RETROVIRUS EVOLUTION

描述：(改编自研究人员的摘要)：逆转录病毒显示 与东道主进行的各种不同的互动，远远超出了 任何其他病毒组。这种变化是由于 病毒的生命周期，包括复制期间的高突变率，独一无二 在每个复制周期整合其DNA的能力(和必要性，以及 基因组某些部分的特殊特征，包括包膜基因 和LTR，它们允许快速适应宿主细胞表现出的不同 表面受体和在不同转录程序中。对于许多人来说 多年来，我们的实验室一直在研究生物多样性的不同方面 逆转录病毒与宿主的进化相互作用。这些领域包括： 遗传变异的机制和作用--点突变、同源突变和 在体外遗传变异中的非法重组，LTR的方式 而env序列能够改变它们的表达模式和受体 用途；内源性前病毒的性质和演变。未来的研究将 继续沿着同样的路线前进。我们的目标是：研究突变和选择， 我们将继续发展我们的方法来量化非常 低频率；使用这些方法测试逆转录病毒进化的模型 (点突变和重组的积累)； 建立和扩展逆转录病毒变异和短期的数学模型 进化论。为了研究env基因的进化，我们将分析禽类逆转录病毒。 扩大寄主范围的体外选择分离的env基因变异体 将决定这些变异的进化路径；我们将 确定内源性“祖传”包膜基因的功能特性；以及 我们将测试从正常细胞进化出env基因的可能性。 基因。我们将通过继续研究内源性前病毒的进化 利用Se序列剖析内源MLV与野鼠的共同进化 用于测试灵长类进化模型的内源性人类前病毒 为什么大量的人类内源性前病毒没有引起 传染性病毒。

DESCRIPTION: (Adapted from the investigator's abstract): Retroviruses display a remarkable variety of interactions with their hosts, well beyond that known for any other virus group. This variety is a consequence of special features of the virus life cycle, including a high mutation rate during replication, the unique ability (and necessity to integrate their DNA at every replication cycle, and special features of certain parts of the genome, including the envelope gene and the LTR, that allow rapid adaptation to host cells displaying different surface receptors and in different transcription programs. For a number of years, our laboratory has been studying a number of different aspects of the evolutionary interaction of retroviruses with their host. These areas include: the mechanisms and role of genetic variation - point mutation, homologous and illegitimate recombination in genetic variation in vitro, the way in which LTR and env sequences are able to vary their patterns of expression and receptor usage; the nature and evolution of endogenous proviruses. Future studies will continue along the same lines. Our aims are: To study mutation and selection, we will continue development of our approach toward quantitation of very low-frequency; use these approaches to test models for retrovirus evolution (accumulation of point mutations and recombination) in simple culture; and develop and extend mathematical models for retrovirus variation and short-term evolution. To study evolution of env genes, we will analyze avian retrovirus env gene variants isolated by in vitro selection for extended host range; we will determine the evolutionary pathway by which such variants; we will determine the functional properties of "ancestral" env genes in endogenous; and we will test the possibility of evolution of env genes from normal cellular genes. We will study the evolution of endogenous proviruses by continuing to dissect the coevolution of endogenous MLV's and wild mice; using se sequences of endogenous human proviruses to test models of primate evolution; and testing why the large numbers of human endogenous proviruses do not give rise to infectious virus.