Retrovirus Evolution

项目总结(见说明)： 逆转录病毒表现出丰富的进化现象，包括复制种群的能力 在不同的选择压力下经历快速的基因变化；在使用寄主时的能力 细胞受体；以及整合到寄主物种基因组中并传递给后代的能力 以内源性前病毒的形式代代相传。在之前的项目期间，我们已经聘请了所有这些 逆转录病毒进化方面：我们通过分析不寻常的突变来研究env基因的进化。 这将ALV的宿主范围从鸡扩展到鹌鹑、狗，甚至人类细胞。我们已经分析了 进化途径以及涉及的新的生化机制。我们有广泛的 分析了逆转录病毒及其宿主在人类和小鼠体内的共同进化。我们已经调查了 重要的抗病毒宿主因子AP0BEC3G在内源性MLV和MLV进化中的作用 外源性艾滋病毒。我们已经为复制病毒的进化建立了复杂的数学模型 种群，描述突变、选择、漂移、连锁和重组对 有害突变的积累(或丢失)，并开始开发应用体外模型系统 把这些模型带到现实世界。未来的工作将继续这些研究，目标如下。1.怎么做？ 逆转录病毒包膜基因从受体独立性进化到使用新的受体并改变其他受体 重要的特性？2.人类内源性的功能和致病特性是什么 逆转录病毒，特别是HERV-K？这些元素中是否有任何元素仍处于活动状态并能够复制 在人类基因组的新位置整合？3.重要的突变、选择、 重组和漂移结合起来引导逆转录病毒进化吗？

PROJECT SUMMARY (See instmctions): Retroviruses exhibit a wealth of evolutionary phenomena, including the ability of replicating populations to undergo rapid genetic change in response to varying selective pressure; the ability to vary in the use of host cell receptors; and the ability to become integrated in the genome of their host species and passed down through the generations as endogenous proviruses. In the prior project period, we have engaged all these aspects of retrovirus evolution: We have studied the evolution of env genes by analyzing unusual mutants that extend the host range of ALV beyond chicken, to quail, dog, and even human cells. We have analyzed the evolutionary pathway as well as the novel biochemical mechanism involved. We have extensively analyzed the coevolution of retroviruses and their hosts, both in humans and in mice. We have probed the role of an important antiviral host factor (AP0BEC3G) in the evolution of both endogenous MLV and exogenous HIV. We have developed sophisticated mathematical models for the evolution of replicating virus populations, describing the effects of mutation, selection, drift, linkage, and recombination on the accumulation (or loss) of deleterious mutations, and begun development of an in vitro model system to apply these models to the real world. Future work will continue these studies, with the following aims. 1. How do retroviral envelope genes evolve from receptor independence to use new receptors and to alter other important properties? 2. What are the functional and pathogenic properties of human endogenous retroviruses, particularly HERV-K? Are any of these elements still active and capable of replication and integration at new sites in the human genome? 3. How do important forces of mutation, selection, recombination, and drift combine to direct retrovirus evolution?