Human Cytomegalovirus Latency: Targeting Differences in the Latently Infected Cell with a View to Clearing Latent Infection

E. Poole, M. Wills, J. Sinclair
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引用次数: 30

Abstract

Human cytomegalovirus (HCMV) is a human herpesvirus which causes little or no disease in the immunocompetent. However, in immunocompromised individuals, neonates, or patients on immune suppressive therapies, HCMV can cause significant morbidity and mortality in some patient groups. As with all herpesviruses, HCMV has two life cycle phases: a productive phase, where new virions are produced and a latent phase where there is a restricted gene transcription profile and no new virion production. Currently available antivirals target the productive phase of HCMV infection and, although these have greatly decreased the severity of HCMV-induced disease in immunocompromised or immunosuppressed individuals, they often have associated toxicities, routinely result in selection of drug resistant viral mutants, and, importantly, they do not target cells latently infected with virus. Thus, there is a real need to derive novel antiviral therapies which, not least, are also able to target latent infection. In this paper, we describe recent work which has begun to analyse changes in the cell associated with latent infection and the possibility that these latency-associated changes in cell phenotype could be targeted by novel chemo- or immunotherapeutic strategies in order to diminish, or even clear, latent infection at least in some specific clinical settings.
人巨细胞病毒潜伏期:潜伏感染细胞的靶向差异与清除潜伏感染的观点
人巨细胞病毒(HCMV)是一种人类疱疹病毒,在免疫正常的人群中很少或不会引起疾病。然而,在免疫功能低下的个体、新生儿或接受免疫抑制治疗的患者中,HCMV可在某些患者群体中引起显著的发病率和死亡率。与所有疱疹病毒一样,HCMV有两个生命周期阶段:生产阶段,产生新的病毒粒子;潜伏阶段,基因转录谱受到限制,不产生新的病毒粒子。目前可用的抗病毒药物靶向HCMV感染的生产阶段,尽管这些药物大大降低了免疫功能低下或免疫抑制个体中HCMV诱导疾病的严重程度,但它们通常具有相关毒性,通常导致耐药病毒突变体的选择,重要的是,它们不靶向潜伏感染病毒的细胞。因此,确实需要开发新的抗病毒疗法,尤其是能够靶向潜伏感染的抗病毒疗法。在本文中,我们描述了最近的工作,这些工作已经开始分析与潜伏感染相关的细胞变化,以及这些潜伏相关的细胞表型变化可以通过新的化学或免疫治疗策略来靶向,以便至少在某些特定的临床环境中减少甚至清除潜伏感染。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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