Analysis of the macrophage membrane proteome: effects of viral infection

巨噬细胞膜蛋白质组分析：病毒感染的影响

基本信息

批准号：
8969989
负责人：
VERONICA SANCHEZ
金额：
$ 7.35万
依托单位：
UNIVERSITY OF ALABAMA AT BIRMINGHAM
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-05-19 至 2017-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8969989
关键词：
ATP binding cassette transporter 1 Acquired Immunodeficiency Syndrome Acute Adult Affect Age Antiviral Response Apoptosis Bacterial Infections Binding Biology CD36 gene Cardiovascular Diseases Cell membrane Cell physiology Cell surface Cells Cellular Stress Cholesterol Chronic Congenital Abnormality Cytomegalovirus Cytomegalovirus Infections Cytoplasm Disease Epidermal Growth Factor Receptor Fc Receptor Foam Cells Foundations Future Genes Global Change Goals Growth Factor Receptors HIV HIV Budding Herpesviridae Human Immunocompromised Host Infection Inflammation Inflammatory Influenza Interferons Investigation LOX gene Lipids Lipoprotein Binding Lipoproteins Malignant Neoplasms Mass Spectrum Analysis Measures Mediating Membrane Membrane Fluidity Membrane Lipids Membrane Microdomains Membrane Protein Traffic Metabolism Mus Mycoses Myeloid Cells Organ Transplantation PDGFRB gene Pathology Pathway interactions Patients Pattern recognition receptor Phagocytosis Phase Process Proteins Proteome Regulation Reporting Risk Role SR-BI receptor Signal Transduction Sphingolipids Stress Surface Transplant Recipients Viral Virion Virus Virus Diseases Work cholesterol transporters latent infection lipid metabolism lipid transport macrophage microbial monocyte oxidized low density lipoprotein pathogen public health relevance receptor receptor function research study response scavenger receptor uptake viperin

项目摘要

DESCRIPTION (provided by applicant): HCMV is beta-herpesvirus and is maintained for the lifetime of the infected host as a persistent infection. Historically, infection with this virus poes a threat to the immunocompromised, including patients with AIDS and those receiving organ transplants. The virus is ubiquitous and most adults are infected by age 40. In the healthy host, the acute phase of infection is self-limiting and the virus establishes a latent infection that can be reactivated in response to a variety of cellular stresses. Cells of the myeloid lineage are the reservoir for the virus. HCMV infection induces chronic inflammation; thus, the role of HCMV persistence in the pathology of diseases with inflammatory components, such as cardiovascular disease and cancer, is the focus of many studies. HCMV acquires a lipid envelope in the cytoplasm of infected cells but little is known about the effects of infection on lipid metabolism and trafficking. We have previously shown that infection blocked the conversion of THP-1 derived macrophages into lipid-laden foam cells in response to treatment with oxidized LDL. Subsequently, we observed that the virus inhibited the ability of cells to bind the lipoprotein, an interaction mediated by scavenger receptors on the cell surface. Our studies indicate that infection likely disrupts lipid raft microdomains on the plasma membrane and thereby inhibits scavenger receptor functions. The ultimate goal of this project is to understand the mechanisms that control lipid raft stability and scavenger receptor function in HCMV- infected cells. To accomplish this goal we will investigate changes in plasma membrane composition after infection and determine the roles of viperin, ABCA1, and SR-BI in regulation of receptor activity through their effects on lipid raft stability. The present studies will provide the foundation for future work.

描述（由适用提供）：HCMV是β-疱疹病毒，并在感染宿主的寿命中维持为持续感染。从历史上看，这种病毒感染对免疫功能低下的威胁，包括艾滋病患者和接受器官移植的患者。该病毒无处不在，大多数成年人被40岁的人感染。在健康宿主中，急性感染是自限制的，病毒会建立一种潜在的感染，可以响应各种细胞应激而重新激活。髓样谱系的细胞是病毒的储备。 HCMV感染诱导慢性感染；因此，HCMV持久性在炎性成分（例如心血管疾病和癌症）疾病的病理学中的作用是许多研究的重点。 HCMV在感染细胞的细胞质中获得了脂质包膜，但对感染对脂质代谢和运输的影响知之甚少。我们先前已经表明，感染阻止了THP-1衍生的巨噬细胞转化为载有脂质的泡沫细胞，以响应用氧化的LDL处理。随后，我们观察到病毒抑制了细胞结合脂蛋白的能力，A 通过清道夫受体在细胞表面介导的相互作用。我们的研究表明，感染可能会破坏质膜上的脂质筏微域，从而抑制清道夫受体功能。该项目的最终目标是了解控制脂质筏稳定性和清除剂受体功能的机制。为了实现这一目标，我们将通过感染后的质膜组成的变化，并通过对脂质筏稳定性的影响来确定耐蛋白，ABCA1和SR-BI在受体活性调节中的作用。本研究将为将来的工作奠定基础。