人类沙斑病毒(HuSaVs),像人类诺如病毒(HuNoV),属于杯状病毒科,可引起人类急性胃肠炎。自1976年发现以来,直到2020年,许多在体外培养HuSaV的尝试都没有成功,当时据报道这些病毒在十二指肠癌细胞源细胞系中复制。允许病毒复制的生理细胞模型对于研究HuSaV生物学和复制机制(如遗传易感性)至关重要。制约因素,和对感染的免疫反应。在这项研究中,我们证明了两种HuSaV毒株在已知支持HuNoV和其他人类肠道病毒复制的人类肠道类肠(HIE)中的复制。HuSaVs在源自空肠的分化HIE中复制,十二指肠和回肠,但不是来自结肠,和胆汁酸是必需的。感染后2小时至3至6天,病毒RNA水平从0.5增加到1.8log10倍。重要的是,HuSaV能够在HIE中复制,而与分泌状态和组织血型抗原表达无关。HIE模型支持HuSaV复制,并允许更好地理解宿主-病原体机制,如细胞嗜性和病毒复制机制。重要性人类沙泊病毒(HuSaVs)是急性胃肠炎的常见但被忽视的原因,尤其是儿童。对这种病原体知之甚少,直到最近才报道其成功的体外培养,在癌细胞来源的细胞系中。这里,我们评估了HuSaV在人类肠道类肠(HIE)中的复制,它们是最初源自人类肠道干细胞的非转化培养物,可以在体外生长,并且已知允许其他肠道病毒的复制。用属于不同基因型病毒的两种菌株成功感染HIE,从而发现这些HuSaV的嗜性仅限于小肠。不会发生在结肠中,和复制需要胆汁酸,但与组织血型抗原的表达无关。因此,HIE代表了进一步研究HuSaV生物学的生理相关模型,也是未来开发疫苗和抗病毒药物的合适平台。
Human sapoviruses (HuSaVs), like human noroviruses (HuNoV), belong to the Caliciviridae family and cause acute gastroenteritis in humans. Since their discovery in 1976, numerous attempts to grow HuSaVs in vitro were unsuccessful until 2020, when these viruses were reported to replicate in a duodenal cancer cell-derived line. Physiological cellular models allowing viral replication are essential to investigate HuSaV biology and replication mechanisms such as genetic susceptibility, restriction factors, and immune responses to infection. In this study, we demonstrate replication of two HuSaV strains in human intestinal enteroids (HIEs) known to support the replication of HuNoV and other human enteric viruses. HuSaVs replicated in differentiated HIEs originating from jejunum, duodenum and ileum, but not from the colon, and bile acids were required. Between 2h and 3 to 6 days postinfection, viral RNA levels increased up from 0.5 to 1.8 log10-fold. Importantly, HuSaVs were able to replicate in HIEs independent of their secretor status and histo-blood group antigen expression. The HIE model supports HuSaV replication and allows a better understanding of host-pathogen mechanisms such as cellular tropism and mechanisms of viral replication. IMPORTANCE Human sapoviruses (HuSaVs) are a frequent but overlooked cause of acute gastroenteritis, especially in children. Little is known about this pathogen, whose successful in vitro cultivation was reported only recently, in a cancer cell-derived line. Here, we assessed the replication of HuSaV in human intestinal enteroids (HIEs), which are nontransformed cultures originally derived from human intestinal stem cells that can be grown in vitro and are known to allow the replication of other enteric viruses. Successful infection of HIEs with two strains belonging to different genotypes of the virus allowed discovery that the tropism of these HuSaVs is restricted to the small intestine, does not occur in the colon, and replication requires bile acid but is independent of the expression of histo-blood group antigens. Thus, HIEs represent a physiologically relevant model to further investigate HuSaV biology and a suitable platform for the future development of vaccines and antivirals.