Development of a blocker of the universal phosphatidylserine- and phosphatidylethanolamine-dependent viral entry pathways.

Development of a blocker of the universal phosphatidylserine- and phosphatidylethanolamine-dependent viral entry pathways.
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DOI:
10.1016/j.virol.2021.04.013
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发表时间:
2021-08
期刊:
影响因子:
3.7
通讯作者:
Morizono K
Morizono K
中科院分区:
医学3区
文献类型:
--
作者:
Song DH;Garcia G Jr;Situ K;Chua BA;Hong MLO;Do EA;Ramirez CM;Harui A;Arumugaswami V;Morizono K

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包膜磷脂酰丝氨酸(PtdSer)和磷脂酰乙醇胺(PtdEtr)已被证明介导包膜病毒的结合。然而,常用的PtdSer结合分子如膜联蛋白V不能阻断PtdSer介导的病毒感染。缺乏可以隐藏包膜PtdSer和PtdEtr并随后抑制感染的试剂阻碍了包膜磷脂在病毒感染中的作用的阐明。在这里,我们开发了sTIM 1dMLDR 801,一种能够阻断包膜病毒的PtdSer和PtdEtr依赖性感染的试剂。使用sTIMldMLDR 801,我们发现包膜PtdSer和/或PtdEtr不仅可以支持人细胞的ZIKV感染,还可以支持蚊子细胞的ZIKV感染。在ZIKV感染的小鼠模型中,sTIMldMLDR 801降低血清和脾脏中的ZIKV负荷,表明包膜PtdSer和/或PtdEtr支持体内病毒感染。sTIM 1dMLDR 801将能够阐明包膜PtdSer和PtdEtr在各种病毒种感染中的作用,从而促进其受体和传播机制的鉴定。
Envelope phosphatidylserine (PtdSer) and phosphatidylethanolamine (PtdEtr) have been shown to mediate binding of enveloped viruses. However, commonly used PtdSer binding molecules such as Annexin V cannot block PtdSer-mediated viral infection. Lack of reagents that can conceal envelope PtdSer and PtdEtr and subsequently inhibit infection hinders elucidation of the roles of the envelope phospholipids in viral infection. Here, we developed sTIM1dMLDR801, a reagent capable of blocking PtdSer- and PtdEtr- dependent infection of enveloped viruses. Using sTIM1dMLDR801, we found that envelope PtdSer and/or PtdEtr can support ZIKV infection of not only human but also mosquito cells. In a mouse model for ZIKV infection, sTIM1dMLDR801 reduced ZIKV load in serum and the spleen, indicating envelope PtdSer and/or PtdEtr support in viral infection in vivo. sTIM1dMLDR801 will enable elucidation of the roles of envelope PtdSer and PtdEtr in infection of various virus species, thereby facilitating identification of their receptors and transmission mechanisms.
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