Ocular HSV-1:construction and analysis of AL mutants

描述（由申请人提供）：由于感觉神经元潜伏病毒的再激活，复发性单纯疱疹i型是角膜失明的主要原因。LAT是唯一被认为在潜伏期产生的病毒转录物，对有效的再激活至关重要。最近，在潜伏期发现了一种新的病毒转录本AL。AL对LAT具有反义作用，在感染家兔体内产生一种蛋白。由于AL和LAT重叠，以前归因于LAT的表型可能是由于AL。我们将测试两种假设：AL在(1)自发再激活中起作用；(2)毒性。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。这些互补突变应该允许我们确定AL是否参与自发再激活和/或毒性，或者是否两种表型都是由LAT引起的。这一信息对于开发减少复发性病毒再激活的新策略至关重要，从而减少HSV-1引起的眼病。

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.