Ocular HSV-1:construction and analysis of AL mutants

眼部HSV-1：AL突变体的构建和分析

• 批准号: 6927819
• 负责人: DAVID J BRICK
• 金额: $ 5.15万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-08-01 至 2006-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6927819
• 关键词: antisense nucleic acid; blindness; functional /structural genomics; gene targeting; genetically modified animals; herpes simplex virus 1; laboratory rabbit; latent virus infection; ocular herpes; phenotype; postdoctoral investigator; protein structure function; tear; tissue /cell culture; transcription factor; virulence; virus genetics; virus infection mechanism

DESCRIPTION (provided by applicant): Recurrent HSV-I, due to reactivation of latent virus from sensory neurons, is a major cause of corneal blindness. LAT, the only viral transcript thought to be made during latency, is essential for efficient reactivation. Recently, a new viral transcript, AL, was found during latency. AL is anti-sense to LAT and produces a protein in infected rabbits. Since AL and LAT overlap, phenotypes previously attributed to LAT may be due to AL. Two hypotheses will be tested: AL plays a role in (1) spontaneous reactivation; and (2) virulence. My specific aim is to determine the function of AL. AL-/LAT + and AL+/LAT - mutants will be constructed and their reactivation and virulence phenotypes analyzed in the rabbit ocular model. These complementary mutants should allow us to determine if AL is involved in spontaneous reactivation and/or virulence, or if both phenotypes are due solely to LAT. This information will be critical to the development of novel strategies to reduce recurrent viral reactivation and conseequently reduce HSV-1 induced eye disease.

描述(由申请人提供)：由于感觉神经元潜伏病毒的重新激活，复发的单纯疱疹病毒I型是导致角膜失明的主要原因。Lat是被认为是在潜伏期内产生的唯一病毒转录本，对于有效的重新激活是必不可少的。最近，在潜伏期内发现了一种新的病毒转录本AL。AL对LAT是反义的，在感染的兔子中产生一种蛋白质。由于AL和LAT重叠，以前归因于LAT的表型可能是由于AL。将检验两个假设：AL在(1)自发再激活中起作用；(2)毒力。我的具体目的是确定AL的功能。将构建Al-/LAT+和AL+/LAT-突变体，并在兔眼模型中分析它们的再激活和毒力表型。这些互补的突变应该允许我们确定AL是否参与自发的再激活和/或毒力，或者是否两种表型都完全是由于LAT。这些信息将对开发新的策略来减少复发的病毒重新激活和持续减少HSV-1诱导的眼病至关重要。