GENE REGULATION OF MAMMALIAN DNA VIRUSES

我们计划对一系列家兔"白色痘"宿主范围突变体进行详细研究 痘病毒（RPmu突变体）在非允许细胞中在许多阶段被阻断 病毒的发展。 作为一项重大努力，我们计划继续绘制 对这些突变体的研究，我们已经证明是缺失的结果， 使用限制性内切酶分析。 我们对五个变种人的研究 已经检测到17%的病毒基因组在宿主范围内 显线体 我们的数据显示，这五种突变导致三种不同的 非允许细胞中的表型，提供了相关的可能性， 基因组的特定区域与特定功能相关联。 作为其中的一步， 方向，我们计划映射剩余的15个主机范围RPmu突变体在我们的 收集和描述它们，以确定合成中的哪些步骤， 大分子的加工在非允许宿主中被阻断以及原因。 我们 我还计划扩大我们的基因图谱研究，包括一系列"白色" pock "非宿主范围突变体，也可能是缺失，因为它们很容易 与宿主范围突变体重组，应该位于基因组的其他地方。 我们 已经从生物化学上鉴定了两种突变体， 在翻译的层面。 我们建议研究这一机制 translation block详细介绍 三个额外的突变体被阻止在水平 形态发生，和合成的异常病毒样颗粒不同， 彼此 我们计划通过生物物理和 电子显微镜手段，以及通过测定病毒体相关的酶 活动 由于宿主范围突变体的存在反映了生物化学 细胞之间的差异，我们希望利用我们的信息开始探索 这些差异允许选择性侵入靶器官， 并导致与给定病毒相关的疾病状态 感染

We plan to study in detail a series of "white pock" host range mutants of rabbit poxvirus (RPmu mutants) which in nonpermissive cells are blocked at many stages of viral development. As a major effort, we plan to continue our mapping studies on these mutants, which we have shown to be the result of deletions, by the use of restriction enzyme analysis. Our studies on the five mutants that we have examined have already implicated 17% of the viral genome in the host range phenonema. Our data show that these five mutants result in three different phenotypes in nonpermissive cells, offering the possiblity of correlating defined regions of the genome to a specific function. As a step in this direction, we plan to map the remaining 15 host range RPmu mutants in our collection and characterize them as to what steps in the synthesis and processing of macromolecules are blocked in the nonpermissive host and why. We also plan to extend our genetic mapping studies to include a series of "white pock" nonhost range mutants, also probably deletions, which because they readily recombine with the host range mutants, should lie elsewhere on the genome. We have already biochemically characterized two mutants which appear to be blocked at the level of translation. We propose to study the mechanism of this translation block in detail. Three additional mutants are blocked at the level of morphogenesis, and synthesized aberrant virus-like particles different from one another. We plan to characterize the aberrant particles by biophysical and electron microsopic means, as well as by assay of virion-associated enzymatic activities. Since the existence of host range mutants reflects biochemical differances between cells, we hope to use our information to begin to explore these differences which allow the selective invasion of target organs and tissues in vivo and lead to the disease state asociated with a given viral infection.