The roles of phosphatidylserine and its receptors in HIV replication

磷脂酰丝氨酸及其受体在HIV复制中的作用

• 批准号: 8602737
• 负责人: Koki Morizono
• 金额: $ 32.57万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-06-19 至 2017-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8602737
• 关键词: Antiviral Agents; Apoptosis; Apoptotic; Binding; CD209 gene; Cell membrane; Cells; Data; Dengue; Eating; Ectopic Expression; Excision; HIV; HIV Envelope Protein gp120; HIV Infections; HIV-1; Human; Immunoglobulins; Induction of Apoptosis; Infection; Lead; Lipids; Mediating; Membrane Proteins; Microbe; Molecular; Mucins; Mus; Phagocytes; Phagocytosis; Phosphatidylserines; Phospholipids; Pichinde; Play; Prevention therapy; Protein Binding; Proteins; Receptor Protein-Tyrosine Kinases; Research; Role; Ross river virus; Serum Proteins; Signal Transduction; Sindbis Virus; Supporting Cell; T-Lymphocyte; Th2 Cells; Vaccinia; Vaccinia virus; Vaccinium; Viral; Viral Envelope Proteins; Virion; Virus; Virus Diseases; axl receptor tyrosine kinase; cell type; env Gene Products; macrophage; novel; novel strategies; phosphatidylserine receptor; public health relevance; receptor; vector; viral envelope lipids; virus envelope; vpr Gene Products

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.

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 gp120 及其受体（包括 CD4 和 DC-SIGN）介导。因此，以往关于HIV结合的研究主要集中在gp120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其靶细胞上的受体结合并介导病毒附着。由于磷脂酰丝氨酸专门暴露在凋亡细胞上，因此磷脂酰丝氨酸受体通常用于吞噬细胞去除凋亡细胞。我们发现，一种特定类型的磷脂酰丝氨酸受体 TIM-1（在 CD4 阳性细胞上表达）也大大增强了 HIV 复制。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，以及巨噬细胞上表达的新发现的磷脂酰丝氨酸受体CD300a是否也可以支持HIV复制。我们还将研究艾滋病毒如何暴露病毒包膜上的磷脂酰丝氨酸。这些研究将为艾滋病毒复制机制开辟一条新途径，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。