HSV-1 GENE EXPRESSION IN LATENCY INFECTED NEURONS

描述（改编自申请人的摘要）：疱疹复发 单纯病毒感染折磨着数百万美国人。 复发性 感染也是传染性病毒的一个重要来源。 临床疾病在免疫功能低下的患者中尤为重要 以及分娩时的复发。 申请人建议使用鼠标 足垫模型的建立是研究重大分子事件的基础， 单纯疱疹病毒周期的维持和再激活阶段。 的 体内研究集中在LAT帽区和LAT启动子，这是 仅启动子在潜伏感染中有活性。 这些研究包括 小鼠神经元特异性转录机制 组织以及负责保持LAT启动子 在所有其他启动子关闭时的潜伏期内激活。 的研究 LAT内含子将进一步证明这种RNA的分子性质，包括 通过剪接信号的突变进一步证明它是内含子。 其他实验可能会提供一些关于为什么它如此稳定的见解。 一 病毒生命周期在生产性和潜伏性之间的根本转换 感染可能发生在感染的早期阶段。 几 建议进行研究以确定是否存在位点特异性抑制或 这些基因在潜伏感染的神经元中失活。

DESCRIPTION (Adapted from Applicant's Abstract): Recurrences of herpes simplex virus infections afflict millions of Americans. Recurrent infections also serve as an important source of communicable virus. Clinical disease is especially important in the immunocompromised patients and in recurrences during childbirth. The applicant proposes to use a mouse foot pad model to study significant molecular events in the establishment, maintenance and reactivation phases of the herpes simplex virus cycle. The in vivo studies focus on the LAT cap region and LAT promoter, which is the only promoter active in latent infection. These studies include the specific mechanism for neuronal specific transcription in mouse neural tissues as well as the mechanism responsible for keeping the LAT promoter active during latency when all other promoters are shut off. Studies on the LAT intron will further document the molecular nature of this RNA including additional proofs that it is an intron by mutation of the splicing signals. Other experiments may provide some insight into why it is so stable. A fundamental switch in the virus life cycle between productive and latent infections may occur at the immediate-early stage of infection. Several studies are proposed to determine if there is site specific repression or inactivation of those genes in latently infected neurons.