Overexpression of the nucleocapsid protein of Middle East respiratory syndrome coronavirus up-regulates CXCL10.

James Odame Aboagye,Oi-Wing Ng,Ali Mirazimi,Yee-Joo Tan,Vanessa M Monteil,Chow Wenn Yew

doi:10.1042/bsr20181059

Abstract

Middle East respiratory syndrome coronavirus (MERS-CoV) causes respiratory diseases in humans and has a high mortality rate. During infection, MERS-CoV regulates several host cellular processes including antiviral response genes. In order to determine if the nucleocapsid protein of MERS-CoV (MERS-N) plays a role in viral–host interactions, a murine monoclonal antibody was generated so as to allow detection of the protein in infected cells as well as in overexpression system. Then, MERS-N was stably overexpressed in A549 cells, and a PCR array containing 84 genes was used to screen for genes transcriptionally regulated by it. Several up-regulated antiviral genes, namely TNF, IL6, IL8, and CXCL10, were selected for independent validation in transiently transfected 293FT cells. Out of these, the overexpression of MERS-N was found to up-regulate CXCL10 at both transcriptional and translational levels. Interestingly, CXCL10 has been reported to be up-regulated in MERS-CoV infected airway epithelial cells and lung fibroblast cells, as well as monocyte-derived macrophages and dendritic cells. High secretions and persistent increase of CXCL10 in MERS-CoV patients have been also associated with severity of disease. To our knowledge, this is the first report showing that the MERS-N protein is one of the contributing factors for CXCL10 up-regulation during infection. In addition, our results showed that a fragment consisting of residues 196–413 in MERS-N is sufficient to up-regulate CXCL10, while the N-terminal domain and serine-arginine (SR)-rich motif of MERS-N do not play a role in this up-regulation.

Highlights

Middle East respiratory syndrome coronavirus (MERS-CoV) is a nidovirus and etiologic agent for respiratory disease
Our results suggest that the MERS-N protein is one of the contributing factors for C-X-C motif chemokine 10 (CXCL10) up-regulation during infection
This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons

Summary

Introduction

Middle East respiratory syndrome coronavirus (MERS-CoV) is a nidovirus and etiologic agent for respiratory disease. Manifestations of MERS disease are similar to severe acute respiratory syndrome (SARS) with patients usually developing acute pneumonia that progresses to respiratory failure and acute respiratory disease syndrome [2]. Patients exhibit extrapulmonary manifestations include renal failure, hepatic dysfunction, and diarrhoea with some severe cases of deranged coagulation profile and hematological changes [3-5]. MERS-CoV is an enveloped, single-stranded, positive-sense RNA virus, approximately 30 kb in length with two-thirds of its genome encoding 15–16 non-structural proteins (nsp) [6,7]. N primarily encapsidates the viral genome and plays important roles in viral replication, virus particle c 2018 The Author(s).

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