Sion Emilly, Ab-Rahim Sharaniza, Muhamad Mudiana
Department of Biochemistry and Molecular Medicine, Faculty of Medicine, Universiti Teknologi MARA, Selangor Branch, Sungai Buloh Campus, Sungai Buloh 47000, Selangor, Malaysia.
Life (Basel). 2023 Jun 26;13(7):1447. doi: 10.3390/life13071447.
Most acute gastroenteritis (AGE) outbreaks and sporadic cases in developing countries are attributable to infection by human norovirus (HuNoV), the enteric virus mainly transmitted via fecal-contaminated water. However, it has been challenging to study HuNoV due to the lack of suitable systems to cultivate and replicate the virus, hindering the development of treatments and vaccines. Researchers have been using virus-like particles (VLPs) and infectious viral clones to overcome this challenge as alternatives to fresh virus isolates in various in vitro and ex vivo models. VLPs are multiprotein structures that mimic the wild-type virus but cannot replicate in host cells due to the lack of genetic materials for replication, limiting downstream analysis of the virus life cycle and pathogenesis. The development of in vitro cloning systems has shown promise for HuNoV replication studies. This review discusses the approaches for constructing HuNoV-VLPs and infectious viral clones, the techniques involved, and the challenges faced. It also highlights the relationship between viral genes and their protein products and provides a perspective on technical considerations for producing efficient HuNoV-VLPs and infectious viral clones, which could substitute for native human noroviruses in future studies.
在发展中国家，大多数急性胃肠炎（AGE）暴发和散发病例是由人诺如病毒（HuNoV）感染所致，这种肠道病毒主要通过粪便污染的水传播。然而，由于缺乏合适的病毒培养和复制系统，对HuNoV的研究一直具有挑战性，这阻碍了治疗方法和疫苗的开发。研究人员一直在使用病毒样颗粒（VLP）和感染性病毒克隆来克服这一挑战，作为各种体外和体内模型中新鲜病毒分离株的替代物。VLP是多蛋白结构，模仿野生型病毒，但由于缺乏用于复制的遗传物质，无法在宿主细胞中复制，限制了对病毒生命周期和发病机制的下游分析。体外克隆系统的发展为HuNoV复制研究带来了希望。本综述讨论了构建HuNoV-VLP和感染性病毒克隆的方法、所涉及技术以及面临的挑战。它还强调了病毒基因与其蛋白质产物之间的关系，并对生产高效HuNoV-VLP和感染性病毒克隆的技术考虑因素提供了一个视角，这些克隆在未来研究中可替代天然人诺如病毒。
