Identifying Poxvirus Receptors

痘病毒是能够感染人类并引起人类疾病的DNA病毒的大家族。它的成员包括天花，天花的病原体，猴痘，导致天花样疾病，可致命。除了这些公共卫生问题之外，痘病毒正在被开发并用作疫苗平台和溶瘤剂。典型的痘病毒，牛痘，能够结合并进入每一种测试的细胞类型。目前，还没有确定痘病毒的明确的细胞受体，这是我们对其生命周期知识的一个主要空白。该项目的长期目标是确定哪些细胞受体能够与痘病毒病毒粒子表面上发现的约30种病毒蛋白中的哪一种相互作用，以便实现假型化和细胞靶向。我们的研究也将有助于理解牛痘病毒和该组其他成员所表现出的巨大向性。目前的目标是开发一个系统来筛选与牛痘病毒相互作用的细胞蛋白。然后，这些结果将扩展到该家族的其他成员（肢脱病病毒和粘液瘤病毒），以确定它们是否利用相同的受体，或者它们是否已经进化到使用不同的受体。我们的具体目标是：1）使用酵母表面展示筛选cDNA文库中的细胞内成熟形式的牛痘病毒可以结合的细胞蛋白。2)对牛痘病毒进行优先级排序和验证。确定缺肢症和粘液瘤是否可以结合筛选中鉴定的推定受体。所获得的结果将鉴定痘病毒使用的细胞受体，并为这些病毒的广泛嗜性的分子机制提供更深入的了解，沿着建立用于具有广泛嗜性的病毒的新受体筛选模式。

Poxviruses are a large family of DNA viruses capable of infecting and causing disease in humans. Its members include variola, the causative agent of smallpox, and monkeypox, which causes a smallpox-like disease that can be lethal. In addition to these public health issues, poxviruses are being developed and used as vaccine platforms and oncolytic agents. The prototypical poxvirus, vaccinia, is able to bind and enter, every cell type tested. Currently, an unambiguous cellular receptor has not been identified for poxviruses and represents a major gap in our knowledge of their lifecycle. The long-term goal of this project is to determine which cellular receptor(s) are capable of interacting with which of the ~30 viral proteins found on the surface of poxvirus virions so that pseudotyping and cell targeting can be achieved. Our studies will also help in understanding the vast tropism exhibited by vaccinia virus and other members of this group. The immediate goal is to develop a system to screen for cellular proteins that interact with vaccinia virus. These results will then be expanded to other members of this family (ectromelia virus and myxoma virus) to determine if they utilize the same receptors or if they have evolved to use different receptors. Our specific aims are; 1) Screen a cDNA library using yeast surface display for cellular proteins that the intracellular mature form of vaccinia virus can bind. 2) Prioritize and validate hits for vaccinia virus. Determine if ectromelia, and myxoma can bind putative receptors identified in the screen. The results obtained will identify cellular receptor(s) used by poxviruses and provide greater insight into the molecular mechanism of the broad tropism of these viruses, along with establishing a new receptor screening modality for viruses that have a broad tropism.