Persistent viral infections result from evasion or avoidance of sterilizing immunity, extend the timeframe of virus transmission, and can trigger disease. Prior studies in mouse models of persistent infection have suggested that ineffective adaptive immune responses are necessary for persistent viral infection. However, recent work in the murine norovirus (MNV) model of persistent infection demonstrates that innate immunity can control both early and persistent viral replication independently of adaptive immune effector functions. Interferons (IFNs) are central to the innate control of persistent MNV, apart from a role in modulating adaptive immunity. Furthermore, subtypes of IFN play distinct tissue-specific roles in innate control of persistent MNV infection. Type I IFN (IFN-α/β) controls systemic replication, and type III IFN (IFN-λ) controls MNV persistence in the intestinal epithelium. In this article, we review recent findings in the MNV model, highlighting the role of IFNs and innate immunity in clearing persistent viral infection, and discussing the broader implications of these findings for control of persistent human infections.

持续的病毒感染是由规避或避免灭菌免疫所致，延长了病毒传播的时间，并可能引发疾病。先前在持续感染的小鼠模型中的研究表明，无效的适应性免疫反应对于持续的病毒感染是必需的。但是，鼠诺如病毒（MNV）持续感染模型的最新研究表明，先天免疫可以独立于适应性免疫效应器功能控制早期和持续病毒复制。除了在调节适应性免疫中的作用外，干扰素（IFN）对于持久性MNV的先天控制至关重要。此外，IFN的亚型在持久性MNV感染的先天控制中起不同的组织特异性作用。I型干扰素（IFN-α/β）控制着系统性复制，III型IFN（IFN-λ）控制MNV在肠道上皮细胞中的持久性。在本文中，我们回顾了MNV模型中的最新发现，重点介绍了IFN和先天免疫在清除持续性病毒感染中的作用，并讨论了这些发现对控制人类持续感染的更广泛意义。