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

• 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
• 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

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.

项目总结/摘要 肌痛性脑脊髓炎/慢性疲劳综合征（简称CFS）是一种使人衰弱的疾病 其特征在于持续疲劳、运动后不适、认知障碍、睡眠问题和疼痛。 CFS使100万至250万美国人残疾，每年花费170亿至240亿美元。CFS患者的临床测试是 典型的正常。目前还没有分子生物标志物或FDA批准的治疗方法。CFS的原因 不明我们和其他人最近的数据表明，CFS是一种复杂和被误解的疾病。 该建议旨在帮助理解内源性逆转录病毒（ERV）变异在逆转录病毒感染中的作用。 CFS的遗传易感性我们提出了一个新的CFS模型：多态性ERV插入可以被激活 通过去甲基化，感染因子，或两者兼而有之，和类似的病毒RNA触发炎症 最终导致CFS。全基因组ERV变异及其激活剂的共同贡献是 一个未开发的研究前沿和CFS研究的重要领域。在这里，我们将重点分析 现有CFS基因组、甲基化组、转录组和微生物组数据，以确定ERV相关变异 关于CFS作为CFS的一个危险因素，MENERV将有助于采用抗病毒或抗炎药物。 治疗或抗炎的生活方式。如果ERV激活剂，如去甲基化或感染因子触发， 也发现，对这方面的研究将最终导致新的治疗干预和预防。