Comprehensive analyses of endogenous retroviruses with severe chronic fatigue syndrome

内源性逆转录病毒与严重慢性疲劳综合征的综合分析

基本信息

批准号：
9809684
负责人：
Dawei Li
金额：
$ 7.8万
依托单位：
UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-07-01 至 2021-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9809684
关键词：
Adoption Algorithms American Anti-inflammatory Antiviral Agents Area Autoantigens Bioinformatics Blood Tests Categories Chimeric Proteins Chronic Chronic Fatigue Syndrome Climacteric Clinical Complex DNA DNA Methylation Data Disease Double-Stranded RNA Endogenous Retroviruses Exertion FDA approved Fatigue General Population Genes Genetic Predisposition to Disease Genome Genotype Grant Human Genome Immune response Impaired cognition Individual Infectious Agent Inflammation Interferon Type I Lead Life Style Linear Regressions Location Malaise Maps Measurement Measures Medical Methylation Modeling Nutrient Outcome Pain Pathway interactions Patients Phenotype Pilot Projects Prevention Quality of life Research Retrovirus Proteins Risk Risk Factors Role Sampling Severities Sleep Disorders Testing Variant Work bacteriome case control cost cytokine deep sequencing demethylation design diagnostic biomarker exome frontier genome sequencing genome-wide genome-wide analysis methylome microbiome molecular marker novel novel therapeutic intervention tool transcriptome transcriptome sequencing viral RNA virome whole genome working group

项目摘要

Project Summary/Abstract Myalgic encephalomyelitis/chronic fatigue syndrome (referred to as CFS) is a debilitating disease characterized by unrelenting fatigue, post-exertional malaise, cognitive impairment, sleep problems, and pain. CFS disables 1-2.5 million Americans, and costs $17–24 billion annually. Clinical tests of CFS patients are typically normal. There are currently no molecular biomarkers or FDA-approved treatments. The cause of CFS is unknown. Recent data from ourselves and others show that CFS is a complex and misunderstood disease. This proposal is aimed at helping to understand the role of endogenous retrovirus (ERV) variations in the genetic predisposition for CFS. We propose a novel CFS model: polymorphic ERV insertions can be activated through demethylation, infectious agents, or both, and the resembled viral RNA triggers the inflammation pathway, ultimately leading to CFS. The co-contribution of genome-wide ERV variations and their activators is an unexplored research frontier and an important area for research in CFS. Here, we will focus on analyzing existing CFS genome, methylome, transcriptome, and microbiome data to identify ERV variations associated with CFS. Verifying ERV as a risk factor in CFS will aid in adoption of an antiviral or anti-inflammatory treatment or anti-inflammatory lifestyle. If ERV activators, such as demethylation or infectious agent triggers, are also found, research on this will eventually lead to new therapeutic intervention and prevention.

项目摘要/摘要肌力性脑脊髓炎/慢性疲劳综合征（称为CFS）是一种使人衰弱的疾病其特征是疲劳，锻炼后不适，认知障碍，睡眠问题和疼痛的特征。 CFS禁用1-250万美国人，每年的费用为17-24亿美元。 CFS患者的临床测试是通常正常。目前没有分子生物标志物或FDA批准的治疗方法。 CFS的原因是未知的。来自我们自己和其他人的最新数据表明，CFS是一种复杂且未被遗忘的疾病。该建议旨在帮助了解内源性逆转录病毒（ERV）变化在 CFS的遗传倾向。我们提出了一种新型CFS模型：可以激活多态性ERV插入通过脱甲基化，传染剂或两者兼而有之，并且类似的病毒RNA触发注射途径，最终导致CFS。全基因组ERV变异及其激活剂的共同贡献是意外的研究前沿和CFS研究的重要领域。在这里，我们将专注于分析现有的CFS基因组，甲基组，转录组和微生物组数据，以识别相关的ERV变化与CFS。将ERV验证为CFS的危险因素将有助于采用抗病毒或抗炎治疗或抗炎生活方式。如果ERV激活剂（例如脱甲基化或感染剂触发），还发现，对此的研究最终将导致新的治疗干预和预防。