Rotavirus infection of human cholangiocytes parallels the murine model of biliary atresia.
Rotavirus infection of human cholangiocytes parallels the murine model of biliary atresia.
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DOI：
10.1016/j.jss.2012.05.082
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发表时间：
2012-10
期刊：
影响因子：
--
通讯作者：
Tiao G
中科院分区：
文献类型：
--
作者：
Coots A;Donnelly B;Mohanty SK;McNeal M;Sestak K;Tiao G
胆道闭锁（BA）是儿童肝移植的主要指征。小鼠BA模型支持病毒病原学，因为新生小鼠感染恒河轮状病毒（RRV）导致胆道阻塞。病毒感染以胆道上皮为目标，模型的发育依赖于病毒株。目前还没有研究确定人类胆管细胞是否也易受轮状病毒感染。我们利用永生化的人胆管细胞细胞系和从外植肝脏获得的人胆管细胞建立了体外人模型，以确定人胆管细胞对轮状病毒感染的易感性。用六种不同的轮状病毒株在永生化小鼠（mCL）和人（H69）细胞上进行了复制和结合试验。从尸体肝脏中分离出原代人胆管细胞，在培养中进行鉴定，并感染引起小鼠BA的RRV和另一种不引起小鼠BA的类人猿菌株TUCH。永生化小鼠和人胆管细胞表现出与不同轮状病毒株相似的传染性和结合模式。这两种细胞系在RRV感染后产生的病毒产量明显高于其他菌株。在原代人胆管细胞中，细胞角蛋白染色显示其保持上皮特征，RRV复制的产量比TUCH高1000倍。永生化和原代人胆管细胞都易受RRV感染，其方式与小鼠胆管细胞相似。这些新发现提示轮状病毒感染可能在人类BA的发病机制中起潜在作用。
Biliary atresia (BA) is the leading indication for liver transplantation in the pediatric population. The murine model of BA supports a viral etiology as infection of neonatal mice with rhesus rotavirus (RRV) results in biliary obstruction. Viral infection targets the biliary epithelium and development of the model is viral strain dependent. No study has yet determined if human cholangiocytes are also susceptible to rotaviral infection. We established an in vitro human model utilizing an immortalized human cholangiocyte cell line and primary human cholangiocytes obtained from explanted livers to determine human cholangiocyte susceptibility to rotavirus infection. Replication and binding assays were performed on immortalized mouse (mCL) and human (H69) cells using six different strains of rotavirus. Primary human cholangiocytes were isolated from cadaveric livers, characterized in culture, and infected with RRV which causes BA in mice and another simian strain, TUCH which does not cause BA in mice. Immortalized mouse and human cholangiocytes demonstrated similar patterns of infectivity and binding with different strains of rotavirus. Both cell lines produced a significantly higher viral yield with RRV infection than with the other strains tested. In primary human cholangiocytes, which maintained their epithelial characteristics as demonstrated by cytokeratin staining, RRV replicated to a yield 1000 fold higher than TUCH. Both immortalized and primary human cholangiocytes are susceptible to RRV infection in a fashion similar to murine cholangiocytes. These novel findings suggest rotavirus infection could have a potential role in the pathogenesis of human BA.
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