THE MOLECULAR BIOLOGY OF REPLICATION RNA TUMOR VIRUSES

复制RNA肿瘤病毒的分子生物学

基本信息

批准号：
3165141
负责人：
WILLIAM A. HASELTINE
金额：
$ 10.77万
依托单位：
DANA-FARBER CANCER INST
依托单位国家：
美国
项目类别：
财政年份：
1979
资助国家：
美国
起止时间：
1979-06-01 至 1988-08-31
项目状态：
已结题

项目摘要

The goal of these studies is to elucidate the role specific sequences of the LTR of murine retroviruses as determinants of tissue secificity of infection and of pathogenicity. The objectives are: 1. To test the generality of the hypothesis that enhancer sequences in the LTR determine the tissue tropism and pathogenicity of murine retroviruses. Specific aims of this objective are to construct isogenic LTRs that differ only in the enhancer region. Enhancer elements of thymotropic, erythrotropic and B cell tropic viruses will be exchanged. 2. To determine whether cellular as well as viral enhancer elements incorporated into viral LTR sequences can function as enhancers for virus replication and can confer tissue specificity upon viral replication. The specific aims include construction of hybrid LTR sequences that contain cellular enhancer sequences. 3. To define the sequences within the U3 region of the LTR of murine viruses that determine tissue specific transcriptional preference. Specific aims include alterations in the sequence and sequence arrangement within the tandemly duplicated sequences of the U3 portion of the LTR. 4. To determine whether or not tissue specific enhancer functions are dominant, co-dominant, or recessive. Specific hybrid constructions that contain two or more enhancer sequences derived from different viruses will be constructed. These experiments should provide input in viral pathogenesis. They should also yield information important for understanding of gene expression in differentiated tissues.

这些研究的目的是阐明角色的特定序列鼠逆转录病毒的LTR作为组织确定性的决定因素感染和致病性。目标是： 1。测试假设的一般性，即增强子序列 LTR确定了鼠逆转录病毒的组织往流和致病性。该目标的具体目的是构建不同的ISEGENIC LTR 仅在增强剂区域。促脑质的增强子元素，将交换红细胞和B细胞热带病毒。 2。确定细胞和病毒增强子元素是否掺入病毒LTR序列中可以充当病毒的增强子复制并可以在病毒复制后赋予组织特异性。这具体目的包括构建包含的混合LTR序列细胞增强子序列。 3。定义鼠LTR的U3区域内的序列确定组织特异性转录偏好的病毒。具体目的包括序列和序列布置的改变在LTR的U3部分的串联重复序列中。 4。确定组织特定增强子功能是否是占主导地位，主导或隐性。特定的混合构造包含从不同病毒得出的两个或多个增强子序列被构造。这些实验应提供病毒发病机理的输入。他们应该也产生有关理解基因表达重要的信息分化的组织。