OCULAR INFECTION WITH THE HERPESVIRUSES

疱疹病毒引起的眼部感染

• 批准号: 2163703
• 负责人: TODD P. MARGOLIS
• 金额: $ 21.02万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-12-01 至 1998-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2163703
• 关键词: biomarker; ganglions; gene expression; genetic transcription; growth factor receptors; herpes simplex virus 1; host organism interaction; immunofluorescence technique; in situ hybridization; interferon gamma; laboratory mouse; latent virus infection; nervous system infection; neurons; neurotrophic factors; neurotropic virus; northern blottings; ocular herpes; phenotype; regulatory gene; transcription factor; trigeminal nerve; virus genetics; virus infection mechanism; virus protein

Recurrent infections with herpes simplex virus (HSV) occur worldwide and may affect up to one-third of the world's population. In addition, recurrent hepatic keratitis is the leading causes of infectious corneal blindness in developed countries. An important concept in understanding the pathophysiology of recurrent hepatic disease is that the virus establishes latent infections in neurons. Primary sensory neurons are the classic reservoirs, but latent infections can also be established in autonomic, motor and a variety of CNS neurons. Periodic reactivation of the latent virus leads to recurrent disease. Although prophylactic antiviral therapy has proven effective in reducing the frequency and severity of recurrent non-ocular disease due to HSV, no therapy has proven effective in eliminating the virus from latently infected neurons. Development of such a therapy will undoubtably depend on an improved understanding of the cellular and molecular basis of latency and reactivation. The goal of our proposed research is to explore the role of host neurons in the regulations of transcription of the HSV genome in vivo as it pertains to the establishment of the latent state. Although work carried out during the last three years has revealed much about the host cell regulation of infection with HSV in transient assays and cell culture lines, very little of this has been validated in vivo. Through the use of genetically engineered viruses, nucleic acid probes and multiple labeling techniques we hope to being to study the role of the host factors in transcriptional regulation of the HSV genome in vivo. We will specifically investigate, on a cell by cell basis, viral gene expression in acutely infected ocular primary sensory neurons in order to study the ability of neuronal sub-populations to differentially regulated the outcome of infection with HSV. In addition we will attempt to correlate the expression of specific host transcriptional regulatory proteins. (Oct-1, Oct-2, trkA, gamma interferon), known to influence viral gene vectors we will attempt to over-express these same 'suspect' host regulatory proteins in acutely infected neurons in order to determine whether these factors are capable of influencing the outcome of viral gene expression in vivo.

单纯疱疹病毒（HSV）的复发性感染在世界范围内发生， 可能会影响到世界上三分之一的人口。 此外，本发明还提供了一种方法， 复发性肝性角膜炎是感染性角膜炎的主要原因 发达国家的失明。 理解中的一个重要概念 复发性肝病的病理生理学是病毒 在神经元中建立潜伏感染。 初级感觉神经元是 典型的水库，但潜伏感染也可以建立在 自主神经元、运动神经元和各种CNS神经元。 定期重新激活 潜伏病毒导致疾病复发。 虽然预防 抗病毒治疗已被证明有效地降低了频率， 由于HSV引起的复发性非眼部疾病的严重程度，没有治疗 被证明能有效清除潜伏感染神经元中的病毒。 这种疗法的发展将必然依赖于一种改进的 了解潜伏期的细胞和分子基础， 重新激活 我们提出的研究目标是探索宿主神经元的作用 在体内HSV基因组转录的调节中， 涉及潜在状态的建立。 虽然工作进行 在过去的三年里，已经揭示了很多关于宿主细胞的信息， 在瞬时测定和细胞培养中调节HSV感染 线，很少有这已经在体内验证。 通过使用 基因工程病毒，核酸探针和多种 我们希望通过标记技术来研究宿主的作用 在HSV基因组的体内转录调节中的因子。 我们将 具体地，在逐个细胞基础上，研究病毒基因表达 在急性感染的眼初级感觉神经元中， 神经元亚群的能力，差异调节 感染HSV的后果 此外，我们还将尝试将 特定宿主转录调节蛋白的表达。 （Oct-1，Oct-2，trkA，γ干扰素），已知影响病毒基因 我们将尝试过度表达这些相同的“可疑”宿主 急性感染神经元中的调节蛋白，以确定 这些因素是否能够影响病毒感染的结果， 体内基因表达。