Role of heparan sulfate in the Zika virus entry, replication, and cell death
Role of heparan sulfate in the Zika virus entry, replication, and cell death
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DOI：
10.1016/j.virol.2019.01.019
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发表时间：
2019-03-01
期刊：
影响因子：
3.7
通讯作者：
Zhang, Ping
中科院分区：
文献类型：
--
作者：
Gao, Huixin;Lin, Yuxia;Zhang, Ping
寨卡病毒（ZIKV）是一种新发现的虫媒病毒，其感染与神经系统疾病密切相关。硫酸乙酰肝素（HS），许多病毒的附着因子，是否在ZIKV感染中发挥作用仍然存在争议。我们的研究通过使用CRISPR/Cas9系统破坏SLC 35 B2，B3 GAT 3或B4 GALT 7基因产生了几个HS生物合成缺陷细胞克隆。HS缺陷不影响ZIKV的病毒附着和内化，但减少登革病毒（DENY）2的附着。ZIKV和DENV 2的早期RNA和蛋白质水平在HS缺陷型细胞中受损，而病毒产量没有相应降低。我们的数据进一步显示HS促进由病毒感染诱导的细胞死亡，并且细胞死亡的抑制显著增加ZIKV和DENV 2的病毒复制。总的来说，我们的研究描述了HS在ZIKV诱导的病毒附着、复制和细胞死亡中的意想不到的作用。
Zika virus (ZIKV) is an emerging arbovirus and its infection associates with neurologic diseases. Whether heparan sulfate (HS), an attachment factor for many viruses, plays a role in the ZIKV infection remains controversial. Our study generated several HS biosynthesis-deficient cell clones by disrupting SLC35B2, B3GAT3, or B4GALT7 gene using the CRISPR/Cas9 system. The HS deficiency did not affect the viral attachment and internalization of ZIKV, but reduced the attachment of Dengue virus (DENY) 2. The early RNA and protein levels of ZIKV and DENV2 were impaired in the HS deficient cells, while the viral yields were not accordingly reduced. Our data further showed that HS promoted the cell death induced by virus infection, and inhibition of cell death significantly increased the viral replication of ZIKV and DENV2. Collectively, our study described an unexpected role of HS in the viral attachment, replication and cell death induced by ZIKV.