IMMUNOPATHIC MYOSITIS INDUCED BY PERSISTENT VIRUS
持续病毒引起的免疫病性肌炎
基本信息
- 批准号:2072372
- 负责人:
- 金额:$ 19.18万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1993
- 资助国家:美国
- 起止时间:1993-09-30 至 1997-06-30
- 项目状态:已结题
- 来源:
- 关键词:Coxsackievirus RNase protection assay artificial immunosuppression athymic mouse autoimmune disorder computer assisted sequence analysis denervation disease /disorder model genetic regulation genetic strain host organism interaction laboratory mouse latent virus infection molecular cloning myositis natural selections tissue /cell culture virus RNA virus diseases
项目摘要
Enterovirus infection has been linked to the expression of several human
autoimmune diseases including polymyositis, juvenile-onset diabetes, and
cardiomyopathy. Evidence of prior enterovirus infection includes elevated
antibody titers against virus and the detection of persistent viral RNA in
the afflicted tissue. However, results from some studies are equivocal,
and hence the role of enterovirus in precipitating autoimmune diseases is
still unclear. Techniques for the detection of persistent enteroviruses
are hampered by a lack of knowledge about the mechanism which underlies
persistence. Similarly, the mariner in which persistent enterovirus
provokes the induction or maintenance of immunologically-mediated tissue
damage is not understood. This proposal employs a mouse model of
coxsackievirus B 1-induced polymyositis to study mechanisms of virus
persistence and evaluate the effect of virus persistence on immunopathic
muscle disease. Two key attributes of this model are that viral RNA
persists for long periods of time in muscle, and immunopathic disease is
mediated by T cells. The first objective is to explore the nature of
persistent virus and determine whether it is comprised of altered forms of
viral RNA and/or infectious virus. Nuclease protection assays will be used
to identify genomic deletions, sequence changes, and altered ratios of
positive and negative RNA strands. Reactivation of infectious virus will
be attempted with several different strategies including immunosuppression
and muscle denervation. A somewhat unique strategy for virus reactivation
will be to culture muscle in vitro where it is removed from potential
anti-viral effects of the immune system. Tissues other than muscle that
have previously been found to harbor persistent viral RNA will also be
tested as potential reservoirs of virus. If infectious virus is recovered,
it will be phenotypically and genotypically characterized and compared
with the original infecting strain. The second objective seeks to better
understand factors that influence the coevolution of host and virus, and
focuses on selective pressures exerted by the host on development of virus
persistence. Nude mice and inbred strains of mice with varying
susceptibilities to myositis will be used to examine the influence of T
cells and host background genes on the establishment of persistent
infection. The third objective is to identify muscle genes that are
differentially regulated as a result of virus persistence. The
differential display technique will be used to analyze muscle for RNA
transcripts that are upregulated or downregulated at different stages of
the disease. Taken together, these experiments will clarify important
interactions between persistent virus and the host that culminate in the
development of immunopathic muscle disease. They will also lead to more
effective approaches for the epidemiologic study of persistent virus-
induced autoimmune disease.
肠道病毒感染与几种人类
自身免疫性疾病,包括多发性肌炎、青少年发病的糖尿病,以及
心肌病既往肠道病毒感染的证据包括
抗病毒抗体滴度和持续病毒RNA的检测
受损组织然而,一些研究的结果是模棱两可的,
因此肠道病毒在诱发自身免疫性疾病中的作用是
目前仍不清楚.持久性肠道病毒的检测技术
由于缺乏对这一机制的了解,
坚持不懈同样,在水手中,
引起免疫介导组织的诱导或维持
伤害不被理解。该提议采用了小鼠模型,
柯萨奇病毒B 1诱导的多发性肌炎研究病毒机制
持久性和评估病毒持久性对免疫性疾病的影响
肌肉疾病该模型的两个关键属性是,
在肌肉中持续很长一段时间,免疫性疾病是
由T细胞介导。第一个目标是探讨
持续存在的病毒,并确定它是否由改变形式的
病毒RNA和/或感染性病毒。将使用核酸酶保护试验
以确定基因组缺失、序列变化和
正和负RNA链。感染性病毒的重新激活将
可以尝试几种不同的策略,包括免疫抑制
和肌肉去神经。一种独特的病毒再激活策略
将在体外培养肌肉,
免疫系统的抗病毒作用。肌肉以外的组织,
此前被发现携带持久性病毒RNA的人也将被发现
被检测为潜在的病毒宿主如果发现感染性病毒,
它将被表型和基因型表征和比较,
与最初的感染菌株第二个目标是更好地
了解影响宿主和病毒共同进化的因素,
着重于宿主对病毒发展施加的选择性压力
坚持不懈裸鼠和近交系小鼠具有不同的
对肌炎的易感性将被用来检查T
细胞和宿主背景基因对建立持久性
感染第三个目标是确定肌肉基因,
由于病毒持续存在而受到不同的调节。的
差异显示技术将用于分析肌肉的RNA
转录本在不同阶段上调或下调,
这种疾病综合起来,这些实验将阐明重要的
持续存在的病毒和宿主之间的相互作用,
免疫性肌肉疾病的发展。它们也将导致更多的
持续性病毒流行病学研究的有效方法-
诱发自身免疫性疾病
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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RONALD P MESSNER其他文献
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{{ truncateString('RONALD P MESSNER', 18)}}的其他基金
TOLEROGENIC STEM CELL TRANSPLANTATION FOR ARTHRITIS
关节炎耐受性干细胞移植
- 批准号:
6171857 - 财政年份:1999
- 资助金额:
$ 19.18万 - 项目类别:
TOLEROGENIC STEM CELL TRANSPLANTATION FOR ARTHRITIS
关节炎耐受性干细胞移植
- 批准号:
6375121 - 财政年份:1999
- 资助金额:
$ 19.18万 - 项目类别:
TOLEROGENIC STEM CELL TRANSPLANTATION FOR ARTHRITIS
关节炎耐受性干细胞移植
- 批准号:
6511923 - 财政年份:1999
- 资助金额:
$ 19.18万 - 项目类别:
TOLEROGENIC STEM CELL TRANSPLANTATION FOR ARTHRITIS
关节炎耐受性干细胞移植
- 批准号:
2909823 - 财政年份:1999
- 资助金额:
$ 19.18万 - 项目类别:
IMMUNOPATHIC MYOSITIS INDUCED BY PERSISTENT VIRUS
持续病毒引起的免疫病性肌炎
- 批准号:
2901587 - 财政年份:1993
- 资助金额:
$ 19.18万 - 项目类别:
IMMUNOPATHIC MYOSITIS INDUCED BY PERSISTENT VIRUS
持续病毒引起的免疫病性肌炎
- 批准号:
6169785 - 财政年份:1993
- 资助金额:
$ 19.18万 - 项目类别:
IMMUNOPATHIC MYOSITIS INDUCED BY PERSISTENT VIRUS
持续病毒引起的免疫病性肌炎
- 批准号:
2072371 - 财政年份:1993
- 资助金额:
$ 19.18万 - 项目类别:
IMMUNOPATHIC MYOSITIS INDUCED BY PERSISTENT VIRUS
持续病毒引起的免疫病性肌炎
- 批准号:
6532703 - 财政年份:1993
- 资助金额:
$ 19.18万 - 项目类别:
IMMUNOPATHIC MYOSITIS INDUCED BY PERSISTENT VIRUS
持续病毒引起的免疫病性肌炎
- 批准号:
3150373 - 财政年份:1993
- 资助金额:
$ 19.18万 - 项目类别:
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