Giuseppe
Emeritus
[Source: Journal of Infectious Diseases, full text: (LINK). Abstract, edited.]
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Differential cell line susceptibility to the emerging novel human betacoronavirus 2c EMC/2012: implications on disease pathogenesis and clinical manifestation
Jasper Fuk-Woo Chan 1,*, Kwok-Hung Chan 1,*, Garnet Kwan-Yue Choi 1, Kelvin Kai-Wang To 1,2,3,4, Herman Tse 1,2,3,4, Jian-Piao Cai 1, Man Lung Yeung 1, Vincent Chi-Chung Cheng 1, Honglin Chen 1, Xiao-Yan Che 5, Susanna Kar-Pui Lau 1,2,3,4, Patrick Chiu-Yat Woo 1,2,3,4 and Kwok-Yung Yuen 1,2,3,4,#
Author Affiliations: <SUP>1</SUP>Department of Microbiology <SUP>2</SUP>State Key Laboratory of Emerging Infectious Diseases <SUP>3</SUP>Research Centre of Infection and Immunology <SUP>4</SUP>Carol Yu Centre for Infection, the University of Hong Kong, Queen Mary Hospital, Hong Kong Special Administrative Region, China <SUP>5</SUP>Center for Clinical Laboratory, Zhujiang Hospital, Southern Medical University, Guangzhou, China
#Corresponding author. Mailing address: Carol Yu Centre for Infection, Department of Microbiology, The University of Hong Kong, Queen Mary Hospital, 102 Pokfulam Road, Pokfulam, Hong Kong Special Administrative Region, China. Phone: (852) 22554892. Fax: (852) 28551241. E-mail: kyyuen@hkucc.hku.hk
* The authors contributed equally to the manuscript
Abstract
The emerging novel human betacoronavirus 2c EMC/2012 (HCoV-EMC) was recently isolated from patients with severe pneumonia and renal failure associated with an unexplained high crude fatality rate of 56%. We performed a cell line susceptibility study with 27 cell lines. HCoV-EMC can infect human respiratory (polarized airway epithelium, Calu-3; embryonic fibroblasts, HFL; lung adenocarcinoma, A549), kidney (embryonic kidney, HEK), intestinal (colorectal adenocarcinoma, Caco-2), liver (hepatocellular carcinoma, Huh-7) cells and histiocytes (malignant histiocytoma, His-1) as evident by a high or increasing viral load in culture supernatants, immunostaining for viral nucleoprotein expression and/or cytopathic effect (CPE). Though infected human neuronal cells (NT2) and monocytes (THP-1, U937) had increase in viral load, their relatively lower viral production corroborated with absent nucleoprotein expression and CPE. This range of human tissue tropism is broader than all other human coronaviruses including SARS-CoV, HCoV-OC43, HCoV-HKU1, HCoV-229E and HCoV-NL63 which may explain the high mortality of 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 on the diagnosis, pathogenesis and transmission of HCoV-EMC.
Footnotes
Received December 23, 2012. Revision received January 8, 2013. Accepted January 10, 2013.
? 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: journals.permissions@oup.com
-Jasper Fuk-Woo Chan 1,*, Kwok-Hung Chan 1,*, Garnet Kwan-Yue Choi 1, Kelvin Kai-Wang To 1,2,3,4, Herman Tse 1,2,3,4, Jian-Piao Cai 1, Man Lung Yeung 1, Vincent Chi-Chung Cheng 1, Honglin Chen 1, Xiao-Yan Che 5, Susanna Kar-Pui Lau 1,2,3,4, Patrick Chiu-Yat Woo 1,2,3,4 and Kwok-Yung Yuen 1,2,3,4,#
Author Affiliations: <SUP>1</SUP>Department of Microbiology <SUP>2</SUP>State Key Laboratory of Emerging Infectious Diseases <SUP>3</SUP>Research Centre of Infection and Immunology <SUP>4</SUP>Carol Yu Centre for Infection, the University of Hong Kong, Queen Mary Hospital, Hong Kong Special Administrative Region, China <SUP>5</SUP>Center for Clinical Laboratory, Zhujiang Hospital, Southern Medical University, Guangzhou, China
#Corresponding author. Mailing address: Carol Yu Centre for Infection, Department of Microbiology, The University of Hong Kong, Queen Mary Hospital, 102 Pokfulam Road, Pokfulam, Hong Kong Special Administrative Region, China. Phone: (852) 22554892. Fax: (852) 28551241. E-mail: kyyuen@hkucc.hku.hk
* The authors contributed equally to the manuscript
Abstract
The emerging novel human betacoronavirus 2c EMC/2012 (HCoV-EMC) was recently isolated from patients with severe pneumonia and renal failure associated with an unexplained high crude fatality rate of 56%. We performed a cell line susceptibility study with 27 cell lines. HCoV-EMC can infect human respiratory (polarized airway epithelium, Calu-3; embryonic fibroblasts, HFL; lung adenocarcinoma, A549), kidney (embryonic kidney, HEK), intestinal (colorectal adenocarcinoma, Caco-2), liver (hepatocellular carcinoma, Huh-7) cells and histiocytes (malignant histiocytoma, His-1) as evident by a high or increasing viral load in culture supernatants, immunostaining for viral nucleoprotein expression and/or cytopathic effect (CPE). Though infected human neuronal cells (NT2) and monocytes (THP-1, U937) had increase in viral load, their relatively lower viral production corroborated with absent nucleoprotein expression and CPE. This range of human tissue tropism is broader than all other human coronaviruses including SARS-CoV, HCoV-OC43, HCoV-HKU1, HCoV-229E and HCoV-NL63 which may explain the high mortality of 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 on the diagnosis, pathogenesis and transmission of HCoV-EMC.
Footnotes
Received December 23, 2012. Revision received January 8, 2013. Accepted January 10, 2013.
? 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: journals.permissions@oup.com
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