人诺如病毒培养模型研究进展

Research progress on human norovirus cultivation model

摘要

诺如病毒是引发病毒性腹泻的主要病原体之一。由于缺少理想的体外细胞培养模型和动物模型,人诺如病毒(human norovirus,HuNoV)感染和复制机制、免疫应答、抗病毒药物筛选和疫苗评价等方面的研究均受到了一定阻碍。本文回顾了2003—2025年的相关研究,探讨细胞培养模型和动物模型这2类模型的可行性和优缺点。细胞模型方面,大部分传代细胞系无法支持HuNoV复制,在肠道类器官上培养成功但操作复杂且可能受限于伦理问题。近年来建立的人唾液腺细胞系可稳定支持HuNoV复制,成本低、易操作,成为重要替代体系。在动物模型方面,高昂的试验费用和与自然感染差之甚远的免疫反应限制了动物模型的推广使用。通过本文中对各培养模型的归纳和讨论,期望通过总结前人的研究成果,为改良现有培养模型及探索新培养模型提供方向。

Abstract

Norovirus is one of the main pathogens causing viral diarrhea. Due to the lack of ideal in vitro cell culture models and animal models, research on the mechanisms of human norovirus (HuNoV) infection and replication, immune response, antiviral drug screening, and vaccine evaluation had been hindered. This review covers studies from 2003 to 2025, examining the feasibility, advantages, and limitations of both cell culture models and animal models. For cell models, most immortalized cell lines fail to support HuNoV replication; while intestinal organoids have successfully supported virus culture, the procedure is complex and may face ethical constraints. Human salivary gland cell lines, established in recent years, can stably support HuNoV replication and are low-cost, easy to operate, thus serving as an important alternative system. For animal models, high costs and immune responses that differ markedly from natural infections have limited their widespread use. By the summarizing and discussing these culture models, this review aims to consolidate previous findings and offer directions for improving existing models and developing new ones.

关键词

人诺如病毒 / 细胞模型 / 动物模型 / 人肠道类器官 / 人唾液腺细胞系

Key words

human norovirus / cell models / animal models / human intestinal enteroids / human salivary gland cell lines

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基金资助

药品监管科学全国重点实验室课题:基于类器官技术诺如疫苗有效性和破伤风疫苗安全性质量评价新技术研究(2026SKLDRS03091)