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

开发通用的磷脂酰丝氨酸和磷脂酰乙醇胺依赖性病毒进入途径的阻断剂

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作者:Da-Hoon Song, Gustavo Garcia Jr, Kathy Situ, Bernadette A Chua, Madeline Lauren O Hong, Elyza A Do, Christina M Ramirez, Airi Harui, Vaithilingaraja Arumugaswami, Kouki Morizono

Abstract

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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