The Relationship of XMRV to Functional Status and Co-infections in Chronic Fatigu

XMRV 与慢性疲劳功能状态和合并感染的关系

• 批准号: 7977530
• 负责人: MAUREEN REBECCA HANSON
• 金额: $ 26.95万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-06-15 至 2012-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7977530
• 关键词: Aerobic Exercise; American; Amino Acid Substitution; Anaerobic Threshold; Antibodies; Arthralgia; Autonomic nervous system; Bacteria; Bacterial Infections; Blood; Blood Cell Count; Blood Cells; Cells; Child; Childhood; Chronic; Chronic Fatigue Syndrome; DNA Microarray Chip; Development; Disease Outbreaks; Etiology; Exercise; Exercise stress test; Exhibits; Fatigue; Functional disorder; Gammaretrovirus; Genes; Growth Factor; Headache; Health; Health Status; Human; Human Herpesvirus 6; Immune; Immune System and Related Disorders; Immune system; Individual; Infection; Inflammatory; Learning; Location; Malaise; Measurement; Measures; Memory; Methods; Microbe; Monitor; Morphology; Murine leukemia virus; Myalgia; Names; Nevada; New York; Nitric Oxide; Nucleic Acids; Oxygen Consumption; Parasites; Patients; Performance; Phylogenetic Analysis; Physical activity; Physiological; Play; Production; Proviruses; Reporting; Retroviridae; Role; Rural; Sampling; Sleep; Sore Throat; Symptoms; Testing; Variant; Vascular Endothelial Growth Factors; Viral; Viral Proteins; Virus; Virus Diseases; cohort; cytokine; design; disability; experience; functional status; loss of function; lymph nodes; member; pathogen; patient population; prevent; protein expression; public health relevance; research study; virus envelope

DESCRIPTION (provided by applicant): Chronic fatigue syndrome (CFS) is an illness characterized by long-term fatigue, impaired memory or concentration, sore throat, tender lymph nodes, muscle pain, multi-joint pain, new headaches, unrefreshing sleep, and exercise intolerance. While the cause(s) of chronic fatigue syndrome has not been established definitively, a number of outbreaks implicate an infectious etiology. A variety of pathogens have been reported in individual CFS patients or found more frequently in CFS patients than controls, including various types of viruses. The immune systems of CFS patients exhibit both chronic activation and dysfunction. Recently, a new human retrovirus named XMRV (Xenotropic Murine Leukemia Virus-Related Virus) has been detected in a large proportion of CFS patients tested, but in only 4% of healthy subjects. We plan to learn more about the association of XMRV and other pathogens with CFS by examining an outbreak cohort not previously screened for the presence of XMRV. Other viruses, microbes, and parasites that may be associated with XMRV will also be detected with the use of a panmicrobial DNA microarray. We will determine whether the presence of XMRV and/or other pathogens is related to the current state of health of individuals who became ill during a 1985 outbreak in rural New York. Assuming that most members of the New York cohort are infected with XMRV, we will amplify and sequence XMRV envelope genes derived from blood cells of 40 individuals who became ill as children in 1985. We will also sequence envelope genes from 80 subjects in the Nevada cohort known to exhibit a high degree of XMRV infection. We will examine phylogenetic relationships between the Nevada and New York XMRV variants and will observe whether any amino acid substitutions correlate with the current state of health of the subjects. We will also study the possible association of XMRV and XMRV protein expression in the phenomenon of exercise intolerance. We will examine XMRV-infected CFS patients before and after an exacerbation of symptoms caused by serial exercise testing. We will determine whether increases in inflammatory cytokines, a growth factor, and nitric oxide, or blood cell changes are correlated with the extent of reduced physical ability that can be measured during a second exercise test taken after induction of postexertional malaise. All of these experiments will be designed to assess whether particular XMRV sequences and expression levels play a role in the symptoms experienced by CFS patients and to detect possible underlying mechanisms of the disability that impairs their physical activity. PUBLIC HEALTH RELEVANCE: Chronic fatigue syndrome, an illness that disables many Americans, has recently been associated with the presence of a new human retrovirus. We will investigate whether this retrovirus is both necessary and sufficient for the development of the illness, or whether additional pathogens are involved. We will determine whether the level of health and exercise intolerance in chronic fatigue syndrome is related to particular virus variants, expression of viral proteins, and/or dysfunction of the immune system.

描述（由申请人提供）：慢性疲劳综合征（CFS）是一种以长期疲劳、记忆或注意力受损、喉咙痛、淋巴结痛、肌肉痛、多关节痛、新发头痛、睡眠不清和运动不耐受为特征的疾病。虽然慢性疲劳综合征的病因尚未明确确定，但一些疾病的爆发与感染性病因有关。据报道，在个别CFS患者中存在多种病原体，或在CFS患者中发现的病原体比对照组更频繁，包括各种类型的病毒。慢性疲劳综合症患者的免疫系统表现为慢性激活和功能障碍。最近，一种名为XMRV（异嗜性小鼠白血病病毒相关病毒）的新型人类逆转录病毒已在大部分CFS患者中检测到，但在健康受试者中仅占4%。我们计划通过检查一个以前没有筛选过XMRV存在的爆发队列，更多地了解XMRV和其他病原体与CFS的关系。其他可能与XMRV相关的病毒、微生物和寄生虫也将使用泛微生物DNA微阵列进行检测。我们将确定XMRV和/或其他病原体的存在是否与1985年在纽约农村暴发期间患病的个人目前的健康状况有关。假设纽约队列的大多数成员都感染了XMRV，我们将扩增并测序从1985年儿童时期患病的40个人的血细胞中提取的XMRV包膜基因。我们还将对内华达州队列中已知表现出高度XMRV感染的80名受试者的包膜基因进行测序。我们将检查内华达和纽约XMRV变体之间的系统发育关系，并观察是否有任何氨基酸替换与受试者当前的健康状况相关。我们还将研究XMRV和XMRV蛋白表达在运动不耐受现象中的可能关联。我们将检查xmrv感染的CFS患者在一系列运动试验引起的症状加重之前和之后。我们将确定炎症细胞因子（一种生长因子）和一氧化氮（一氧化氮）或血细胞变化的增加是否与体力下降的程度相关，这种程度可以在运动后不适诱导后进行第二次运动试验时测量。所有这些实验都旨在评估特定的XMRV序列和表达水平是否在CFS患者所经历的症状中发挥作用，并检测损害其身体活动的残疾可能的潜在机制。