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

基本信息

批准号：
8685123
负责人：
Koki Morizono
金额：
$ 34.65万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
依托单位国家：
美国
项目类别：
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/8685123
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

项目摘要

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（由申请人提供）：病毒感染的第一步是病毒与其靶细胞结合。 HIV的结合通常是由病毒包膜蛋白GP120及其受体（包括CD4和DC-SIGN）介导的。因此，先前对HIV结合的研究主要集中在GP120及其受体之间的相互作用上。我们最近发现了一种独立的病毒结合方式。一种称为磷脂酰丝氨酸的病毒包膜脂质在靶细胞上与其受体结合，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，以及在巨噬细胞上表达的新近鉴定的磷脂酰敏素受体的CD300A是否也可以支持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。这些研究将开放新的HIV复制机制的途径，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。