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Differential Cell Line Susceptibility to the Emerging Novel Human Betacoronavirus 2c EMC/2012: Implications for Disease Pathogenesis and Clinical Manifestation

Identifieur interne : 000994 ( Pmc/Checkpoint ); précédent : 000993; suivant : 000995

Differential Cell Line Susceptibility to the Emerging Novel Human Betacoronavirus 2c EMC/2012: Implications for Disease Pathogenesis and Clinical Manifestation

Auteurs : Jasper Fuk-Woo Chan ; Kwok-Hung Chan ; Garnet Kwan-Yue Choi ; Kelvin Kai-Wang To ; Herman Tse ; Jian-Piao Cai ; Man Lung Yeung ; Vincent Chi-Chung Cheng ; Honglin Chen ; Xiao-Yan Che [République populaire de Chine] ; Susanna Kar-Pui Lau ; Patrick Chiu-Yat Woo ; Kwok-Yung Yuen

Source :

RBID : PMC:7107374

Abstract

Abstract

The emerging novel human betacoronavirus 2c EMC/2012 (HCoV-EMC) was recently isolated from patients with severe pneumonia and renal failure and was associated with an unexplained high crude fatality rate of 56%. We performed a cell line susceptibility study with 28 cell lines. HCoV-EMC was found to infect the human respiratory tract (polarized airway epithelium cell line Calu-3, embryonic fibroblast cell line HFL, and lung adenocarcinoma cell line A549), kidney (embryonic kidney cell line HEK), intestinal tract (colorectal adenocarcinoma cell line Caco-2), liver cells (hepatocellular carcinoma cell line Huh-7), and histiocytes (malignant histiocytoma cell line His-1), as evident by detection of high or increasing viral load in culture supernatants, detection of viral nucleoprotein expression by immunostaining, and/or detection of cytopathic effects. Although an infected human neuronal cell line (NT2) and infected monocyte and T lymphocyte cell lines (THP-1, U937, and H9) had increased viral loads, their relatively lower viral production corroborated with absent nucleoprotein expression and cytopathic effects. This range of human tissue tropism is broader than that for all other HCoVs, including SARS coronavirus, HCoV-OC43, HCoV-HKU1, HCoV-229E, and HCoV-NL63, which may explain the high mortality associated with this disease. A recent cell line susceptibility study showed that HCoV-EMC can infect primate, porcine, and bat cells and therefore may jump interspecies barriers. We found that HCoV-EMC can also infect civet lung fibroblast and rabbit kidney cell lines. These findings have important implications for the diagnosis, pathogenesis, and transmission of HCoV-EMC.


Url:
DOI: 10.1093/infdis/jit123
PubMed: 23532101
PubMed Central: 7107374


Affiliations:


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PMC:7107374

Le document en format XML

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<p>The emerging novel human betacoronavirus 2c EMC/2012 (HCoV-EMC) was recently isolated from patients with severe pneumonia and renal failure and was associated with an unexplained high crude fatality rate of 56%. We performed a cell line susceptibility study with 28 cell lines. HCoV-EMC was found to infect the human respiratory tract (polarized airway epithelium cell line Calu-3, embryonic fibroblast cell line HFL, and lung adenocarcinoma cell line A549), kidney (embryonic kidney cell line HEK), intestinal tract (colorectal adenocarcinoma cell line Caco-2), liver cells (hepatocellular carcinoma cell line Huh-7), and histiocytes (malignant histiocytoma cell line His-1), as evident by detection of high or increasing viral load in culture supernatants, detection of viral nucleoprotein expression by immunostaining, and/or detection of cytopathic effects. Although an infected human neuronal cell line (NT2) and infected monocyte and T lymphocyte cell lines (THP-1, U937, and H9) had increased viral loads, their relatively lower viral production corroborated with absent nucleoprotein expression and cytopathic effects. This range of human tissue tropism is broader than that for all other HCoVs, including SARS coronavirus, HCoV-OC43, HCoV-HKU1, HCoV-229E, and HCoV-NL63, which may explain the high mortality associated with this disease. A recent cell line susceptibility study showed that HCoV-EMC can infect primate, porcine, and bat cells and therefore may jump interspecies barriers. We found that HCoV-EMC can also infect civet lung fibroblast and rabbit kidney cell lines. These findings have important implications for the diagnosis, pathogenesis, and transmission of HCoV-EMC.</p>
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<pmc article-type="research-article">
<pmc-dir>properties open_access</pmc-dir>
<front>
<journal-meta>
<journal-id journal-id-type="nlm-ta">J Infect Dis</journal-id>
<journal-id journal-id-type="iso-abbrev">J. Infect. Dis</journal-id>
<journal-id journal-id-type="publisher-id">jid</journal-id>
<journal-id journal-id-type="hwp">jinfdis</journal-id>
<journal-title-group>
<journal-title>The Journal of Infectious Diseases</journal-title>
</journal-title-group>
<issn pub-type="ppub">0022-1899</issn>
<issn pub-type="epub">1537-6613</issn>
<publisher>
<publisher-name>Oxford University Press</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="pmid">23532101</article-id>
<article-id pub-id-type="pmc">7107374</article-id>
<article-id pub-id-type="doi">10.1093/infdis/jit123</article-id>
<article-id pub-id-type="publisher-id">jit123</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Major Articles and Brief Reports</subject>
<subj-group subj-group-type="category-toc-heading">
<subject>Viruses</subject>
</subj-group>
</subj-group>
<subj-group subj-group-type="category-oup-series">
<subject>Editor's Choice</subject>
</subj-group>
</article-categories>
<title-group>
<article-title>Differential Cell Line Susceptibility to the Emerging Novel Human Betacoronavirus 2c EMC/2012: Implications for Disease Pathogenesis and Clinical Manifestation</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname>Chan</surname>
<given-names>Jasper Fuk-Woo</given-names>
</name>
<author-comment>
<title>a</title>
<p>J. F.-W. C. and K.-H. C. contributed equally to the study.</p>
</author-comment>
<xref ref-type="aff" rid="af1">1</xref>
<pmc-comment>kyyuen@hkucc.hku.hk</pmc-comment>
<xref ref-type="corresp" rid="d774016e323"></xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Chan</surname>
<given-names>Kwok-Hung</given-names>
</name>
<author-comment>
<title>a</title>
<p>J. F.-W. C. and K.-H. C. contributed equally to the study.</p>
</author-comment>
<xref ref-type="aff" rid="af1">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Choi</surname>
<given-names>Garnet Kwan-Yue</given-names>
</name>
<xref ref-type="aff" rid="af1">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>To</surname>
<given-names>Kelvin Kai-Wang</given-names>
</name>
<xref ref-type="aff" rid="af1">1</xref>
<xref ref-type="aff" rid="af2">2</xref>
<xref ref-type="aff" rid="af3">3</xref>
<xref ref-type="aff" rid="af4">4</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Tse</surname>
<given-names>Herman</given-names>
</name>
<xref ref-type="aff" rid="af1">1</xref>
<xref ref-type="aff" rid="af2">2</xref>
<xref ref-type="aff" rid="af3">3</xref>
<xref ref-type="aff" rid="af4">4</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Cai</surname>
<given-names>Jian-Piao</given-names>
</name>
<xref ref-type="aff" rid="af1">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Yeung</surname>
<given-names>Man Lung</given-names>
</name>
<xref ref-type="aff" rid="af1">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Cheng</surname>
<given-names>Vincent Chi-Chung</given-names>
</name>
<xref ref-type="aff" rid="af1">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Chen</surname>
<given-names>Honglin</given-names>
</name>
<xref ref-type="aff" rid="af1">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Che</surname>
<given-names>Xiao-Yan</given-names>
</name>
<xref ref-type="aff" rid="af5">5</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Lau</surname>
<given-names>Susanna Kar-Pui</given-names>
</name>
<xref ref-type="aff" rid="af1">1</xref>
<xref ref-type="aff" rid="af2">2</xref>
<xref ref-type="aff" rid="af3">3</xref>
<xref ref-type="aff" rid="af4">4</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Woo</surname>
<given-names>Patrick Chiu-Yat</given-names>
</name>
<xref ref-type="aff" rid="af1">1</xref>
<xref ref-type="aff" rid="af2">2</xref>
<xref ref-type="aff" rid="af3">3</xref>
<xref ref-type="aff" rid="af4">4</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Yuen</surname>
<given-names>Kwok-Yung</given-names>
</name>
<xref ref-type="aff" rid="af1">1</xref>
<xref ref-type="aff" rid="af2">2</xref>
<xref ref-type="aff" rid="af3">3</xref>
<xref ref-type="aff" rid="af4">4</xref>
</contrib>
</contrib-group>
<aff id="af1">
<label>1</label>
<addr-line>Department of Microbiology</addr-line>
</aff>
<aff id="af2">
<label>2</label>
<addr-line>State Key Laboratory of Emerging Infectious Diseases</addr-line>
</aff>
<aff id="af3">
<label>3</label>
<addr-line>Research Centre of Infection and Immunology</addr-line>
</aff>
<aff id="af4">
<label>4</label>
<addr-line>Carol Yu Centre for Infection</addr-line>
,
<institution>the University of Hong Kong, Queen Mary Hospital, Hong Kong Special Administrative Region,</institution>
</aff>
<aff id="af5">
<label>5</label>
<addr-line>Center for Clinical Laboratory</addr-line>
,
<institution>Zhujiang Hospital, Southern Medical University</institution>
,
<addr-line>Guangzhou</addr-line>
,
<country>China</country>
</aff>
<author-notes>
<fn id="AN1">
<label>a</label>
<p>J. F.-W. C. and K.-H. C. contributed equally to the study.</p>
</fn>
<corresp id="d774016e323">Correspondence: Kwok-Yung Yuen, MD, Carol Yu Centre for Infection, Department of Microbiology, The University of Hong Kong, Queen Mary Hospital, 102 Pokfulam Rd, Pokfulam, Hong Kong Special Administrative Region, China (
<email>kyyuen@hkucc.hku.hk</email>
).</corresp>
</author-notes>
<pub-date pub-type="ppub">
<day>1</day>
<month>6</month>
<year>2013</year>
</pub-date>
<pub-date pub-type="epub">
<day>26</day>
<month>3</month>
<year>2013</year>
</pub-date>
<volume>207</volume>
<issue>11</issue>
<fpage>1743</fpage>
<lpage>1752</lpage>
<history>
<date date-type="received">
<day>23</day>
<month>12</month>
<year>2012</year>
</date>
<date date-type="accepted">
<day>10</day>
<month>1</month>
<year>2013</year>
</date>
</history>
<permissions>
<copyright-statement>© The Author 2013. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail:
<email>journals.permissions@oup.com</email>
.</copyright-statement>
<copyright-year>2013</copyright-year>
<license>
<license-p>This article is made available via the PMC Open Access Subset for unrestricted re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the COVID-19 pandemic or until permissions are revoked in writing. Upon expiration of these permissions, PMC is granted a perpetual license to make this article available via PMC and Europe PMC, consistent with existing copyright protections.</license-p>
</license>
</permissions>
<self-uri xlink:href="jit123.pdf"></self-uri>
<related-article related-article-type="article-reference" id="d35e300" vol="207" page="1630" xlink:href="23532103" ext-link-type="pubmed"></related-article>
<abstract>
<title>Abstract</title>
<p>The emerging novel human betacoronavirus 2c EMC/2012 (HCoV-EMC) was recently isolated from patients with severe pneumonia and renal failure and was associated with an unexplained high crude fatality rate of 56%. We performed a cell line susceptibility study with 28 cell lines. HCoV-EMC was found to infect the human respiratory tract (polarized airway epithelium cell line Calu-3, embryonic fibroblast cell line HFL, and lung adenocarcinoma cell line A549), kidney (embryonic kidney cell line HEK), intestinal tract (colorectal adenocarcinoma cell line Caco-2), liver cells (hepatocellular carcinoma cell line Huh-7), and histiocytes (malignant histiocytoma cell line His-1), as evident by detection of high or increasing viral load in culture supernatants, detection of viral nucleoprotein expression by immunostaining, and/or detection of cytopathic effects. Although an infected human neuronal cell line (NT2) and infected monocyte and T lymphocyte cell lines (THP-1, U937, and H9) had increased viral loads, their relatively lower viral production corroborated with absent nucleoprotein expression and cytopathic effects. This range of human tissue tropism is broader than that for all other HCoVs, including SARS coronavirus, HCoV-OC43, HCoV-HKU1, HCoV-229E, and HCoV-NL63, which may explain the high mortality associated with this disease. A recent cell line susceptibility study showed that HCoV-EMC can infect primate, porcine, and bat cells and therefore may jump interspecies barriers. We found that HCoV-EMC can also infect civet lung fibroblast and rabbit kidney cell lines. These findings have important implications for the diagnosis, pathogenesis, and transmission of HCoV-EMC.</p>
</abstract>
<kwd-group>
<kwd>coronavirus</kwd>
<kwd>novel</kwd>
<kwd>HCoV-EMC</kwd>
<kwd>cell line</kwd>
<kwd>susceptibility</kwd>
</kwd-group>
</article-meta>
</front>
</pmc>
<affiliations>
<list>
<country>
<li>République populaire de Chine</li>
</country>
</list>
<tree>
<noCountry>
<name sortKey="Cai, Jian Piao" sort="Cai, Jian Piao" uniqKey="Cai J" first="Jian-Piao" last="Cai">Jian-Piao Cai</name>
<name sortKey="Chan, Jasper Fuk Woo" sort="Chan, Jasper Fuk Woo" uniqKey="Chan J" first="Jasper Fuk-Woo" last="Chan">Jasper Fuk-Woo Chan</name>
<name sortKey="Chan, Kwok Hung" sort="Chan, Kwok Hung" uniqKey="Chan K" first="Kwok-Hung" last="Chan">Kwok-Hung Chan</name>
<name sortKey="Chen, Honglin" sort="Chen, Honglin" uniqKey="Chen H" first="Honglin" last="Chen">Honglin Chen</name>
<name sortKey="Cheng, Vincent Chi Chung" sort="Cheng, Vincent Chi Chung" uniqKey="Cheng V" first="Vincent Chi-Chung" last="Cheng">Vincent Chi-Chung Cheng</name>
<name sortKey="Choi, Garnet Kwan Yue" sort="Choi, Garnet Kwan Yue" uniqKey="Choi G" first="Garnet Kwan-Yue" last="Choi">Garnet Kwan-Yue Choi</name>
<name sortKey="Lau, Susanna Kar Pui" sort="Lau, Susanna Kar Pui" uniqKey="Lau S" first="Susanna Kar-Pui" last="Lau">Susanna Kar-Pui Lau</name>
<name sortKey="To, Kelvin Kai Wang" sort="To, Kelvin Kai Wang" uniqKey="To K" first="Kelvin Kai-Wang" last="To">Kelvin Kai-Wang To</name>
<name sortKey="Tse, Herman" sort="Tse, Herman" uniqKey="Tse H" first="Herman" last="Tse">Herman Tse</name>
<name sortKey="Woo, Patrick Chiu Yat" sort="Woo, Patrick Chiu Yat" uniqKey="Woo P" first="Patrick Chiu-Yat" last="Woo">Patrick Chiu-Yat Woo</name>
<name sortKey="Yeung, Man Lung" sort="Yeung, Man Lung" uniqKey="Yeung M" first="Man Lung" last="Yeung">Man Lung Yeung</name>
<name sortKey="Yuen, Kwok Yung" sort="Yuen, Kwok Yung" uniqKey="Yuen K" first="Kwok-Yung" last="Yuen">Kwok-Yung Yuen</name>
</noCountry>
<country name="République populaire de Chine">
<noRegion>
<name sortKey="Che, Xiao Yan" sort="Che, Xiao Yan" uniqKey="Che X" first="Xiao-Yan" last="Che">Xiao-Yan Che</name>
</noRegion>
</country>
</tree>
</affiliations>
</record>

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