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Zika virus promotes CCN1 expression via the CaMKIIα-CREB pathway in astrocytes.

Sun, J; Zhang, W; Tan, Z; Zheng, C; Tang, Y; Ke, X; Zhang, Y; Liu, Y; Li, P; Hu, Q; et al. Sun, J; Zhang, W; Tan, Z; Zheng, C; Tang, Y; Ke, X; Zhang, Y; Liu, Y; Li, P; Hu, Q; Wang, H; Mao, P; Zheng, Z (2020) Zika virus promotes CCN1 expression via the CaMKIIα-CREB pathway in astrocytes. Virulence, 11 (1). pp. 113-131. ISSN 2150-5608 https://doi.org/10.1080/21505594.2020.1715189
SGUL Authors: Hu, Qinxue

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Abstract

Zika virus (ZIKV) infection in the human central nervous system (CNS) causes Guillain-Barre syndrome, cerebellum deformity, and other diseases. Astrocytes are immune response cells in the CNS and an important component of the blood-brain barrier. Consequently, any damage to astrocytes facilitates the spread of ZIKV in the CNS. Connective tissue growth factor/Nephroblastoma overexpressed gene family 1 (CCN1), an important inflammatory factor secreted by astrocytes, is reported to regulate innate immunity and viral infection. However, the mechanism by which astrocyte viral infection affects CCN1 expression remains undefined. In this study, we demonstrate that ZIKV infection up-regulates CCN1 expression in astrocytes, thus promoting intracellular viral replication. Other studies revealed that the cAMP response element (CRE) in the CCN1 promoter is activated by the ZIKV NS3 protein. The cAMP-responsive element-binding protein (CREB), a transacting factor of the CRE, is also activated by NS3 or ZIKV. Furthermore,a specific inhibitor of CREB, i.e. SGC-CBP30, reduced ZIKV-induced CCN1 up-regulation and ZIKV replication. Moreover, co-immunoprecipitation, overexpression, and knockdown studies confirmed that the interaction between NS3 and the regulatory domain of CaMKIIα could activate the CREB pathway, thus resulting in the up-regulation of CCN1 expression and enhancement of virus replication. In conclusion, the findings of our investigations on the NS3-CaMKIIα-CREB-CCN1 pathway provide a foundation for understanding the infection mechanism of ZIKV in the CNS.

Item Type: Article
Additional Information: © 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Keywords: Zika virus, cAMP response element, cAMP-responsive element-binding protein (CREB), ca2+/calmodulin-dependent protein kinase II, connective tissue growth factor/Nephroblastoma overexpressed (CCN) gene family 1(CCN1), ns3 protein, Zika virus, connective tissue growth factor/Nephroblastoma overexpressed (CCN) gene family 1(CCN1), ca2+/calmodulin-dependent protein kinase II, cAMP-responsive element-binding protein (CREB), cAMP response element, ns3 protein
SGUL Research Institute / Research Centre: Academic Structure > Infection and Immunity Research Institute (INII)
Journal or Publication Title: Virulence
ISSN: 2150-5608
Language: eng
Dates:
DateEvent
20 January 2020Published
22 November 2019Accepted
Publisher License: Creative Commons: Attribution 4.0
Projects:
Project IDFunderFunder ID
81672036National Natural Science Foundation of Chinahttp://dx.doi.org/10.13039/501100001809
2016302Youth Innovation Promotion Association of the Chinese Academy of Scienceshttp://dx.doi.org/10.13039/501100004739
2018YFA0507201National Key R&D Program of ChinaUNSPECIFIED
PubMed ID: 31957543
Web of Science ID: WOS:000508872800001
Go to PubMed abstract
URI: http://openaccess.sgul.ac.uk/id/eprint/111756
Publisher's version: https://doi.org/10.1080/21505594.2020.1715189

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