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

• Published in: Bioscience reports Vol. 38; no. 5
• Main Authors: Aboagye, James Odame, Yew, Chow Wenn, Ng, Oi-Wing, Monteil, Vanessa M, Mirazimi, Ali, Tan, Yee-Joo
• Format: Journal Article
• Language: English
• Published: England Portland Press Ltd 31.10.2018
• Subjects: A549 Cells; Chemokine CXCL10 - genetics; Coronavirus Infections - genetics; Coronavirus Infections - pathology; Coronavirus Infections - virology; Gene Expression Regulation, Viral - genetics; Host-Pathogen Interactions - genetics; Humans; Medicin och hälsovetenskap; Middle East Respiratory Syndrome Coronavirus - genetics; Middle East Respiratory Syndrome Coronavirus - pathogenicity; Nucleocapsid Proteins - genetics; Protein Domains - genetics; Transcriptional Activation - genetics; nucleocapsid; CXCL10; Middle East Respiratory Syndrome coronavirus
• ISSN: 0144-8463; 1573-4935; 1573-4935
• DOI: 10.1042/BSR20181059

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 , and , 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.