Placental Alkaline Phosphatase Promotes Zika Virus Replication by Stabilizing Viral Proteins through BIP

ABSTRACT Zika virus (ZIKV) infection during pregnancy causes intrauterine growth defects and microcephaly, but knowledge of the mechanism through which ZIKV infects and replicates in the placenta remains elusive. Here, we found that ALPP, an alkaline phosphatase expressed primarily in placental tiss...

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Main Authors:	Jian Chen, Zhilu Chen, Mingbin Liu, Tianyi Qiu, Daobin Feng, Chen Zhao, Shuye Zhang, Xiaoyan Zhang, Jianqing Xu
Format:	article
Language:	EN
Published:	American Society for Microbiology 2020
Subjects:	BIP placental alkaline phosphatase Zika virus placental trophoblast cells Microbiology QR1-502
Online Access:	https://doaj.org/article/cb390dce90b1421a9e50dfc2071cf9b1
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spelling	oai:doaj.org-article:cb390dce90b1421a9e50dfc2071cf9b12021-11-15T16:19:09ZPlacental Alkaline Phosphatase Promotes Zika Virus Replication by Stabilizing Viral Proteins through BIP10.1128/mBio.01716-202150-7511https://doaj.org/article/cb390dce90b1421a9e50dfc2071cf9b12020-10-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01716-20https://doaj.org/toc/2150-7511ABSTRACT Zika virus (ZIKV) infection during pregnancy causes intrauterine growth defects and microcephaly, but knowledge of the mechanism through which ZIKV infects and replicates in the placenta remains elusive. Here, we found that ALPP, an alkaline phosphatase expressed primarily in placental tissue, promoted ZIKV infection in both human placental trophoblasts and astrocytoma cells. ALPP bound to ZIKV structural and nonstructural proteins and thereby prevented their proteasome-mediated degradation and enhanced viral RNA replication and virion biogenesis. In addition, the function of ALPP in ZIKV infection depends on its phosphatase activity. Furthermore, we demonstrated that ALPP was stabilized through interactions with BIP, which is the endoplasmic reticulum (ER)-resident heat shock protein 70 chaperone. The chaperone activity of BIP promoted ZIKV infection and mediated the interaction between ALPP and ZIKV proteins. Collectively, our findings reveal a previously unrecognized mechanism through which ALPP facilitates ZIKV replication by coordinating with the BIP protein. IMPORTANCE ZIKV is a recently emerged mosquito-borne flavivirus that can cause devastating congenital Zika syndrome in pregnant women and Guillain-Barré syndrome in adults, but how ZIKV specifically targets the placenta is not well understood. Here, we identified an alkaline phosphatase (ALPP) that is expressed primarily in placental tissue and promotes ZIKV infection by colocalizing with ZIKV proteins and preventing their proteasome-mediated degradation. The phosphatase activity of ALPP could be required for optimal ZIKV infection, and ALPP is stabilized by BIP via its chaperone activity. This report provides novel insights into host factors required for ZIKV infection, which potentially has implications for ZIKV infection of the placenta.Jian ChenZhilu ChenMingbin LiuTianyi QiuDaobin FengChen ZhaoShuye ZhangXiaoyan ZhangJianqing XuAmerican Society for MicrobiologyarticleBIPplacental alkaline phosphataseZika virusplacental trophoblast cellsMicrobiologyQR1-502ENmBio, Vol 11, Iss 5 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	BIP placental alkaline phosphatase Zika virus placental trophoblast cells Microbiology QR1-502
spellingShingle	BIP placental alkaline phosphatase Zika virus placental trophoblast cells Microbiology QR1-502 Jian Chen Zhilu Chen Mingbin Liu Tianyi Qiu Daobin Feng Chen Zhao Shuye Zhang Xiaoyan Zhang Jianqing Xu Placental Alkaline Phosphatase Promotes Zika Virus Replication by Stabilizing Viral Proteins through BIP
description	ABSTRACT Zika virus (ZIKV) infection during pregnancy causes intrauterine growth defects and microcephaly, but knowledge of the mechanism through which ZIKV infects and replicates in the placenta remains elusive. Here, we found that ALPP, an alkaline phosphatase expressed primarily in placental tissue, promoted ZIKV infection in both human placental trophoblasts and astrocytoma cells. ALPP bound to ZIKV structural and nonstructural proteins and thereby prevented their proteasome-mediated degradation and enhanced viral RNA replication and virion biogenesis. In addition, the function of ALPP in ZIKV infection depends on its phosphatase activity. Furthermore, we demonstrated that ALPP was stabilized through interactions with BIP, which is the endoplasmic reticulum (ER)-resident heat shock protein 70 chaperone. The chaperone activity of BIP promoted ZIKV infection and mediated the interaction between ALPP and ZIKV proteins. Collectively, our findings reveal a previously unrecognized mechanism through which ALPP facilitates ZIKV replication by coordinating with the BIP protein. IMPORTANCE ZIKV is a recently emerged mosquito-borne flavivirus that can cause devastating congenital Zika syndrome in pregnant women and Guillain-Barré syndrome in adults, but how ZIKV specifically targets the placenta is not well understood. Here, we identified an alkaline phosphatase (ALPP) that is expressed primarily in placental tissue and promotes ZIKV infection by colocalizing with ZIKV proteins and preventing their proteasome-mediated degradation. The phosphatase activity of ALPP could be required for optimal ZIKV infection, and ALPP is stabilized by BIP via its chaperone activity. This report provides novel insights into host factors required for ZIKV infection, which potentially has implications for ZIKV infection of the placenta.
format	article
author	Jian Chen Zhilu Chen Mingbin Liu Tianyi Qiu Daobin Feng Chen Zhao Shuye Zhang Xiaoyan Zhang Jianqing Xu
author_facet	Jian Chen Zhilu Chen Mingbin Liu Tianyi Qiu Daobin Feng Chen Zhao Shuye Zhang Xiaoyan Zhang Jianqing Xu
author_sort	Jian Chen
title	Placental Alkaline Phosphatase Promotes Zika Virus Replication by Stabilizing Viral Proteins through BIP
title_short	Placental Alkaline Phosphatase Promotes Zika Virus Replication by Stabilizing Viral Proteins through BIP
title_full	Placental Alkaline Phosphatase Promotes Zika Virus Replication by Stabilizing Viral Proteins through BIP
title_fullStr	Placental Alkaline Phosphatase Promotes Zika Virus Replication by Stabilizing Viral Proteins through BIP
title_full_unstemmed	Placental Alkaline Phosphatase Promotes Zika Virus Replication by Stabilizing Viral Proteins through BIP
title_sort	placental alkaline phosphatase promotes zika virus replication by stabilizing viral proteins through bip
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/cb390dce90b1421a9e50dfc2071cf9b1
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Placental Alkaline Phosphatase Promotes Zika Virus Replication by Stabilizing Viral Proteins through BIP

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