Zika virus promotes CCN1 expression via the CaMKIIα-CREB pathway in astrocytes
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 th...
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Taylor & Francis Group
2020
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oai:doaj.org-article:961d278ff52540e9af28159919520ae02021-11-17T14:21:57ZZika virus promotes CCN1 expression via the CaMKIIα-CREB pathway in astrocytes2150-55942150-560810.1080/21505594.2020.1715189https://doaj.org/article/961d278ff52540e9af28159919520ae02020-12-01T00:00:00Zhttp://dx.doi.org/10.1080/21505594.2020.1715189https://doaj.org/toc/2150-5594https://doaj.org/toc/2150-5608Zika 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.Jianhong SunWanpo ZhangZhongyuan TanCaishang ZhengYan TangXianliang KeYuan ZhangYan LiuPenghui LiQinxue HuHanzhong WangPanyong MaoZhenhua ZhengTaylor & Francis Grouparticlezika virusconnective tissue growth factor/nephroblastoma overexpressed (ccn) gene family 1(ccn1)ca2+/calmodulin-dependent protein kinase iicamp-responsive element-binding protein (creb)camp response elementns3 proteinInfectious and parasitic diseasesRC109-216ENVirulence, Vol 11, Iss 1, Pp 113-131 (2020) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
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 Infectious and parasitic diseases RC109-216 |
| spellingShingle |
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 Infectious and parasitic diseases RC109-216 Jianhong Sun Wanpo Zhang Zhongyuan Tan Caishang Zheng Yan Tang Xianliang Ke Yuan Zhang Yan Liu Penghui Li Qinxue Hu Hanzhong Wang Panyong Mao Zhenhua Zheng Zika virus promotes CCN1 expression via the CaMKIIα-CREB pathway in astrocytes |
| description |
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. |
| format |
article |
| author |
Jianhong Sun Wanpo Zhang Zhongyuan Tan Caishang Zheng Yan Tang Xianliang Ke Yuan Zhang Yan Liu Penghui Li Qinxue Hu Hanzhong Wang Panyong Mao Zhenhua Zheng |
| author_facet |
Jianhong Sun Wanpo Zhang Zhongyuan Tan Caishang Zheng Yan Tang Xianliang Ke Yuan Zhang Yan Liu Penghui Li Qinxue Hu Hanzhong Wang Panyong Mao Zhenhua Zheng |
| author_sort |
Jianhong Sun |
| title |
Zika virus promotes CCN1 expression via the CaMKIIα-CREB pathway in astrocytes |
| title_short |
Zika virus promotes CCN1 expression via the CaMKIIα-CREB pathway in astrocytes |
| title_full |
Zika virus promotes CCN1 expression via the CaMKIIα-CREB pathway in astrocytes |
| title_fullStr |
Zika virus promotes CCN1 expression via the CaMKIIα-CREB pathway in astrocytes |
| title_full_unstemmed |
Zika virus promotes CCN1 expression via the CaMKIIα-CREB pathway in astrocytes |
| title_sort |
zika virus promotes ccn1 expression via the camkiiα-creb pathway in astrocytes |
| publisher |
Taylor & Francis Group |
| publishDate |
2020 |
| url |
https://doaj.org/article/961d278ff52540e9af28159919520ae0 |
| work_keys_str_mv |
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