CRISPR/Cas9在EB病毒感染免疫中的研究进展

Research progress of CRISPR-Cas9 genetic technology in immunity of Epstein-Barr virus infection

摘要:

爱泼斯坦巴尔病毒(Epstein-Barr virus，EBV)人群感染率高，不同地区、不同年龄人群感染后引发疾病类型各异，除少数急性感染者可自愈外，大部分慢性和潜伏感染者迁延不愈，而且具有潜在的致癌风险；目前机体感染EBV后的免疫机制仍不明确，临床上缺乏有效的治疗药物和根治措施，总体预后较差。作为第三代基因编辑工具，成簇的规律间隔短回文重复序列及相关核酸酶9 (clustered regular interspaced short palindromic repeats/CRISPR-associated nuclease 9，CRISPR/Cas9)技术可在向导RNA引导下，对目的基因组序列进行靶向编辑。因其操作简便、经济高效，目前已广泛应用于农作物品种改良、动物疾病模型构建以及人类疾病精准诊治等领域。本文介绍了CRISPR/Cas9技术应用于EBV感染免疫研究的最新进展，包括EBV致病基因亚型和宿主依赖基因筛选，关键致病机制探索以及基因靶向编辑治疗EBV相关疾病等，为阐明EBV相关疾病的发病机制和探索新型抗病毒治疗策略提供理论依据。

Abstract:

Epstein-Barr virus (EBV) infects the vast majority of the world’s population. The types of diseases, caused by infection of Epstein-Barr virus, in different subgroups and regions are various. However, the immune mechanism of EBV infection is still unclear. Acute EB virus infection related diseases are usually self-healing. On the other hand, most patients with chronic and latent infections are still lack of effective treatment with a poor prognosis, and risk of cancer. The CRISPR/Cas9 (clustered regular interspaced short palindromic repeats/CRISPR-associated nuclease 9) technology was derived from an acquired immune defense system in bacteria and archaea. As the third-generation genomic editing technology, it can perform targeted editing of specific genomic sequences under the guidance of sgRNA. Because of its characteristics of ease to operation, time saving and high efficiency, it has been widely used in new crop cultivation, animal disease model construction and precise diagnosis and treatment of human diseases. The review describes the progression of CRISPR/Cas9 system in immune research of EB virus infection, including exploration of screening key pathogenic genes and host dependency factors, pathogenic mechanisms, and gene targeted editing to treat EBV-related diseases. It provides implications for studying the pathogenesis of Epstein-Barr virus related diseases and exploring new antiviral treatment strategy.