Dysregulation of Ephrin receptor and PPAR signaling pathways in neural progenitor cells infected by Zika virus

Zika virus (ZIKV) infection is a serious public threat with cases reported in about 70 countries and territories. One of the most serious consequences of ZIKV infection is congenital microcephaly in babies. Congenital microcephaly has been suggested to result from infection of neural progenitor cell...

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Main Authors: Sathya N. Thulasi Raman, Elyse Latreille, Jun Gao, Wanyue Zhang, Jianguo Wu, Marsha S. Russell, Lisa Walrond, Terry Cyr, Jessie R. Lavoie, David Safronetz, Jingxin Cao, Simon Sauve, Aaron Farnsworth, Wangxue Chen, Pei-Yong Shi, Youchun Wang, Lisheng Wang, Michael Rosu-Myles, Xuguang Li
Format: Article
Language:English
Published: Taylor & Francis Group 2020-01-01
Series:Emerging Microbes and Infections
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Online Access:https://www.tandfonline.com/doi/10.1080/22221751.2020.1818631
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author Sathya N. Thulasi Raman
Elyse Latreille
Jun Gao
Wanyue Zhang
Jianguo Wu
Marsha S. Russell
Lisa Walrond
Terry Cyr
Jessie R. Lavoie
David Safronetz
Jingxin Cao
Simon Sauve
Aaron Farnsworth
Wangxue Chen
Pei-Yong Shi
Youchun Wang
Lisheng Wang
Michael Rosu-Myles
Xuguang Li
author_facet Sathya N. Thulasi Raman
Elyse Latreille
Jun Gao
Wanyue Zhang
Jianguo Wu
Marsha S. Russell
Lisa Walrond
Terry Cyr
Jessie R. Lavoie
David Safronetz
Jingxin Cao
Simon Sauve
Aaron Farnsworth
Wangxue Chen
Pei-Yong Shi
Youchun Wang
Lisheng Wang
Michael Rosu-Myles
Xuguang Li
author_sort Sathya N. Thulasi Raman
collection DOAJ
description Zika virus (ZIKV) infection is a serious public threat with cases reported in about 70 countries and territories. One of the most serious consequences of ZIKV infection is congenital microcephaly in babies. Congenital microcephaly has been suggested to result from infection of neural progenitor cells (NPCs) in the developing fetal brain. However, the molecular and cellular mechanisms underlying microcephaly development remains to be fully elucidated. In this study, we employed quantitative proteomics to determine protein expression profile that occur during viral replication in NPCs. Bioinformatics analysis of the protein expression changes resulted in the identification of a wide range of cell signaling pathways. Specifically, pathways involved in neurogenesis and embryonic development were markedly altered, along with those associated with cell cycle, apoptosis, lipid metabolism and oxidative stress. Notably, the differential regulation of Ephrin Receptor and PPAR signaling pathways, as revealed by quantitative proteomics and validated by qPCR array, underscores the need to explore these pathways in disease development. Collectively, these results indicate that ZIKV-induced pathogenesis involves complex virus-host reactions; the findings reported here could help shed light on the mechanisms underlying ZIKV-induced microcephaly and ZIKV replication in NPCs.
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spelling doaj-art-fdad955415bd458c92d94ba2bdcf4fe12025-08-20T02:16:09ZengTaylor & Francis GroupEmerging Microbes and Infections2222-17512020-01-01912046206010.1080/22221751.2020.1818631Dysregulation of Ephrin receptor and PPAR signaling pathways in neural progenitor cells infected by Zika virusSathya N. Thulasi Raman0Elyse Latreille1Jun Gao2Wanyue Zhang3Jianguo Wu4Marsha S. Russell5Lisa Walrond6Terry Cyr7Jessie R. Lavoie8David Safronetz9Jingxin Cao10Simon Sauve11Aaron Farnsworth12Wangxue Chen13Pei-Yong Shi14Youchun Wang15Lisheng Wang16Michael Rosu-Myles17Xuguang Li18Centre for Biologics Evaluation, Biologics and Radiopharmaceutical Drugs Directorate, HPFB, Health Canada and WHO Collaborating Centre for Standardization and Evaluation of Biologicals, Ottawa, ON, CanadaCentre for Biologics Evaluation, Biologics and Radiopharmaceutical Drugs Directorate, HPFB, Health Canada and WHO Collaborating Centre for Standardization and Evaluation of Biologicals, Ottawa, ON, CanadaCentre for Biologics Evaluation, Biologics and Radiopharmaceutical Drugs Directorate, HPFB, Health Canada and WHO Collaborating Centre for Standardization and Evaluation of Biologicals, Ottawa, ON, CanadaCentre for Biologics Evaluation, Biologics and Radiopharmaceutical Drugs Directorate, HPFB, Health Canada and WHO Collaborating Centre for Standardization and Evaluation of Biologicals, Ottawa, ON, CanadaCentre for Biologics Evaluation, Biologics and Radiopharmaceutical Drugs Directorate, HPFB, Health Canada and WHO Collaborating Centre for Standardization and Evaluation of Biologicals, Ottawa, ON, CanadaCentre for Biologics Evaluation, Biologics and Radiopharmaceutical Drugs Directorate, HPFB, Health Canada and WHO Collaborating Centre for Standardization and Evaluation of Biologicals, Ottawa, ON, CanadaCentre for Biologics Evaluation, Biologics and Radiopharmaceutical Drugs Directorate, HPFB, Health Canada and WHO Collaborating Centre for Standardization and Evaluation of Biologicals, Ottawa, ON, CanadaCentre for Biologics Evaluation, Biologics and Radiopharmaceutical Drugs Directorate, HPFB, Health Canada and WHO Collaborating Centre for Standardization and Evaluation of Biologicals, Ottawa, ON, CanadaCentre for Biologics Evaluation, Biologics and Radiopharmaceutical Drugs Directorate, HPFB, Health Canada and WHO Collaborating Centre for Standardization and Evaluation of Biologicals, Ottawa, ON, CanadaNational Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB, CanadaNational Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB, CanadaCentre for Biologics Evaluation, Biologics and Radiopharmaceutical Drugs Directorate, HPFB, Health Canada and WHO Collaborating Centre for Standardization and Evaluation of Biologicals, Ottawa, ON, CanadaCentre for Biologics Evaluation, Biologics and Radiopharmaceutical Drugs Directorate, HPFB, Health Canada and WHO Collaborating Centre for Standardization and Evaluation of Biologicals, Ottawa, ON, CanadaNational Research Council of Canada, Human Health Therapeutics, Ottawa, ON, CanadaDepartment of Biochemistry & Molecular Biology, University of Texas Medical Branch, Galveston, TX, USANational Institute for Food and Drug Control and WHO Collaborating Center for Standardization and Evaluation of Biologicals, Beijing, People’s Republic of ChinaDepartment of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON, CanadaCentre for Biologics Evaluation, Biologics and Radiopharmaceutical Drugs Directorate, HPFB, Health Canada and WHO Collaborating Centre for Standardization and Evaluation of Biologicals, Ottawa, ON, CanadaCentre for Biologics Evaluation, Biologics and Radiopharmaceutical Drugs Directorate, HPFB, Health Canada and WHO Collaborating Centre for Standardization and Evaluation of Biologicals, Ottawa, ON, CanadaZika virus (ZIKV) infection is a serious public threat with cases reported in about 70 countries and territories. One of the most serious consequences of ZIKV infection is congenital microcephaly in babies. Congenital microcephaly has been suggested to result from infection of neural progenitor cells (NPCs) in the developing fetal brain. However, the molecular and cellular mechanisms underlying microcephaly development remains to be fully elucidated. In this study, we employed quantitative proteomics to determine protein expression profile that occur during viral replication in NPCs. Bioinformatics analysis of the protein expression changes resulted in the identification of a wide range of cell signaling pathways. Specifically, pathways involved in neurogenesis and embryonic development were markedly altered, along with those associated with cell cycle, apoptosis, lipid metabolism and oxidative stress. Notably, the differential regulation of Ephrin Receptor and PPAR signaling pathways, as revealed by quantitative proteomics and validated by qPCR array, underscores the need to explore these pathways in disease development. Collectively, these results indicate that ZIKV-induced pathogenesis involves complex virus-host reactions; the findings reported here could help shed light on the mechanisms underlying ZIKV-induced microcephaly and ZIKV replication in NPCs.https://www.tandfonline.com/doi/10.1080/22221751.2020.1818631Neural progenitor cellsZIKVEphrin signalingPPAR signalingproteomicsingenuity pathway analysis
spellingShingle Sathya N. Thulasi Raman
Elyse Latreille
Jun Gao
Wanyue Zhang
Jianguo Wu
Marsha S. Russell
Lisa Walrond
Terry Cyr
Jessie R. Lavoie
David Safronetz
Jingxin Cao
Simon Sauve
Aaron Farnsworth
Wangxue Chen
Pei-Yong Shi
Youchun Wang
Lisheng Wang
Michael Rosu-Myles
Xuguang Li
Dysregulation of Ephrin receptor and PPAR signaling pathways in neural progenitor cells infected by Zika virus
Emerging Microbes and Infections
Neural progenitor cells
ZIKV
Ephrin signaling
PPAR signaling
proteomics
ingenuity pathway analysis
title Dysregulation of Ephrin receptor and PPAR signaling pathways in neural progenitor cells infected by Zika virus
title_full Dysregulation of Ephrin receptor and PPAR signaling pathways in neural progenitor cells infected by Zika virus
title_fullStr Dysregulation of Ephrin receptor and PPAR signaling pathways in neural progenitor cells infected by Zika virus
title_full_unstemmed Dysregulation of Ephrin receptor and PPAR signaling pathways in neural progenitor cells infected by Zika virus
title_short Dysregulation of Ephrin receptor and PPAR signaling pathways in neural progenitor cells infected by Zika virus
title_sort dysregulation of ephrin receptor and ppar signaling pathways in neural progenitor cells infected by zika virus
topic Neural progenitor cells
ZIKV
Ephrin signaling
PPAR signaling
proteomics
ingenuity pathway analysis
url https://www.tandfonline.com/doi/10.1080/22221751.2020.1818631
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