Murine Norovirus Transcytosis across an In Vitro Polarized Murine Intestinal Epithelial Monolayer Is Mediated by M-Like Cells
Murine Norovirus Transcytosis across an In Vitro Polarized Murine Intestinal Epithelial Monolayer Is Mediated by M-Like Cells
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DOI：
10.1128/jvi.02378-13
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发表时间：
2013-12-01
影响因子：
5.4
通讯作者：
Wobus, Christiane E.
中科院分区：
文献类型：
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作者：
Gonzalez-Hernandez, Mariam B.;Liu, Thomas;Wobus, Christiane E.
诺如病毒（NoV）是全球绝大多数非细菌性胃肠炎的病原体。由于无法培养人NoV，也无法口服感染小动物模型，因此对病毒进入的初始步骤知之甚少。一个尚不清楚的具体步骤是NoV如何突破肠上皮屏障。鼠NoV（MNV）是唯一可以通过感染鼠巨噬细胞和树突状细胞在体外繁殖的NoV，使得该病毒成为用于研究NoV生物学的不同方面的有吸引力的模型。极化的小鼠肠上皮mIC（cl2）细胞用于研究MNV如何与肠上皮相互作用并穿过肠上皮。在卵泡相关上皮（FAE）的体外模型中，MNV在不存在病毒复制或具有微折叠（M）细胞特性的不同上皮细胞破坏紧密连接的情况下转运穿过极化细胞单层。除了运输MNV，这些M样细胞还转胞质微珠并表达伊加受体。有趣的是，B骨髓瘤细胞培养的基底外侧室下的上皮单层并没有改变M样细胞的数量，但增加了他们的转胞吞活性。我们的数据表明，在体外，MNV可以通过劫持M样细胞的内在转胞途径穿过完整的肠上皮单层，并提出了MNV进入宿主的潜在机制。
Noroviruses (NoVs) are the causative agent of the vast majority of nonbacterial gastroenteritis worldwide. Due to the inability to culture human NoVs and the inability to orally infect a small animal model, little is known about the initial steps of viral entry. One particular step that is not understood is how NoVs breach the intestinal epithelial barrier. Murine NoV (MNV) is the only NoV that can be propagated in vitro by infecting murine macrophages and dendritic cells, making this virus an attractive model for studies of different aspects of NoV biology. Polarized murine intestinal epithelial mIC(cl2) cells were used to investigate how MNV interacts with and crosses the intestinal epithelium. In this in vitro model of the follicle-associated epithelium (FAE), MNV is transported across the polarized cell monolayer in the absence of viral replication or disruption of tight junctions by a distinct epithelial cell with microfold (M) cell properties. In addition to transporting MNV, these M-like cells also transcytose microbeads and express an IgA receptor. Interestingly, B myeloma cells cultured in the basolateral compartment underlying the epithelial monolayer did not alter the number of M-like cells but increased their transcytotic activity. Our data demonstrate that MNV can cross an intact intestinal epithelial monolayer in vitro by hijacking the M-like cells' intrinsic transcytotic pathway and suggest a potential mechanism for MNV entry into the host.