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、记忆力或注意力受损、咽喉痛、淋巴结压痛、肌肉疼痛、多关节疼痛、新发头痛、睡眠不振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确定，但一些暴发涉及感染性病因。各种病原体已报告在个别CFS患者或发现更频繁的CFS患者比对照组，包括各种类型的病毒。CFS患者的免疫系统表现出慢性激活和功能障碍。最近，一种名为XMRV（异嗜性鼠白血病病毒相关病毒）的新人类逆转录病毒已在大部分CFS患者中检测到，但仅在4%的健康受试者中检测到。我们计划通过检查一个以前没有筛查过XMRV存在的暴发队列，了解更多关于XMRV和其他病原体与CFS的关联。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年纽约农村暴发期间患病的个人的当前健康状况有关。假设纽约队列的大多数成员感染了XMRV，我们将扩增和测序来自40个在1985年儿童时期患病的个体的血细胞的XMRV包膜基因。我们还将对已知表现出高度XMRV感染的内华达州队列中的80名受试者的包膜基因进行测序。我们将研究内华达州和纽约XMRV变异体之间的系统发育关系，并观察是否有任何氨基酸取代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患者之前和之后的一系列运动试验引起的症状加重。我们将确定是否增加炎症细胞因子，生长因子，一氧化氮，或血细胞的变化与体力下降的程度，可以测量在第二次运动试验后，诱导运动后不适。所有这些实验将被设计为评估特定的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的可能潜在机制。 公共卫生相关性：慢性疲劳综合症，一种使许多美国人致残的疾病，最近与一种新的人类逆转录病毒的存在有关。我们将研究这种逆转录病毒是否是疾病发展的必要和充分条件，或者是否涉及其他病原体。我们将确定慢性疲劳综合征的健康水平和运动不耐受是否与特定的病毒变体，病毒蛋白的表达和/或免疫系统功能障碍有关。