Song Da-Hoon, Garcia Gustavo, Situ Kathy, Chua Bernadette A, Hong Madeline Lauren O, Do Elyza A, Ramirez Christina M, Harui Airi, Arumugaswami Vaithilingaraja, Morizono Kouki
Division of Hematology and Oncology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA; UCLA AIDS Institute, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA.
Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA, 90095, USA.
Virology. 2021 Aug;560:17-33. doi: 10.1016/j.virol.2021.04.013. Epub 2021 May 10.
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.
包膜磷脂酰丝氨酸（PtdSer）和磷脂酰乙醇胺（PtdEtr）已被证明可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并不能阻断PtdSer介导的病毒感染。缺乏能够掩盖包膜PtdSer和PtdEtr并随后抑制感染的试剂阻碍了对包膜磷脂在病毒感染中作用的阐明。在此，我们开发了sTIM1dMLDR801，一种能够阻断包膜病毒依赖PtdSer和PtdEtr的感染的试剂。使用sTIM1dMLDR801，我们发现包膜PtdSer和/或PtdEtr不仅可以支持寨卡病毒感染人类细胞，还能支持其感染蚊子细胞。在寨卡病毒感染的小鼠模型中，sTIM1dMLDR801降低了血清和脾脏中的寨卡病毒载量，表明包膜PtdSer和/或PtdEtr在体内病毒感染中发挥支持作用。sTIM1dMLDR801将有助于阐明包膜PtdSer和PtdEtr在各种病毒物种感染中的作用，从而促进其受体和传播机制的鉴定。
