van Diemen Ferdy R, Lebbink Robert Jan
Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands.
Utrecht Cornea Research Group, Department of Ophthalmology, University Medical Center Utrecht, Utrecht, The Netherlands.
Cell Microbiol. 2017 Feb;19(2). doi: 10.1111/cmi.12694. Epub 2016 Dec 23.
Over 90% of the adult population is infected with one or multiple herpesviruses. These viruses are characterized by their ability to establish latency, where the host is unable to clear the invader from infected cells resulting in a lifelong infection. Herpesviruses cause a wide variety of (recurrent) diseases such as cold sores, shingles, congenital defects and several malignancies. Although the productive phase of a herpesvirus infection can often be efficiently limited by nucleoside analogs, these drugs are ineffective during a latent herpesvirus infection and are therefore unable to clear herpesviruses from the human host. Advances in genome engineering using clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 facilitates virus research and may hold potential to treat or cure previously incurable herpesvirus infections by directly targeting these viruses within infected cells. Here, we review recent applications of the CRISPR/Cas9 system for herpesviral research and discuss the therapeutic potential of the system to treat, or even cure, productive and latent herpesviral infections.
超过90%的成年人口感染了一种或多种疱疹病毒。这些病毒的特点是能够建立潜伏期,在此期间宿主无法从受感染细胞中清除入侵者,从而导致终身感染。疱疹病毒会引发多种(复发性)疾病,如唇疱疹、带状疱疹、先天性缺陷和几种恶性肿瘤。尽管疱疹病毒感染的增殖期通常可以通过核苷类似物有效控制,但这些药物在疱疹病毒潜伏感染期间无效,因此无法从人类宿主中清除疱疹病毒。利用成簇规律间隔短回文重复序列(CRISPR)/Cas9进行基因组工程的进展促进了病毒研究,并可能通过直接靶向受感染细胞内的这些病毒,为治疗或治愈以前无法治愈的疱疹病毒感染带来潜力。在此,我们综述了CRISPR/Cas9系统在疱疹病毒研究中的最新应用,并讨论了该系统治疗甚至治愈增殖性和潜伏性疱疹病毒感染的治疗潜力。