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Bright and Early: Inhibiting Human Cytomegalovirus by Targeting Major Immediate-Early Gene Expression or Protein Function.
Viruses ( IF 3.8 ) Pub Date : 2020-01-16 , DOI: 10.3390/v12010110
Catherine S Adamson 1 , Michael M Nevels 1
Affiliation  

The human cytomegalovirus (HCMV), one of eight human herpesviruses, establishes lifelong latent infections in most people worldwide. Primary or reactivated HCMV infections cause severe disease in immunosuppressed patients and congenital defects in children. There is no vaccine for HCMV, and the currently approved antivirals come with major limitations. Most approved HCMV antivirals target late molecular processes in the viral replication cycle including DNA replication and packaging. "Bright and early" events in HCMV infection have not been exploited for systemic prevention or treatment of disease. Initiation of HCMV replication depends on transcription from the viral major immediate-early (IE) gene. Alternative transcripts produced from this gene give rise to the IE1 and IE2 families of viral proteins, which localize to the host cell nucleus. The IE1 and IE2 proteins are believed to control all subsequent early and late events in HCMV replication, including reactivation from latency, in part by antagonizing intrinsic and innate immune responses. Here we provide an update on the regulation of major IE gene expression and the functions of IE1 and IE2 proteins. We will relate this insight to experimental approaches that target IE gene expression or protein function via molecular gene silencing and editing or small chemical inhibitors.

中文翻译:

Bright and Early:通过靶向主要的即早基因表达或蛋白质功能来抑制人类巨细胞病毒。

人类巨细胞病毒 (HCMV) 是八种人类疱疹病毒之一,它在全世界大多数人中建立了终生潜伏感染。原发性或再激活的 HCMV 感染会导致免疫抑制患者的严重疾病和儿童的先天性缺陷。没有针对 HCMV 的疫苗,目前批准的抗病毒药物有很大的局限性。大多数批准的 HCMV 抗病毒药物针对病毒复制周期中的晚期分子过程,包括 DNA 复制和包装。HCMV 感染中的“明亮和早期”事件尚未被用于系统性预防或治疗疾病。HCMV 复制的启动取决于病毒主要即早 (IE) 基因的转录。从该基因产生的替代转录物产生病毒蛋白的 IE1 和 IE2 家族,定位于宿主细胞核。IE1 和 IE2 蛋白被认为控制 HCMV 复制中所有随后的早期和晚期事件,包括潜伏期的重新激活,部分通过拮抗内在和先天免疫反应。在这里,我们提供了有关主要 IE 基因表达调控以及 IE1 和 IE2 蛋白功能的最新信息。我们将把这一见解与通过分子基因沉默和编辑或小型化学抑制剂靶向 IE 基因表达或蛋白质功能的实验方法联系起来。在这里,我们提供了有关主要 IE 基因表达调控以及 IE1 和 IE2 蛋白功能的最新信息。我们将把这一见解与通过分子基因沉默和编辑或小型化学抑制剂靶向 IE 基因表达或蛋白质功能的实验方法联系起来。在这里,我们提供了有关主要 IE 基因表达调控以及 IE1 和 IE2 蛋白功能的最新信息。我们将把这一见解与通过分子基因沉默和编辑或小型化学抑制剂靶向 IE 基因表达或蛋白质功能的实验方法联系起来。
更新日期:2020-01-16
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