The roles of phosphatidylserine and its receptors in HIV replication

描述（申请人提供）：病毒感染的第一步是病毒与其靶细胞结合。HIV的结合通常由病毒包膜蛋白gp 120及其受体（包括CD 4和DC-SIGN）介导。因此，以前的HIV结合研究主要集中在gp 120与其受体之间的相互作用。我们最近发现了一种不依赖于包膜蛋白的病毒结合方式.一种称为磷脂酰丝氨酸的病毒包膜脂质与靶细胞上的受体结合并介导病毒附着。由于磷脂酰丝氨酸特异性地暴露于凋亡细胞上，磷脂酰丝氨酸受体通常用于通过吞噬细胞去除凋亡细胞。我们发现，HIV复制也大大增强了一种特定类型的磷脂酰丝氨酸受体，TIM-1，这是表达在CD 4阳性细胞。在拟议的研究中，我们将研究包膜磷脂酰丝氨酸和TIM-1促进病毒复制的分子机制，以及CD 300 a（一种新发现的在巨噬细胞上表达的磷脂酰丝氨酸受体）是否也可以支持HIV复制。我们还将研究HIV如何暴露病毒包膜上的磷脂酰丝氨酸。这些研究将为HIV复制机制开辟新的途径，并有助于开发针对磷脂酰丝氨酸介导的病毒复制的新型抗病毒策略。

DESCRIPTION (provided by applicant): The first step of viral infection is binding of virus to its target cells. Binding of HIV is usually mediated by viral envelope proteins, gp120, and its receptors, including CD4 and DC-SIGN. Therefore, previous studies of HIV binding have mainly focused on the interaction between gp120 and their receptors. We have recently found an envelope- protein independent manner of virus binding. One type of viral envelope lipid called phosphatidylserine binds to its receptors on target cells and mediates virus attachment. Since phosphatidylserine is specifically exposed on apoptotic cells, phosphatidylserine receptors are typically used for removal of apoptotic cells by phagocytes. We found that HIV replication is also drastically enhanced by one specific type of phosphatidylserine receptor, TIM-1, which is expressed on CD4-positive cells. In the proposed studies, we will investigate the molecular mechanism by which envelope phosphatidylserine and TIM-1 facilitates viral replication and whether CD300a, which is a newly identified phosphatidylserine receptor expressed on macrophages, can also support HIV replication. We will also investigate how HIV exposes phosphatidylserine on viral envelope. These studies will open a new avenue in HIV replication mechanism and help develop novel antiviral strategies that target phosphatidylserine-mediated viral replication.