Regulation Of Transcription Of Herpes Simplex Virus

单纯疱疹病毒转录的调控

• 批准号: 8336102
• 负责人: THOMAS M KRISTIE
• 金额: $ 40.5万
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8336102
• 关键词: Afferent Neurons; Animal Model; Biological Models; Cell Culture Techniques; Cell Nucleus; Chromatin; Chromatin Structure; Complex; Cytoplasm; Data; Disease; Genes; Genetic Transcription; Goals; Immediate-Early Proteins; Individual; Lesion; Lytic; Neurons; Process; Proteins; Recruitment Activity; Recurrence; Regulation; Role; Sensory; Simplexvirus; Stimulus; Transcription Coactivator; Viral; Virus; Virus Latency; Work; design; host cell factor C1; inhibitor/antagonist; latent infection; mouse model; nucleocytoplasmic transport; promoter; protein complex; reactivation from latency; response; small molecule

Once an individual is infected with herpes simplex virus (HSV), the virus establishes a latent infection in sensory neurons. Periodically, various stimuli may induce lytic reactivation resulting in mild recurrent lesions to more severe disease. The factors which determine the establishment of latency and reactivation are poorly understood. However, the regulation of this latency-reactivation cycle is dependent upon the components which regulate the expression of the IE genes. The critical component of this regulatory process is HCF-1. Analyses of this protein in a mouse model have shown that the protein is specifically sequestered in the cytoplasm of sensory neurons and rapidly transported to the nucleus in response to reativation stimuli. Recent work has resulted in the establishment of a primary sensory neuronal cell culture which allowed for the specific localization of HCF-1 in the cytoplasm. Additional studies have determined that the nuclear transport of HCF-1 in latently infected neurons correlates with viral reactivation and that HCF-1 is rapidly recruited to the promoters of the viral IE genes upon initiation of reactivation. Data also suggests that HCF-1 modulates viral chromatin structure to initiate viral reactivation from latency. In 2011, studies in animal model systems of viral reactivation have demonstrated the utility of small molecule inhibitors of HCF-1 associated chromatin modulation components to block viral reactivation from latency.

一旦一个人感染了单纯疱疹病毒（HSV），该病毒就会在感觉神经元中产生潜在的感染。 周期性地，各种刺激可能引起裂解再活化，从而导致更严重的疾病的轻度复发性病变。 确定延迟和重新激活的因素知之甚少。但是，这种潜伏期反应周期的调节取决于调节IE基因表达的成分。 该调节过程的关键组成部分是HCF-1。 在小鼠模型中对该蛋白的分析表明，该蛋白在感觉神经元的细胞质中特异性隔离，并迅速转移到细胞核中，以响应重新激活刺激。 最近的工作导致建立了主要的感觉神经元细胞培养，该培养可以使HCF-1在细胞质中的特定定位。 其他研究已经确定，在潜在感染的神经元中，HCF-1的核转运与病毒重新激活相关，并且HCF-1在启动重新激活后迅速招募到病毒IE基因的启动子。数据还表明，HCF-1调节病毒染色质结构，以引发潜伏期的病毒重新激活。 2011年，在病毒重新激活的动物模型系统中的研究表明，HCF-1相关的染色质调节成分的小分子抑制剂的实用性以阻止潜伏期的病毒重新激活。