BASIS FOR THE IFP PHENOTYPE OF DIABETOGENIC EMC VIRUS
BASIS FOR THE IFP PHENOTYPE OF DIABETOGENIC EMC VIRUS
批准号:
3232586
负责人:
GEORGE W JORDAN
金额:
$15.24万
依托单位国家:
美国
项目类别:
财政年份:
1984
资助国家:
美国
项目状态:
已结题
起止时间:
1984-07-01 至 1991-06-30
关键词:
autoradiography complementary DNA encephalomyocarditis virus gel electrophoresis gene expression genetic manipulation genetic mapping genetic strain genetic translation insulin dependent diabetes mellitus interferons laboratory mouse molecular cloning nucleic acid chemical synthesis nucleic acid probes nucleic acid sequence pancreatic islet disorder plasmids tissue /cell culture transfection virus RNA virus genetics virus related diabetes mellitus
中文摘要
脑心肌炎(EMC)病毒诱导的糖尿病
小鼠与青少年糖尿病的一个亚群有相似之处
人类。两个在其他方面相似的变种源自M-
EMC病毒株可用于研究不同毒株
干扰素诱导颗粒(IFP)的表型及其能力
导致小鼠患糖尿病。EMC-B变种是IFP,可产生高
感染小鼠循环中的干扰素水平,原因
胰岛感染有限,不会导致糖尿病。
当循环中的干扰素被抗干扰素球蛋白中和时,
糖尿病是由感染EMC-B病毒引起的,这表明
干扰素系统,可能是IFP的表型,是决定因素
糖尿病的结局。EMC-D的变种是IFP-,产量较低
循环中的干扰素水平,破坏胰岛及其原因
小鼠的糖尿病。关键的遗传差异必须对
这些密切相关的病毒的不同生物学特性。
为了确定这些特性的遗传基础,我们
克隆了与完整开放阅读相对应的cDNAs
这两个变种的框架。它们的限制性内切酶图谱是
对于12种不同的酶来说是相同的。另外,前103个核苷酸
在基因组5‘端的未翻译的RNA中
一模一样。我们建议发现IFP的遗传基础
EMC病毒表型和糖尿病致病性的初步比较
B和D变异体的完整核苷酸序列。这个
核苷酸序列差异的功能意义
都出现在开放阅读框中,将被确定
通过参照RNA的体外翻译产物
转录本和EMC病毒蛋白的已知功能。
将合成B和D变异体的完整cDNA用于
哺乳动物细胞的转基因。关于差异
在开放阅读框之内或之外核苷酸序列中,
将合成B和D的嵌合分子。生物学的
重组病毒的性质将按顺序确定
以独立确定导致该疾病的遗传基因座
IFP的表型和糖尿病的发生。这一知识将进一步
我们对病毒毒力和病毒致病机制的认识
病毒诱导的干扰素。使用由此提供的数据
项目,有可能预测人类的毒力
病毒来源于对遗传结构的了解。
英文摘要
Encephalomyocarditis (EMC) virus induced diabetes mellitus in
mice has similarities to a subset of juvenile onset diabetes in
humans. Two otherwise similar variants derived from the M-
strain of EMC virus are available for study that differ in their
interferon inducing particle (ifp) phenotype and in their ability to
cause diabetes in mice. The EMC-B variant is ifp+, produces high
levels of circulating interferon (IFN) in infected mice, causes
limited infection of pancreatic islets, and does not cause diabetes.
When circulating IFN is neutralized by anti-IFN globulins,
diabetes results from infection with EMC-B indicating that the
interferon system, possibly the ifp phenotype, is a determinant of
the diabetic outcome. The EMC-D variant is ifp-, produces lower
levels of circulating IFN, destroys pancreatic islets and causes
diabetes in mice. Key genetic differences must be responsible for
the different biological properties of these closely related viruses.
In order to determine the genetic basis for these properties we
have cloned cDNA corresponding to the complete open reading
frame of both variants. Their restriction endonuclease maps are
identical for 12 different enzymes. Also, the first 103 nucleotides
of the untranslated RNA at the 5' end of the genomes are
identical. We propose to discover the genetic basis for the ifp
phenotype and diabetogenicity of EMC virus by first comparing
the complete nucleotide sequences of the B and D variants. The
functional significance of differences in nucleotide sequence that
are found to occur in the open reading frame will be ascertained
by reference to the in vitro translation products of RNA
transcripts and to the known functions of EMC viral proteins.
Complete cDNA of the B and D variants will be synthesized for
transfection of mammalian cells. With reference to differences
in nucleotide sequence within or outside the open reading frame,
chimeric molecules of B and D will be synthesized. The biological
properties of the recombinant viruses will be determined in order
to independently determine the genetic locus responsible for the
ifp phenotype and diabetogenicity. This knowledge will further
our understanding of virus virulence and the mechanism of
interferon induction by viruses. Using data provided by this
project, it may be possible to predict the virulence of human
viruses from a knowledge of genetic structure.
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BASIS FOR DIABETOGENICITY OF ENCEPHALOMYOCARDITIS VIRUS
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批准号:3153106
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项目类别:
-
资助金额:$12.32万
-
财政年份:1984
-
负责人:GEORGE W JORDAN
-
依托单位:
BASIS FOR DIABETOGENICITY OF ENCEPHALOMYOCARDITIS VIRUS
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批准号:3232585
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项目类别:
-
资助金额:$12.04万
-
财政年份:1984
-
负责人:GEORGE W JORDAN
-
依托单位:
BASIS FOR THE IFP PHENOTYPE OF DIABETOGENIC EMC VIRUS
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批准号:3232587
-
项目类别:
-
资助金额:$15.15万
-
财政年份:1984
-
负责人:GEORGE W JORDAN
-
依托单位:
BASIS FOR THE IFP PHENOTYPE OF DIABETOGENIC EMC VIRUS
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批准号:3232583
-
项目类别:
-
资助金额:$14.84万
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财政年份:1984
-
负责人:GEORGE W JORDAN
-
依托单位:
海外基金