Ocular HSV-1: Preventing Recurrent Corneal Disease

描述（由申请人提供）：复发性单纯疱疹病毒1型（HSV-1）感染是由感染因子引起的角膜失明的主要原因。由于在美国超过80%的成年人潜伏着HSV，在这个时候，预防潜伏感染者复发的治疗可能比预防获得的预防性治疗更有益。最近，一种特殊形式的高强度磁离子脉冲（HIMII）似乎可以预防三名有严重口腔HSV-1复发史的个体中的三名未来HSV-1复发。非侵入性HIMII可以在体内诱导神经元电流从而影响其活动。由于神经元的HSV-1潜伏期至少部分由神经元调节，因此HIMII可能影响HSV-1潜伏期的再激活周期是合乎逻辑的。除了预防临床复发外，HIMII治疗还降低了所有三名受试者的抗hsv血清抗体滴度，从治疗前的很高水平降至治疗后一年的可检测水平以下。由于我们最近表明抗体滴度的降低表明再激活大大减少，这一发现反对简单的安慰剂效应是减少临床复发率的原因。我们假设高强度磁离子脉冲（HIMII）治疗可以显著降低潜伏感染hsv - 1的兔子眼睛的自发再激活。

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.