Human noroviruses (HuNoVs) are a major cause of diarrheal disease, yet critical aspects of their biology, including cellular tropism, remain unclear. Although research has traditionally focused on the intestinal epithelium, the hypothesis that HuNoV infects macrophages has been recurrently discussed and is investigated here using a zebrafish larval model. Through single-cell RNA sequencing of dissected zebrafish intestines, we unbiasedly identified macrophages as host cells for HuNoV replication, with all three open reading frames mapped to individual macrophages. Notably, HuNoV preferentially infects actively phagocytosing inflammatory macrophages. HuNoV capsid proteins and double-stranded RNA colocalized within intestinal macrophages of infected zebrafish larvae, and the negative-strand RNA intermediate was detected within FACS-sorted macrophages. Flow cytometry confirmed viral replication within these macrophages, constituting approximately 23% of HuNoV's host cells. Identifying macrophages as host cells prompts a reevaluation of their role in HuNoV pathogenesis, offering new directions for understanding and controlling this infection.

中文翻译：

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斑马鱼肠道的转录分析确定巨噬细胞是人类诺如病毒感染的宿主细胞。


人类诺如病毒 （HuNoV） 是腹泻病的主要原因，但其生物学的关键方面，包括细胞嗜性，仍不清楚。尽管传统上研究集中在肠上皮上，但 HuNoV 感染巨噬细胞的假设已被反复讨论，并在此处使用斑马鱼幼虫模型进行研究。通过对解剖的斑马鱼肠道进行单细胞 RNA 测序，我们无偏倚地将巨噬细胞确定为 HuNoV 复制的宿主细胞，所有三个开放阅读框都映射到单个巨噬细胞。值得注意的是，HuNoV 优先感染主动吞噬炎性巨噬细胞。HuNoV 衣壳蛋白和双链 RNA 共定位于感染斑马鱼幼虫的肠道巨噬细胞内，负链 RNA 中间体在 FACS 分选的巨噬细胞内检测到。流式细胞术证实了这些巨噬细胞内的病毒复制，约占 HuNoV 宿主细胞的 23%。将巨噬细胞识别为宿主细胞可促使重新评估它们在 HuNoV 发病机制中的作用，为理解和控制这种感染提供新的方向。