Noroviruses are the leading cause of food-borne gastroenteritis outbreaks and childhood diarrhoea globally, estimated to be responsible for 200,000 deaths in children each year ^1-4 . Thus, reducing norovirus-associated disease is a critical priority. Development of vaccines and therapeutics has been hindered by the limited understanding of basic norovirus pathogenesis and cell tropism. While macrophages, dendritic cells, B cells and stem-cell-derived enteroids can all support infection of certain noroviruses in vitro ^5-7 , efforts to define in vivo norovirus cell tropism have generated conflicting results. Some studies detected infected intestinal immune cells ^8-12 , other studies detected epithelial cells ¹³ , and still others detected immune and epithelial cells ^14-16 . Major limitations of these studies are that they were performed on tissue sections from immunocompromised or germ-free hosts, chronically infected hosts where the timing of infection was unknown, or following non-biologically relevant inoculation routes. Here, we report that the dominant cellular targets of a murine norovirus inoculated orally into immunocompetent mice are macrophages, dendritic cells, B cells and T cells in the gut-associated lymphoid tissue. Importantly, we also demonstrate that a norovirus can infect T cells, a previously unrecognized target, in vitro. These findings represent the most extensive analyses to date of in vivo norovirus cell tropism in orally inoculated, immunocompetent hosts at the peak of acute infection and thus they significantly advance our basic understanding of norovirus pathogenesis.

中文翻译：

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急性诺如病毒感染的主要目标是肠道相关淋巴组织中的免疫细胞。

诺如病毒是全球食源性肠胃炎暴发和儿童腹泻的主要原因，估计每年导致 200,000 名儿童死亡^1-4。因此，减少诺如病毒相关疾病是当务之急。由于对诺如病毒的基本发病机制和细胞嗜性的了解有限，疫苗和疗法的开发受到了阻碍。虽然巨噬细胞、树突细胞、B 细胞和干细胞衍生的肠样细胞都可以在体外支持某些诺如病毒的感染^5-7，但定义体内诺如病毒细胞嗜性的努力却产生了相互矛盾的结果。一些研究检测到受感染的肠道免疫细胞^8-12，其他研究检测到上皮细胞¹³, 还有一些人检测到免疫和上皮细胞^14-16. 这些研究的主要局限性在于，它们是在免疫功能低下或无菌宿主、感染时间未知的慢性感染宿主或遵循非生物学相关接种途径的组织切片上进行的。在这里，我们报告说，将小鼠诺如病毒口服接种到免疫活性小鼠中的主要细胞靶标是肠道相关淋巴组织中的巨噬细胞、树突细胞、B 细胞和 T 细胞。重要的是，我们还证明了诺如病毒可以在体外感染 T 细胞，这是一种以前未被识别的靶标。这些发现代表了迄今为止对急性感染高峰期口服接种的免疫活性宿主体内诺如病毒细胞嗜性的最广泛分析，因此它们显着推进了我们对诺如病毒发病机制的基本理解。