LATENT VIRUS INFECTION AND REACTIVATION

潜伏病毒感染和重新激活

• 批准号: 2263941
• 负责人: Richard B. Tenser
• 金额: $ 15.23万
• 依托单位: PENNSYLVANIA STATE UNIV HERSHEY MED CTR
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-07-01 至 1996-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2263941
• 关键词: Alphaherpesvirinae; denervation; ganglions; genetic manipulation; genetic transcription; herpes simplex virus 1; herpes simplex virus 2; host organism interaction; in situ hybridization; laboratory mouse; latent virus infection; neurobiology; neurons; neuropeptides; tissue /cell culture; transplantation; virus cytopathogenic effect; virus genetics; virus infection mechanism; virus replication

Herpes simplex virus (HSV) latency has been well characterized as an infection of the human nervous system, usually of sensory ganglion neurons. Latent HSV infections are the substrate of recurrent HSV infections and possibly other illnesses as well. Mechanisms for the establishment of HSV latency and reactivation of infection in neurons are largely unknown. In order to establish HSV latency, it is likely that the lytic HSV cascade need be diminished. It is hypothesized that this may be achieved partially by neuron-specific transcription regulators. Similar factors are likely to be involved in the reactivation process in latently infected neurons, since it is improbable that many neurons are destroyed by reactivation, although infectious virus is synthesized. HSV latency will be investigated in newborn mice, after neurectomy and in ganglion transplants, situations which are expected to alter neuronal transcription mechanisms. HSV RNA transcription will be studied by in situ and blot hybridization. Similarly, cellular transcriptional regulators of potential importance in control of the lytic infection will be studied by these techniques. Newly developed ganglion transplantation techniques will be utilized to investigate the molecular pathogenesis of HSV latency in terms of host factors and pharmacological agents that may interfere with the establishment of latency. Lastly, we will evaluate the likely non-neuronal site of at least some HSV latency and the effect of HSV infection on ganglion neuron function in studies of neuropeptide expression. HSV infection clearly alters in vivo neuronal function, although this has been uncommonly studied. These investigations will provide insights to the molecular and cellular basis of HSV latency, as well as an understanding altered neuronal functioning which results from HSV infection.

单纯疱疹病毒（HSV）潜伏期已被很好地表征为 人类神经系统的感染，通常是感觉神经节神经元。 潜伏性HSV感染是复发性HSV感染的底物， 可能还有其他疾病。 建立HSV的机制 神经元中感染的潜伏期和再激活在很大程度上是未知的。 在 为了建立HSV潜伏期，很可能裂解性HSV级联反应 需要减少。 据推测，这可能部分实现 由神经元特异性转录调节子控制 类似的因素可能会 参与潜伏感染神经元的再激活过程， 许多神经元不太可能被重新激活所破坏，尽管 感染性病毒是合成的。 HSV潜伏期将在 新生小鼠，神经切除术后和神经节移植，情况 预期其改变神经元转录机制。 将通过原位杂交和印迹杂交研究HSV RNA转录。 类似地，细胞转录调节因子的潜在重要性， 将通过这些技术研究对溶菌感染的控制。 新 将利用发达的神经节移植技术， 从宿主的角度探讨HSV潜伏期的分子发病机制 因素和药理学试剂，可能会干扰 建立潜伏期。 最后，我们将评估可能的非神经元 至少一些HSV潜伏期的部位和HSV感染对 神经节神经元功能的研究神经肽的表达。 HSV 感染明显地改变了体内神经元功能，尽管这已经被 不寻常的研究。 这些研究将为分子和细胞 HSV潜伏期的基础，以及对神经元改变的理解， 这是由HSV感染引起的。