The impact of quasi-envelopment on hepatitis virus infection and immunity

准包封对肝炎病毒感染及免疫的影响

• 批准号: 9020571
• 负责人: Zongdi Feng
• 金额: $ 18.69万
• 依托单位: RESEARCH INST NATIONWIDE CHILDREN'S HOSP
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-01-06 至 2017-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9020571
• 关键词: Acute; Address; Antibodies; Binding; Biological Assay; Blood; Capsid; Capsid Proteins; Cells; Developed Countries; Developing Countries; Disease; Epidemic; Family Picornaviridae; Fc Receptor; Genes; Health Hazards; Hepatitis; Hepatitis A Virus; Hepatitis B; Hepatitis E; Hepatitis E virus; Hepatitis Viruses; Human; Immunity; Individual; Infection; Life Cycle Stages; Macaca mulatta; Maps; Membrane; Pathogenesis; Pathway interactions; Phosphatidylserines; Play; Population; Protein Family; Proteins; Public Health; Publishing; Research; Resistance; Role; Staging; Surface; Testing; Viral; Viral Antigens; Viral hepatitis; Virion; Virus; Virus Diseases; Work; extracellular; extracellular vesicles; foodborne; immunosuppressed; inhibitor/antagonist; knock-down; neutralizing antibody; novel; novel virus; particle; prevent; public health relevance; receptor; research study; seropositive; trafficking; uptake; viral transmission; virus pathogenesis

 DESCRIPTION (provided by applicant): Hepatitis A virus (HAV) and hepatitis E virus (HEV) infections are common causes of epidemic food-borne and water-borne hepatitis in under-developed regions of the world. Recently sporadic HEV infections have emerged as a significant public health hazard in well-developed countries. The recognition of zoonotic and blood-borne HEV transmission and its ability to persistent in immunosuppressed individuals is also alarming. Approximately 20% of the U.S. population is seropositive for HEV, indicating that HEV exposure is more common than previously thought. Although both recognized as non-enveloped viruses, recent studies show that HAV and HEV circulate in the blood as "quasi-enveloped" particles. These novel particles differ from classic enveloped viruses in that no viral antigens are present on the surface of their membrane, therefore are highly resistant to neutralizing antibodies. The impact of this "quasi-envelopment" on hepatitis virus life cycle, immunity, and pathogenesis is poorly understood. This proposal will explore the mechanisms by which quasi- enveloped HAV and HEV enter the cells and are neutralized by antibodies. Aim 1 will test the hypothesis that entry of "quasi-enveloped" HAV and HEV is through a cellular mechanism for extracellular vesicular uptake. Aim 2 will determine the mechanism of neutralization for quasi-enveloped HAV and HEV. Completion of these aims will address several of the most significant gaps in our understanding of the quasi-enveloped virus life cycle and pathogenesis.

 描述（申请人提供）：甲型肝炎病毒（HAV）和戊型肝炎病毒（HEV）感染是世界欠发达地区流行性食源性和水源性肝炎的常见原因。人畜共患病和血源性 HEV 传播及其在免疫抑制个体中持续存在的能力也令人震惊。美国人群的 HEV 血清反应呈阳性，这表明 HEV 暴露比以前认为的更为常见，尽管 HAV 和 HEV 都被认为是无包膜病毒，但最近的研究表明，HAV 和 HEV 在血液中以“准包膜”颗粒的形式出现。与经典的包膜病毒不同，其膜表面不存在病毒抗原，因此对中和抗体具有高度抵抗力。这种“准包膜”对肝炎病毒生命周期的影响，该提案将探讨准包膜 HAV 和 HEV 进入细胞并被抗体中和的机制，目的 1 将检验“准包膜”HAV 和 HEV 进入细胞的假设。细胞外囊泡摄取的细胞机制将确定准包膜 HAV 和 HEV 的中和机制。这些目标的完成将解决我们的几个最重要的差距。了解准包膜病毒的生命周期和发病机制。