Ocular HSV-1:construction and analysis of AL mutants

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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.