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

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)...

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Autores principales: Aboagye, James Odame, Yew, Chow Wenn, Ng, Oi-Wing, Monteil, Vanessa M., Mirazimi, Ali, Tan, Yee-Joo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Portland Press Ltd. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6200698/
https://www.ncbi.nlm.nih.gov/pubmed/30242057
http://dx.doi.org/10.1042/BSR20181059
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author Aboagye, James Odame
Yew, Chow Wenn
Ng, Oi-Wing
Monteil, Vanessa M.
Mirazimi, Ali
Tan, Yee-Joo
author_facet Aboagye, James Odame
Yew, Chow Wenn
Ng, Oi-Wing
Monteil, Vanessa M.
Mirazimi, Ali
Tan, Yee-Joo
author_sort Aboagye, James Odame
collection PubMed
description 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.
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spelling pubmed-62006982018-11-07 Overexpression of the nucleocapsid protein of Middle East respiratory syndrome coronavirus up-regulates CXCL10 Aboagye, James Odame Yew, Chow Wenn Ng, Oi-Wing Monteil, Vanessa M. Mirazimi, Ali Tan, Yee-Joo Biosci Rep Research Articles 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. Portland Press Ltd. 2018-10-17 /pmc/articles/PMC6200698/ /pubmed/30242057 http://dx.doi.org/10.1042/BSR20181059 Text en © 2018 The Author(s). http://creativecommons.org/licenses/by/4.0/This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY) (http://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Articles
Aboagye, James Odame
Yew, Chow Wenn
Ng, Oi-Wing
Monteil, Vanessa M.
Mirazimi, Ali
Tan, Yee-Joo
Overexpression of the nucleocapsid protein of Middle East respiratory syndrome coronavirus up-regulates CXCL10
title Overexpression of the nucleocapsid protein of Middle East respiratory syndrome coronavirus up-regulates CXCL10
title_full Overexpression of the nucleocapsid protein of Middle East respiratory syndrome coronavirus up-regulates CXCL10
title_fullStr Overexpression of the nucleocapsid protein of Middle East respiratory syndrome coronavirus up-regulates CXCL10
title_full_unstemmed Overexpression of the nucleocapsid protein of Middle East respiratory syndrome coronavirus up-regulates CXCL10
title_short Overexpression of the nucleocapsid protein of Middle East respiratory syndrome coronavirus up-regulates CXCL10
title_sort overexpression of the nucleocapsid protein of middle east respiratory syndrome coronavirus up-regulates cxcl10
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6200698/
https://www.ncbi.nlm.nih.gov/pubmed/30242057
http://dx.doi.org/10.1042/BSR20181059
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