Ocular HSV-1: Preventing Recurrent Corneal Disease

University Of California Irvine, Irvine CA

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Abstract

DESCRIPTION (provided by applicant): Recurrent herpes simplex virus type 1 (HSV-1) infection is a major cause of corneal blindness due to an infectious agent. Since over 80% of adults in the US harbor latent HSV, at this time a therapeutic treatment to prevent recurrent disease in latently infected individuals may be even more beneficial than a prophylactic treatment to prevent acquisition. Recently, a specific form of high intensity magnetic ion impulses (HIMII) appeared to prevent future HSV-1 recurrences in three of three individuals with a history of severe oral HSV-1 recurrences. Noninvasive HIMII can induce electrical current in neurons in vivo thus affecting their activity. Since neuronal HSV-1 latency is regulated at least in part by the neuron, it is logical that HIMII could affect the HSV-1 latency reactivation cycle. In addition to preventing clinical recurrences, the HIMII treatment also reduced anti-HSV serum antibody titers in all three subjects, from very high prior to treatment to below detectable levels one year after treatment. Since we recently showed that decreasing antibody titers are indicative of greatly reduced reactivation this finding argues against a simple placebo effect being responsible for the reduced clinical recurrences. We hypothesize that treatment with high intensity magnetic ion impulses (HIMII) can significantly decrease spontaneous reactivation in eyes of rabbits latently infected with HSV-I. Our Specific Aims include: (1)Confirm that HIMII treatment will significantly reduce spontaneous reactivation in the rabbit eye model. Virus shedding, recurrent eye disease, and anti-HSV-1 antibody titers will all be examined. (2)Test the hypothesis that HIMII treatment decreases spontaneous reactivation by decreasing the amount of latent HSV-1 in rabbit trigeminal ganglia. At various times after treatment the amount of latency will be determined using molecular techniques including in situ hybridization and in situ PCR to determine the relative number of latently infected neurons, and laser capture microdissection followed by real time PCR to determine the amount of latent virus in individual neurons. (3) Determine the optimal HIMII treatment regimen required for optimal suppression of HSV-1 spontaneous reactivation.