Lee Chen-Hsuin, Grey Finn
Division of Infection and Immunity, Roslin Institute, The University of Edinburgh, Edinburgh, United Kingdom.
Front Cell Infect Microbiol. 2020 Jun 10;10:280. doi: 10.3389/fcimb.2020.00280. eCollection 2020.
Human Cytomegalovirus (HCMV) is a highly prevalent herpesvirus, persistently infecting between 30 and 100% of the population, depending on socio-economic status (Fields et al., 2013). HCMV remains an important clinical pathogen accounting for more than 60% of complications associated with solid organ transplant patients (Kotton, 2013; Kowalsky et al., 2013; Bruminhent and Razonable, 2014). It is also the leading cause of infectious congenital birth defects and has been linked to chronic inflammation and immune aging (Ballard et al., 1979; Griffith et al., 2016; Jergovic et al., 2019). There is currently no effective vaccine and HCMV antivirals have significant side effects. As current antivirals target viral genes, the virus can develop resistance, reducing drug efficacy. There is therefore an urgent need for new antiviral agents that are effective against HCMV, have better toxicity profiles and are less vulnerable to the emergence of resistant strains. Targeting of host factors that are critical to virus replication is a potential strategy for the development of novel antivirals that circumvent the development of viral resistance. Systematic high throughput approaches provide powerful methods for the identification of novel host-virus interactions. As well as contributing to our basic understanding of virus and cell biology, such studies provide potential targets for the development of novel antiviral agents. High-throughput studies, such as RNA sequencing, proteomics, and RNA interference screens, are useful tools to identify HCMV-induced global changes in host mRNA and protein expression levels and host factors important for virus replication. Here, we summarize new findings on HCMV lytic infection from high-throughput studies since 2014 and how screening approaches have evolved.
人类巨细胞病毒（HCMV）是一种高度流行的疱疹病毒，根据社会经济状况，持续感染30%至100%的人群（菲尔兹等人，2013年）。HCMV仍然是一种重要的临床病原体，占实体器官移植患者相关并发症的60%以上（科顿，2013年；科瓦尔斯基等人，2013年；布鲁明赫特和拉佐纳布尔，2014年）。它也是传染性先天性出生缺陷的主要原因，并与慢性炎症和免疫衰老有关（巴拉德等人，1979年；格里菲思等人，2016年；耶尔戈维奇等人，2019年）。目前尚无有效的疫苗，HCMV抗病毒药物有显著的副作用。由于目前的抗病毒药物靶向病毒基因，病毒会产生耐药性，降低药物疗效。因此，迫切需要新的抗病毒药物，它们对HCMV有效，具有更好的毒性特征，并且不易出现耐药菌株。靶向对病毒复制至关重要的宿主因子是开发新型抗病毒药物以规避病毒耐药性发展的潜在策略。系统的高通量方法为鉴定新型宿主-病毒相互作用提供了有力手段。这些研究不仅有助于我们对病毒和细胞生物学的基本理解，还为新型抗病毒药物的开发提供了潜在靶点。高通量研究，如RNA测序、蛋白质组学和RNA干扰筛选，是识别HCMV诱导的宿主mRNA和蛋白质表达水平的全局变化以及对病毒复制重要的宿主因子的有用工具。在这里，我们总结了自2014年以来高通量研究中关于HCMV裂解感染的新发现以及筛选方法是如何演变的。
