Combinatory Genomic Assembly to Assess HSV-1 Phenotypes

疱疹病毒是所有DNA病毒中最大、最复杂和最可变的病毒之一。有一些 提供了有关病毒生物学的宝贵信息的常见实验室毒株。然而， 实验室菌株和临床分离株之间，甚至在不同的 临床分离株本身。很难理解这些差异是如何在 毒力和致病性。在这项应用中，合成生物学方法将首先用于构建 感染性克隆单纯疱疹病毒1型(HSV-1)基因组并展示其实用性和多功能性 这种基因组工程方法通过在临床分离株和实验室菌株之间创建嵌合体来 更容易确定临床菌株差异的功能后果。成功的结局 这种合成生物学方法的应用将对合成克隆和 操纵任何疱疹病毒基因组或大型病毒。这反过来将使更大的研究社区能够 更好地了解病毒的生物学。此外，这种方法还提供了一个范例来帮助理解 新兴病毒的生物学。

Herpesviruses are amongst the largest, most complex and most variable of all DNA viruses. There are some common laboratory strains which have provided valuable information on the biology of the viruses. However, there are behavioral differences between laboratory strains and clinical isolates and even within the different clinical isolates themselves. It has been difficult to understand how these differences are manifested in virulence and pathogenicity. In this application, synthetic biology methods will be used to first build an infectious clone of the herpes simplex virus type 1 (HSV-1) genome and then show the utility and versatility of this genome engineering method by creating chimeras between a clinical isolate and a laboratory strain to more easily determine the functional consequences of the clinical strain differences. The successful outcome of this synthetic biology approach would have a significant impact on the ability to synthetically clone and manipulate any herpesvirus genome or large virus. This, in turn, will enable the larger research community to better understand the biology of viruses. In addition, this approach offers a paradigm to help understand the biology of emerging viruses.