Department of Medicine, Washington University School of Medicine, Saint Louis, MO, USA.
Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO, USA.
Nat Microbiol. 2019 Jul;4(7):1120-1128. doi: 10.1038/s41564-019-0416-7. Epub 2019 Apr 1.
Commensal microbes profoundly impact host immunity to enteric viral infections. We have shown that the bacterial microbiota and host antiviral cytokine interferon-λ (IFN-λ) determine the persistence of murine norovirus in the gut. However, the effects of the virome in modulating enteric infections remain unexplored. Here, we report that murine astrovirus can complement primary immunodeficiency to protect against murine norovirus and rotavirus infections. Protection against infection was horizontally transferable between immunocompromised mouse strains by co-housing and fecal transplantation. Furthermore, protection against enteric pathogens corresponded with the presence of a specific strain of murine astrovirus in the gut, and this complementation of immunodeficiency required IFN-λ signalling in gut epithelial cells. Our study demonstrates that elements of the virome can protect against enteric pathogens in an immunodeficient host.
共生微生物对宿主肠道病毒感染的免疫有深远影响。我们已经表明，细菌微生物群和宿主抗病毒细胞因子干扰素-λ（IFN-λ）决定了肠道内鼠诺如病毒的持续存在。然而，病毒组在调节肠道感染方面的作用仍未得到探索。在这里，我们报告说，鼠星状病毒可以补充原发性免疫缺陷，以预防鼠诺如病毒和轮状病毒感染。通过共同饲养和粪便移植，免疫功能低下的小鼠之间可以进行水平转移，从而获得对感染的保护。此外，针对肠道病原体的保护与肠道中特定株鼠星状病毒的存在相对应，而这种免疫缺陷的补充需要肠道上皮细胞中的 IFN-λ 信号转导。我们的研究表明，病毒组的某些成分可以在免疫缺陷宿主中保护其免受肠道病原体的侵害。
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