The roles of phosphatidylserine and its receptors in HIV replication

描述（由申请人提供）：病毒感染的第一步是将病毒与目标细胞结合。HIV的结合通常由病毒包膜蛋白gp120及其受体介导，包括CD4和DC-SIGN。因此，以往对HIV结合的研究主要集中在gp120与其受体的相互作用上。我们最近发现了一种与包膜蛋白无关的病毒结合方式。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暴露在凋亡细胞上，因此磷脂酰丝氨酸受体通常用于吞噬细胞清除凋亡细胞。我们发现，在cd4阳性细胞上表达的一种特定类型的磷脂酰丝氨酸受体TIM-1也显著增强了HIV的复制。在本研究中，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，以及巨噬细胞上表达的新发现的磷脂酰丝氨酸受体CD300a是否也能支持HIV复制。我们还将研究HIV如何在病毒包膜上暴露磷脂酰丝氨酸。这些研究将为研究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.