Interferon lambda (IFN-λ) efficiently blocks norovirus transmission in a mouse model
Interferon lambda (IFN-λ) efficiently blocks norovirus transmission in a mouse model
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DOI：
10.1016/j.antiviral.2017.10.017
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发表时间：
2018-01-01
影响因子：
7.6
通讯作者：
Neyts, Johan
中科院分区：
文献类型：
--
作者：
Rocha-Pereira, Joana;Jacobs, Sophie;Neyts, Johan
人类诺如病毒在人与人之间传播效率很高，因此与急性肠胃炎的爆炸性暴发有关。疫情控制仅限于消毒和隔离措施。应该制定控制诺如病毒传播的策略，研究诺如病毒传播的模型将极大地促进这一点。本研究采用小鼠-小鼠传播模型，在该模型中，小鼠发生急性小鼠诺如病毒（MNV）诱导的腹泻，以探索干扰素lambda （IFN-lambda）在控制诺如病毒感染中的作用。前哨AG129小鼠（缺乏ifn - α / β和ifn - γ受体）与mnv感染的小鼠共同饲养，在其粪便中释放大量病毒，发生mnv感染并伴有腹泻。用IFN-lambda表达质粒接种这些前哨小鼠导致循环IFN-lambda的产生和肠道ifn刺激基因（ISGs）的表达上调。将表达ifn -lambda的质粒注射到哨兵细胞中，可防止MNV感染小鼠暴露于MNV诱导的疾病，以及MNV在小肠中的复制、相关炎症迹象和特异性igg免疫反应的增加。这表明IFN-lambda可以单独介导对诺如病毒传播的保护。开发一种简单的IFN-lambda给药方法可以作为控制诺如病毒爆发和保护老年人和免疫功能低下等弱势群体的一种策略。
Human noroviruses are highly efficient in person to person transmission thus associated with explosive outbreaks of acute gastroenteritis. Outbreak control is limited to disinfection and isolation measures. Strategies to control the spread of noroviruses should be developed and models to study norovirus transmission will greatly facilitate this. Here, a mouse-to-mouse transmission model, in which mice develop acute murine norovirus (MNV)-induced diarrhea, was used to explore the role of interferon lambda (IFN-lambda) in the control of a norovirus infection.Sentinel AG129 mice [deficient in IFN-alpha/beta and IFN-gamma receptors] that were co-housed with MNV-infected mice shedding high amounts of virus in their stool, developed a MNV-infection with associated diarrhea. Inoculation of such sentinel mice with an IFN-lambda expression plasmid resulted in the production of circulating IFN-lambda and upregulation of the expression of IFN-stimulated genes (ISGs) of the gut. Injection of the IFN-lambda-expressing plasmid to sentinels prevents MNV-induced disease upon exposure to MNV-infected mice, as well as MNV replication in the small intestine, the associated signs of inflammation and the mounting of a specific IgG-based immune response. This demonstrates that IFN-lambda can alone mediate protection against transmission of norovirus. The development of a simple delivery method for IFN-lambda could be explored as a strategy to control norovirus outbreaks and protect vulnerable populations such as the elderly and immunocompromised.