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。有一些 实验室常见病毒株，提供了有关病毒生物学的宝贵信息。然而，在这方面， 实验室菌株和临床分离株之间存在行为差异， 临床隔离。很难理解这些差异是如何表现在 毒力和致病性。在本申请中，合成生物学方法将用于首先构建一个 单纯疱疹病毒1型（HSV-1）基因组的感染性克隆，然后显示的实用性和多功能性， 该基因组工程方法通过在临床分离株和实验室菌株之间产生嵌合体， 更容易确定临床菌株差异的功能后果。取得圆满成果 这种合成生物学方法的发展将对合成克隆的能力产生重大影响， 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，这种方法提供了一个范例，以帮助理解 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.