Combinatory Genomic Assembly to Assess HSV-1 Phenotypes

用于评估 HSV-1 表型的组合基因组组装

• 批准号: 8779612
• 负责人: Sanjay Vashee
• 金额: $ 22.6万
• 依托单位: J. CRAIG VENTER INSTITUTE, INC.
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-12-10 至 2017-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8779612
• 关键词: Bacterial Genome; Basic Science; Behavioral; Biological; Biological Assay; Biology; Blindness; Cell Culture System; Chimera organism; Clinical; Cloning; Code; Collaborations; Communities; Complex; DNA; DNA Sequence; DNA Viruses; Elements; Encephalitis; Future; Genes; Genetic; Genome; Genome engineering; Genomic Segment; Genomic approach; Genomics; Goals; Herpesviridae; Herpesvirus 1; Human; Immune response; Investigation; Laboratories; Lead; Mammalian Cell; Mediating; Methodology; Methods; Microbe; Mutation; One-Step dentin bonding system; Outcome; Pathogenicity; Phenotype; Plasmids; Process; Property; Proteins; Recombinants; Research; Research Personnel; Simplexvirus; Technology; Testing; Time; Toll-Like Receptor 2; Virulence; Virus; Virus Diseases; Work; base; citizen science; genome sequencing; high risk; mutant; public health relevance; reconstitution; synthetic biology; tool; viral DNA

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.

疱疹病毒是所有DNA病毒中最大，最复杂和最可变的。有一些 普通实验室应变提供了有关病毒生物学的宝贵信息。然而， 实验室菌株和临床分离株乃至不同的行为差异 临床隔离。很难理解这些差异是如何表现出来的 毒力和致病性。在此应用中，合成生物学方法将首先构建 单纯疱疹病毒1型（HSV-1）基因组的传染性克隆，然后显示 这种基因组工程方法是通过在临床分离株和实验室压力之间创建嵌合体的 更容易确定临床应变差异的功能后果。成功的结果 这种合成生物学方法将对合成克隆和 操纵任何疱疹病毒基因组或大型病毒。反过来，这将使更大的研究社区能够 更好地了解病毒的生物学。此外，这种方法提供了一种范式来帮助了解 新兴病毒的生物学。