemic caused by severe acute respiratory syndrome coronavirus (SARS-CoV) was one of the most significant public health events in recent history. An ongoing outbreak of Middle East respiratory syndrome coronavirus suggests that this group of viruses remains a key threat and that their distribution is wider than previously recognized. Although bats have been suggested to be the natural reservoirs of both viruses, attempts to isolate the progenitor virus of SARS-CoV from bats have been unsuccessful. Diverse SARS-like coronaviruses (SL-CoVs) have now been reported from bats in China, Europe and Africa, but none is considered a direct progenitor of SARS-CoV because of their phylogenetic disparity from this virus and the inability of their spike proteins to use the SARS-CoV cellular receptor molecule, the human angiotensin converting enzyme II (ACE2). Here we report whole-genome sequences of two novel bat coronaviruses from Chinese horseshoe bats (family: Rhinolophidae) in Yunnan, China: RsSHC014 and Rs3367. These viruses are far more closely related to SARS-CoV than any previously identified bat coronaviruses, particularly in the receptor binding domain of the spike protein. Most importantly, we report the first recorded isolation of a live SL-CoV (bat SL-CoV-WIVl) from bat faecal samples in Vero E6 cells, which has typical coronavirus morphology, 99.9% sequence identity to Rs3367 and uses ACE2 from humans, civets and Chinese horseshoe bats for cell entry. Preliminary in vitro testing indicates that WIV1 also has a broad species tropism. Our results provide the strongest evidence to date that Chinese horseshoe bats are natural reservoirs of SARS-CoV, and that intermediate hosts may not be necessary for direct human infection by some bat SL-CoV s. They also highlight the importance of pathogen-discovery programs targeting high-risk wildlife groups in emerging disease hotspots as a strategy for pandemic preparedness. [PUBLICATION ABSTRACT]
Whole-genome sequences of two novel SARS-CoV-related bat coronaviruses, in addition to a live isolate of a bat SARS-like coronavirus, are reported; the live isolate can infect human cells using ACE2, providing the strongest evidence to date that Chinese horseshoe bats are natural reservoirs of SARS-CoV. A SARS-like virus in bats Peter Daszak and colleagues identify two novel coronaviruses from Chinese horseshoe bats that are closely related to severe acute respiratory syndrome coronavirus (SARS-CoV), the cause of a pandemic during 2002 and 2003. They also isolate a live virus from these bats that has high sequence identity to SARS-CoV and that can infect human cells using ACE2, the same receptor that is used by SARS-CoV. The results provide the strongest evidence to date that horseshoe bats are natural reservoirs of SARS-CoV. The 2002–3 pandemic caused by severe acute respiratory syndrome coronavirus (SARS-CoV) was one of the most significant public health events in recent history 1 . An ongoing outbreak of Middle East respiratory syndrome coronavirus 2 suggests that this group of viruses remains a key threat and that their distribution is wider than previously recognized. Although bats have been suggested to be the natural reservoirs of both viruses 3 , 4 , 5 , attempts to isolate the progenitor virus of SARS-CoV from bats have been unsuccessful. Diverse SARS-like coronaviruses (SL-CoVs) have now been reported from bats in China, Europe and Africa 5 , 6 , 7 , 8 , but none is considered a direct progenitor of SARS-CoV because of their phylogenetic disparity from this virus and the inability of their spike proteins to use the SARS-CoV cellular receptor molecule, the human angiotensin converting enzyme II (ACE2) 9 , 10 . Here we report whole-genome sequences of two novel bat coronaviruses from Chinese horseshoe bats (family: Rhinolophidae) in Yunnan, China: RsSHC014 and Rs3367. These viruses are far more closely related to SARS-CoV than any previously identified bat coronaviruses, particularly in the receptor binding domain of the spike protein. Most importantly, we report the first recorded isolation of a live SL-CoV (bat SL-CoV-WIV1) from bat faecal samples in Vero E6 cells, which has typical coronavirus morphology, 99.9% sequence identity to Rs3367 and uses ACE2 from humans, civets and Chinese horseshoe bats for cell entry. Preliminary in vitro testing indicates that WIV1 also has a broad species tropism. Our results provide the strongest evidence to date that Chinese horseshoe bats are natural reservoirs of SARS-CoV, and that intermediate hosts may not be necessary for direct human infection by some bat SL-CoVs. They also highlight the importance of pathogen-discovery programs targeting high-risk wildlife groups in emerging disease hotspots as a strategy for pandemic preparedness.
Whole-genome sequences of two novel SARS-CoV-related bat coronaviruses, in addition to a live isolate of a bat SARS-like coronavirus, are reported; the live isolate can infect human cells using ACE2, providing the strongest evidence to date that Chinese horseshoe bats are natural reservoirs of SARS-CoV. Peter Daszak and colleagues identify two novel coronaviruses from Chinese horseshoe bats that are closely related to severe acute respiratory syndrome coronavirus (SARS-CoV), the cause of a pandemic during 2002 and 2003. They also isolate a live virus from these bats that has high sequence identity to SARS-CoV and that can infect human cells using ACE2, the same receptor that is used by SARS-CoV. The results provide the strongest evidence to date that horseshoe bats are natural reservoirs of SARS-CoV. The 2002–3 pandemic caused by severe acute respiratory syndrome coronavirus (SARS-CoV) was one of the most significant public health events in recent history 1 . An ongoing outbreak of Middle East respiratory syndrome coronavirus 2 suggests that this group of viruses remains a key threat and that their distribution is wider than previously recognized. Although bats have been suggested to be the natural reservoirs of both viruses 3 , 4 , 5 , attempts to isolate the progenitor virus of SARS-CoV from bats have been unsuccessful. Diverse SARS-like coronaviruses (SL-CoVs) have now been reported from bats in China, Europe and Africa 5 , 6 , 7 , 8 , but none is considered a direct progenitor of SARS-CoV because of their phylogenetic disparity from this virus and the inability of their spike proteins to use the SARS-CoV cellular receptor molecule, the human angiotensin converting enzyme II (ACE2) 9 , 10 . Here we report whole-genome sequences of two novel bat coronaviruses from Chinese horseshoe bats (family: Rhinolophidae) in Yunnan, China: RsSHC014 and Rs3367. These viruses are far more closely related to SARS-CoV than any previously identified bat coronaviruses, particularly in the receptor binding domain of the spike protein. Most importantly, we report the first recorded isolation of a live SL-CoV (bat SL-CoV-WIV1) from bat faecal samples in Vero E6 cells, which has typical coronavirus morphology, 99.9% sequence identity to Rs3367 and uses ACE2 from humans, civets and Chinese horseshoe bats for cell entry. Preliminary in vitro testing indicates that WIV1 also has a broad species tropism. Our results provide the strongest evidence to date that Chinese horseshoe bats are natural reservoirs of SARS-CoV, and that intermediate hosts may not be necessary for direct human infection by some bat SL-CoVs. They also highlight the importance of pathogen-discovery programs targeting high-risk wildlife groups in emerging disease hotspots as a strategy for pandemic preparedness.
Audience Academic
Author Daszak, Peter
Luo, Chu-Ming
Epstein, Jonathan H.
Zhang, Wei
Mazet, Jonna K.
Wang, Ning
Zhu, Guangjian
Hu, Ben
Zhang, Yu-Ji
Shi, Zheng-Li
Wang, Lin-Fa
Li, Jia-Lu
Yang, Xing-Lou
Peng, Cheng
Crameri, Gary
Chmura, Aleksei A.
Zhang, Shu-Yi
Tan, Bing
Ge, Xing-Yi
Zhu, Yan
Author_xml – sequence: 1
  givenname: Xing-Yi
  surname: Ge
  fullname: Ge, Xing-Yi
  organization: Center for Emerging Infectious Diseases, State Key Laboratory of Virology, Wuhan Institute of Virology of the Chinese Academy of Sciences
– sequence: 2
  givenname: Jia-Lu
  surname: Li
  fullname: Li, Jia-Lu
  organization: Center for Emerging Infectious Diseases, State Key Laboratory of Virology, Wuhan Institute of Virology of the Chinese Academy of Sciences
– sequence: 3
  givenname: Xing-Lou
  surname: Yang
  fullname: Yang, Xing-Lou
  organization: Center for Emerging Infectious Diseases, State Key Laboratory of Virology, Wuhan Institute of Virology of the Chinese Academy of Sciences
– sequence: 4
  givenname: Aleksei A.
  surname: Chmura
  fullname: Chmura, Aleksei A.
  organization: EcoHealth Alliance
– sequence: 5
  givenname: Guangjian
  surname: Zhu
  fullname: Zhu, Guangjian
  organization: EcoHealth Alliance
– sequence: 6
  givenname: Jonathan H.
  surname: Epstein
  fullname: Epstein, Jonathan H.
  organization: EcoHealth Alliance
– sequence: 7
  givenname: Jonna K.
  surname: Mazet
  fullname: Mazet, Jonna K.
  organization: One Health Institute, School of Veterinary Medicine, University of California
– sequence: 8
  givenname: Ben
  surname: Hu
  fullname: Hu, Ben
  organization: Center for Emerging Infectious Diseases, State Key Laboratory of Virology, Wuhan Institute of Virology of the Chinese Academy of Sciences
– sequence: 9
  givenname: Wei
  surname: Zhang
  fullname: Zhang, Wei
  organization: Center for Emerging Infectious Diseases, State Key Laboratory of Virology, Wuhan Institute of Virology of the Chinese Academy of Sciences
– sequence: 10
  givenname: Cheng
  surname: Peng
  fullname: Peng, Cheng
  organization: Center for Emerging Infectious Diseases, State Key Laboratory of Virology, Wuhan Institute of Virology of the Chinese Academy of Sciences
– sequence: 11
  givenname: Yu-Ji
  surname: Zhang
  fullname: Zhang, Yu-Ji
  organization: Center for Emerging Infectious Diseases, State Key Laboratory of Virology, Wuhan Institute of Virology of the Chinese Academy of Sciences
– sequence: 12
  givenname: Chu-Ming
  surname: Luo
  fullname: Luo, Chu-Ming
  organization: Center for Emerging Infectious Diseases, State Key Laboratory of Virology, Wuhan Institute of Virology of the Chinese Academy of Sciences
– sequence: 13
  givenname: Bing
  surname: Tan
  fullname: Tan, Bing
  organization: Center for Emerging Infectious Diseases, State Key Laboratory of Virology, Wuhan Institute of Virology of the Chinese Academy of Sciences
– sequence: 14
  givenname: Ning
  surname: Wang
  fullname: Wang, Ning
  organization: Center for Emerging Infectious Diseases, State Key Laboratory of Virology, Wuhan Institute of Virology of the Chinese Academy of Sciences
– sequence: 15
  givenname: Yan
  surname: Zhu
  fullname: Zhu, Yan
  organization: Center for Emerging Infectious Diseases, State Key Laboratory of Virology, Wuhan Institute of Virology of the Chinese Academy of Sciences
– sequence: 16
  givenname: Gary
  surname: Crameri
  fullname: Crameri, Gary
  organization: CSIRO Australian Animal Health Laboratory
– sequence: 17
  givenname: Shu-Yi
  surname: Zhang
  fullname: Zhang, Shu-Yi
  organization: College of Life Sciences, East China Normal University, Shanghai 200062, China
– sequence: 18
  givenname: Lin-Fa
  surname: Wang
  fullname: Wang, Lin-Fa
  organization: CSIRO Australian Animal Health Laboratory, Emerging Infectious Diseases Program, Duke-NUS Graduate Medical School, Singapore 169857
– sequence: 19
  givenname: Peter
  surname: Daszak
  fullname: Daszak, Peter
  email: daszak@ecohealthalliance.org
  organization: EcoHealth Alliance
– sequence: 20
  givenname: Zheng-Li
  surname: Shi
  fullname: Shi, Zheng-Li
  email: zlshi@wh.iov.cn
  organization: Center for Emerging Infectious Diseases, State Key Laboratory of Virology, Wuhan Institute of Virology of the Chinese Academy of Sciences
BackLink https://www.ncbi.nlm.nih.gov/pubmed/24172901$$D View this record in MEDLINE/PubMed
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    fullname: NL Ithete
– volume: 82
  start-page: 1899
  year: 2008
  ident: BFnature12711_CR9
  publication-title: J. Virol.
  doi: 10.1128/JVI.01085-07
  contributor:
    fullname: W Ren
SSID ssj0005174
Score 2.6813815
Snippet Whole-genome sequences of two novel SARS-CoV-related bat coronaviruses, in addition to a live isolate of a bat SARS-like coronavirus, are reported; the live...
The 2002-3 pandemic caused by severe acute respiratory syndrome coronavirus (SARS-CoV) was one of the most significant public health events in recent history....
The 2002-3 pandemic caused by severe acute respiratory syndrome coronavirus (SARS-CoV) was one of the most significant public health events in recent history...
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StartPage 535
SubjectTerms 631/326/596/2078
Angiotensin-Converting Enzyme 2
Animals
Bats
China
Chiroptera - virology
Chlorocebus aethiops
Coronaviruses
COVID-19
Disease Reservoirs - virology
Distribution
Epidemics
Feces - virology
Fluorescent Antibody Technique
Genes
Genetic aspects
Genetic diversity
Genome, Viral - genetics
Genomes
Health aspects
Host Specificity
Humanities and Social Sciences
Humans
Identification and classification
letter
Microbiology
Molecular Sequence Data
multidisciplinary
Pandemics
Pandemics - prevention & control
Pandemics - veterinary
Peptidyl-Dipeptidase A - genetics
Peptidyl-Dipeptidase A - metabolism
Phylogenetics
Proteins
Public health
Real-Time Polymerase Chain Reaction
Receptors, Virus - genetics
Receptors, Virus - metabolism
RNA polymerase
SARS Virus - genetics
SARS Virus - isolation & purification
SARS Virus - metabolism
SARS Virus - ultrastructure
Science
Severe acute respiratory syndrome
Severe Acute Respiratory Syndrome - prevention & control
Severe Acute Respiratory Syndrome - transmission
Severe Acute Respiratory Syndrome - veterinary
Severe Acute Respiratory Syndrome - virology
Species Specificity
Spike Glycoprotein, Coronavirus - chemistry
Spike Glycoprotein, Coronavirus - metabolism
Vero Cells
Viral genetics
Virion - isolation & purification
Virion - ultrastructure
Virus Internalization
Viverridae - metabolism
Wildlife
Zoonoses
Title Isolation and characterization of a bat SARS-like coronavirus that uses the ACE2 receptor
URI https://link.springer.com/article/10.1038/nature12711
https://www.ncbi.nlm.nih.gov/pubmed/24172901
https://www.proquest.com/docview/1467746338
https://search.proquest.com/docview/1462763706
https://pubmed.ncbi.nlm.nih.gov/PMC5389864
Volume 503
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