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J Infect Dis. Active MERS-CoV replication and aberrant induction of inflammatory cytokines and chemokines in human macrophages: implications for pathogenesis
[Source: The Journal of Infectious Diseases, full page: (LINK). Abstract, edited.]
Active MERS-CoV replication and aberrant induction of inflammatory cytokines and chemokines in human macrophages: implications for pathogenesis
Jie Zhou 1,2,3,*, Hin Chu 2,*, Cun Li 2, Bosco Ho-Yin Wong 2, Zhong-Shan Cheng 2, Vincent Kwok-Man Poon 2, Tianhao Sun 2, Candy Choi-Yi Lau 2, Kenneth Kak-Yuen Wong 5, Jimmy Yu-Wai Chan 5, Jasper Fuk-Woo Chan 1,2,3,4, Kelvin Kai-Wang To 1,2,3,4, Kwok-**** Chan 2, Bo-Jian Zheng 1,2,3,4 and Kwok-Yung Yuen 1,2,3,4,#
Author Affiliations: <SUP>1</SUP>State Key Laboratory of Emerging Infectious Diseases <SUP>2</SUP>Department of Microbiology <SUP>3</SUP>Research Centre of Infection and Immunology <SUP>4</SUP>Carol Yu Centre for Infection <SUP>5</SUP>Department of Surgery; The University of Hong Kong, Hong Kong Special Administrative Region, China
#Correspondence: Kwok-Yung Yuen, 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. Tel: 852-22554897. Fax: 852-28551241. Email: kyyuen@hkucc.hku.hk
* J.Z. and H.C. contributed equally to the study.
Abstract
Middle East respiratory syndrome coronavirus (MERS-CoV) caused severe pneumonia, multi-organ dysfunction and a higher fatality rate (50% versus 10%) than severe acute respiratory syndrome coronavirus (SARS-CoV). To understand the pathogenesis, we studied viral replication, cytokine/chemokine response and antigen presentation in MERS-CoV-infected human monocyte-derived macrophages (MDMs) versus SARS-CoV-infected-MDMs. Only MERS-CoV can replicate in MDMs. Both viruses were unable to significantly stimulate the expression of antiviral cytokines (IFN-α, IFN-β) but induced comparable levels of TNF-α and IL-6. Notably, MERS-CoV induced significantly higher expression levels of IL-12, IFN-γ and chemokines (IP-10/CXCL-10, MCP-1/CCL-2, MIP-1α/CCL-3, RANTES/CCL-5, IL-8) than SARS-CoV. The expression of MHC class I and costimulatory molecules were significantly higher in MERS-CoV-infected-MDMs than in SARS-CoV-infected-cells. MERS-CoV replication was validated by immunostaining of infected MDMs and ex-vivo lung tissue. We conclusively showed that MERS-CoV can establish a productive infection in human macrophages. The aberrant induction of inflammatory cytokines/chemokines could be important in the disease pathogenesis.
Received July 17, 2013. Revision received August 16, 2013. Accepted August 27, 2013. <CITE><ABBR>J Infect Dis.</ABBR> (2013) doi: 10.1093/infdis/jit504 </CITE>First published online: September 24, 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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Active MERS-CoV replication and aberrant induction of inflammatory cytokines and chemokines in human macrophages: implications for pathogenesis
Jie Zhou 1,2,3,*, Hin Chu 2,*, Cun Li 2, Bosco Ho-Yin Wong 2, Zhong-Shan Cheng 2, Vincent Kwok-Man Poon 2, Tianhao Sun 2, Candy Choi-Yi Lau 2, Kenneth Kak-Yuen Wong 5, Jimmy Yu-Wai Chan 5, Jasper Fuk-Woo Chan 1,2,3,4, Kelvin Kai-Wang To 1,2,3,4, Kwok-**** Chan 2, Bo-Jian Zheng 1,2,3,4 and Kwok-Yung Yuen 1,2,3,4,#
Author Affiliations: <SUP>1</SUP>State Key Laboratory of Emerging Infectious Diseases <SUP>2</SUP>Department of Microbiology <SUP>3</SUP>Research Centre of Infection and Immunology <SUP>4</SUP>Carol Yu Centre for Infection <SUP>5</SUP>Department of Surgery; The University of Hong Kong, Hong Kong Special Administrative Region, China
#Correspondence: Kwok-Yung Yuen, 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. Tel: 852-22554897. Fax: 852-28551241. Email: kyyuen@hkucc.hku.hk
* J.Z. and H.C. contributed equally to the study.
Abstract
Middle East respiratory syndrome coronavirus (MERS-CoV) caused severe pneumonia, multi-organ dysfunction and a higher fatality rate (50% versus 10%) than severe acute respiratory syndrome coronavirus (SARS-CoV). To understand the pathogenesis, we studied viral replication, cytokine/chemokine response and antigen presentation in MERS-CoV-infected human monocyte-derived macrophages (MDMs) versus SARS-CoV-infected-MDMs. Only MERS-CoV can replicate in MDMs. Both viruses were unable to significantly stimulate the expression of antiviral cytokines (IFN-α, IFN-β) but induced comparable levels of TNF-α and IL-6. Notably, MERS-CoV induced significantly higher expression levels of IL-12, IFN-γ and chemokines (IP-10/CXCL-10, MCP-1/CCL-2, MIP-1α/CCL-3, RANTES/CCL-5, IL-8) than SARS-CoV. The expression of MHC class I and costimulatory molecules were significantly higher in MERS-CoV-infected-MDMs than in SARS-CoV-infected-cells. MERS-CoV replication was validated by immunostaining of infected MDMs and ex-vivo lung tissue. We conclusively showed that MERS-CoV can establish a productive infection in human macrophages. The aberrant induction of inflammatory cytokines/chemokines could be important in the disease pathogenesis.
Received July 17, 2013. Revision received August 16, 2013. Accepted August 27, 2013. <CITE><ABBR>J Infect Dis.</ABBR> (2013) doi: 10.1093/infdis/jit504 </CITE>First published online: September 24, 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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