RETROVIRUS EVOLUTION

描述：（改编自研究者摘要）：逆转录病毒显示 它们与宿主之间的相互作用种类繁多， 其他病毒群。这种多样性是一个后果的特殊功能的 病毒的生命周期，包括复制过程中的高突变率，独特的 在每个复制周期中整合其DNA的能力（和必要性）， 基因组某些部分的特殊特征，包括包膜基因 和LTR，其允许快速适应显示不同 表面受体和不同的转录程序。由于多种 多年来，我们的实验室一直在研究一些不同的方面， 逆转录病毒与其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，同源和 体外遗传变异中的非法重组，LTR 和env序列能够改变它们的表达模式， 使用;内源性前病毒的性质和进化。未来的研究将 继续沿着同样的路线。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， 低频;使用这些方法来测试逆转录病毒进化的模型 （点突变和重组的积累）;和 开发和扩展逆转录病毒变异和短期 进化为了研究env基因的进化，我们将分析禽逆转录病毒 通过体外选择分离的env基因变异体，用于扩大宿主范围;我们 将决定这种变异的进化途径;我们将 确定内源性“祖先”env基因的功能特性;和 我们将测试env基因从正常细胞中进化的可能性， 基因.我们将继续研究内源性前病毒的进化， 剖析内源性MLV和野生小鼠的共同进化;使用se序列 内源性人类前病毒，以测试灵长类动物进化模型; 为什么大量的人类内源性前病毒不会引起 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.