Molecular characterization of cellular stress responses during coronavirus infection

Coronaviruses are important animal and human pathogens. In this study, two stress pathways – the unfolded protein response (UPR) and c-Jun N-terminal kinase (JNK) pathway are shown to be activated in cells infected with infectious bronchitis virus (IBV). The inositol requiring protein 1 (IRE1) branc...

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Main Author: Fung, To Sing
Other Authors: Liu Ding Xiang
Format: Thesis
Language:English
Published: 2015
Subjects:
Online Access:http://hdl.handle.net/10356/63947
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author Fung, To Sing
author2 Liu Ding Xiang
author_facet Liu Ding Xiang
Fung, To Sing
author_sort Fung, To Sing
collection NTU
description Coronaviruses are important animal and human pathogens. In this study, two stress pathways – the unfolded protein response (UPR) and c-Jun N-terminal kinase (JNK) pathway are shown to be activated in cells infected with infectious bronchitis virus (IBV). The inositol requiring protein 1 (IRE1) branch of UPR protects infected cells from apoptosis by splicing the mRNA of X-box protein 1 (XBP1) and differentially modulating the activation of two kinases. The PKR-like ER protein kinase (PERK) branch of UPR promotes IBV-induced apoptosis by up-regulating C/EBP homologous protein (CHOP). JNK is phosphorylated by MKK7 during IBV infection, and it promotes apoptosis by modulating the level of B cell lymphoma-2 (Bcl2) family proteins. Moreover, IRE1 mediates autophagy induction whereas XBP1 and JNK contribute to the induction of pro-inflammatory cytokines (interleukin-8) and type-I interferon in the IBV-infected cells. Therefore, these stress pathways modulate critical cellular events and contribute to pathogenesis during coronavirus infection.
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spelling ntu-10356/639472023-02-28T18:31:02Z Molecular characterization of cellular stress responses during coronavirus infection Fung, To Sing Liu Ding Xiang School of Biological Sciences DRNTU::Science::Biological sciences::Microbiology::Virology Coronaviruses are important animal and human pathogens. In this study, two stress pathways – the unfolded protein response (UPR) and c-Jun N-terminal kinase (JNK) pathway are shown to be activated in cells infected with infectious bronchitis virus (IBV). The inositol requiring protein 1 (IRE1) branch of UPR protects infected cells from apoptosis by splicing the mRNA of X-box protein 1 (XBP1) and differentially modulating the activation of two kinases. The PKR-like ER protein kinase (PERK) branch of UPR promotes IBV-induced apoptosis by up-regulating C/EBP homologous protein (CHOP). JNK is phosphorylated by MKK7 during IBV infection, and it promotes apoptosis by modulating the level of B cell lymphoma-2 (Bcl2) family proteins. Moreover, IRE1 mediates autophagy induction whereas XBP1 and JNK contribute to the induction of pro-inflammatory cytokines (interleukin-8) and type-I interferon in the IBV-infected cells. Therefore, these stress pathways modulate critical cellular events and contribute to pathogenesis during coronavirus infection. ​Doctor of Philosophy (SBS) 2015-05-20T08:12:34Z 2015-05-20T08:12:34Z 2015 2015 Thesis Fung, T. S. (2015). Molecular characterization of cellular stress responses during coronavirus infection. Doctoral thesis, Nanyang Technological University, Singapore. http://hdl.handle.net/10356/63947 en 232 p. application/pdf
spellingShingle DRNTU::Science::Biological sciences::Microbiology::Virology
Fung, To Sing
Molecular characterization of cellular stress responses during coronavirus infection
title Molecular characterization of cellular stress responses during coronavirus infection
title_full Molecular characterization of cellular stress responses during coronavirus infection
title_fullStr Molecular characterization of cellular stress responses during coronavirus infection
title_full_unstemmed Molecular characterization of cellular stress responses during coronavirus infection
title_short Molecular characterization of cellular stress responses during coronavirus infection
title_sort molecular characterization of cellular stress responses during coronavirus infection
topic DRNTU::Science::Biological sciences::Microbiology::Virology
url http://hdl.handle.net/10356/63947
work_keys_str_mv AT fungtosing molecularcharacterizationofcellularstressresponsesduringcoronavirusinfection