Virology. Productive replication of Middle East respiratory syndrome coronavirus in monocyte-derived dendritic cells modulates innate immune response

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[Source: ScienceDirect, full page: (LINK). Abstract, edited.]


Virology, Volumes 454?455, April 2014, Pages 197?205 / Brief Communication

Productive replication of Middle East respiratory syndrome coronavirus in monocyte-derived dendritic cells modulates innate immune response

Hin Chu <SUP>a</SUP><SUP>, </SUP><SUP>1</SUP>, Jie Zhou <SUP>a</SUP><SUP>, </SUP><SUP>b</SUP><SUP>, </SUP><SUP>c</SUP><SUP>, </SUP><SUP>1</SUP>, Bosco Ho-Yin Wong <SUP>a</SUP>, Cun Li <SUP>a</SUP>, Zhong-Shan Cheng <SUP>a</SUP>, Xiang Lin <SUP>e</SUP>, Vincent Kwok-Man Poon <SUP>a</SUP>, Tianhao Sun <SUP>a</SUP>, Candy Choi-Yi Lau <SUP>a</SUP>, Jasper Fuk-Woo Chan <SUP>a</SUP><SUP>, </SUP><SUP>b</SUP><SUP>, </SUP><SUP>c</SUP><SUP>, </SUP><SUP>d</SUP>, Kelvin Kai-Wang To <SUP>a</SUP><SUP>, </SUP><SUP>b</SUP><SUP>, </SUP><SUP>c</SUP><SUP>, </SUP><SUP>d</SUP>, Kwok-**** Chan <SUP>a</SUP>, Liwei Lu <SUP>e</SUP>, Bo-Jian Zheng <SUP>a</SUP><SUP>, </SUP><SUP>b</SUP><SUP>, </SUP><SUP>c</SUP><SUP>, </SUP><SUP>d</SUP>, Kwok-Yung Yuen <SUP>a</SUP><SUP>, </SUP><SUP>b</SUP><SUP>, </SUP><SUP>c</SUP><SUP>, </SUP><SUP>d</SUP>
<SUP></SUP>
<SUP>a</SUP> Department of Microbiology, The University of Hong Kong, Hong Kong Special Administrative Region, China - <SUP>b</SUP> State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong Special Administrative Region, China - <SUP>c</SUP> Research Centre of Infection and Immunology, The University of Hong Kong, Hong Kong Special Administrative Region, China - <SUP>d</SUP> Carol Yu Centre for Infection, The University of Hong Kong, Hong Kong Special Administrative Region, China - <SUP>e</SUP> Department of Pathology, The University of Hong Kong, Hong Kong Special Administrative Region, China

Received 6 February 2014, Revised 6 February 2014, Accepted 14 February 2014, Available online 7 March 2014

http://dx.doi.org/10.1016/j.virol.2014.02.018


Highlights

• MERS-CoV productively infected Mo-DCs while SARS-CoV-infection was abortive.
• MERS-CoV induced higher levels of IFN-γ, IP-10, IL-12, and RANTES than SARS-CoV.
• MERS-CoV induced higher surface expression of MHC II and CD86 than SARS-CoV.

Abstract

The Middle East respiratory syndrome coronavirus (MERS-CoV) closely resembled severe acute respiratory syndrome coronavirus (SARS-CoV) in disease manifestation as rapidly progressive acute pneumonia with multi-organ dysfunction. Using monocyte-derived-dendritic cells (Mo-DCs), we discovered fundamental discrepancies in the outcome of MERS‐CoV‐ and SARS-CoV-infection. First, MERS-CoV productively infected Mo-DCs while SARS-CoV-infection was abortive. Second, MERS-CoV induced significantly higher levels of IFN-γ, IP-10, IL-12, and RANTES expression than SARS-CoV. Third, MERS-CoV-infection induced higher surface expression of MHC class II (HLA-DR) and the co-stimulatory molecule CD86 than SARS-CoV-infection. Overall, our data suggests that the dendritic cell can serve as an important target of viral replication and a vehicle for dissemination. MERS-CoV-infection in DCs results in the production of a rich combination of cytokines and chemokines, and modulates innate immune response differently from that of SARS-CoV-infection. Our findings may help to explain the apparent discrepancy in the pathogenicity between MERS-CoV and SARS-CoV.


Keywords

MERS-CoV; SARS-CoV; Viral replication; Pathogenesis; Cytokine and chemokine response; Antigen-presentation

Corresponding author at: 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.: +852 225 548 97; fax: +852 2855 1241.

1 These authors contributed equally to the study.

Copyright ? 2014 Elsevier Inc. All rights reserved.


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