Bioreagents Core

鼠痘(老鼠的天花)的病原体--蜕皮病病毒(ECTV)是为数不多的 可获得的天然老鼠病原体模型，它通过外周感染并通过 淋巴系统变得全身性并导致疾病。缺乏这种天然特性的实验系统 配对将错过很长一段时间共同进化形成的复杂的相互作用。这个 这个项目的三个项目的目标是剖析控制自然ECTV的机制 感染。该计划中的三个项目将需要基因操纵的ECTV。此外， CORE的试点研究项目将需要删除两个ECTV基因。痘病毒的基因组可以是 通过同源重组来消除基因或添加外源序列 对于有经验的人来说，涉及的程序相对简单。虽然大多数技术适用于 痘病毒的基因操作是针对牛痘病毒(VACV)而开发的，我们已经成功地应用于 同源重组以操纵蜕皮病病毒(ECTV)基因组。此外，项目2将 需要通过基因重组工程创造转基因小鼠，并创造袋子记者。委员会成员 CORE对这两种程序都有丰富的经验。核心的试点项目将是研究是否 ECTV免疫反应修饰物(IRM)EVM043和EVM145在毒力中起作用。这些基因是 已知会干扰宿主的1型干扰素反应。因此，这项研究将是补充 在项目2中进行了实验，并与该方案的总体目标完全一致。

Ectromelia virus (ECTV), the causative agent of mousepox (the smallpox of the mouse), is one of the few models available of a natural mouse pathogen that infects through the periphery and spreads through the lymphatic system to become systemic and cause disease. Experimental systems that lack this natural pairing will miss much of the complex interplay that has developed over a long period of co-evolution. The goal of the three programs in this project are to dissect the mechanisms that control a natural ECTV infection. The three projects in the Program will require genetically manipulated ECTV. In addition, the Core's pilot research project will require the deletion of two ECTV genes. The genomes of poxviruses can be manipulated by homologous recombination to either eliminate genes or to add foreign sequences and the procedures involved are relatively simple for experienced hands. While most of the techniques for the genetic manipulation of poxviruses were developed for vaccinia virus (VACV), we have successfully used homologous recombination to manipulate the ectromelia virus (ECTV) genome. In addition, Project 2 will need to create transgenic mice via genetic recombineering and to create BAG reporters. Members of the core have ample experience with both procedures. The Core's pilot project will be to study whether the ECTV immune response modifiers (IRMs) EVM043 and EVM145 play a role in virulence. These genes are known to interfere with the host Type 1 interferon response. Therefore, the research will complement experiments in Project 2 and is fully consistent with the overall goals of the Program.