Rotavirus replication in the cholangiocyte mediates the temporal dependence of murine biliary atresia.
Rotavirus replication in the cholangiocyte mediates the temporal dependence of murine biliary atresia.
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DOI：
10.1371/journal.pone.0069069
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Tiao GM
中科院分区：
文献类型：
--
作者：
Mohanty SK;Donnelly B;Bondoc A;Jafri M;Walther A;Coots A;McNeal M;Witte D;Tiao GM
胆道闭锁(BA)是一种导致胆道树闭塞的新生儿疾病。BA的小鼠模型反映了人类的疾病，是基于新生小鼠感染恒河猴轮状病毒(RRV)，导致阻塞性胆管疾病。这项研究的目的是描述病毒感染和该模型的诱导之间的时间关系。BALB/c小鼠分别于出生后0、3、5、7天感染RRV，分为早期感染组(DOL 3感染)和晚期感染组(DOL 5后感染)。早期RRV感染可引起95%的仔猪出现症状，死亡率为80%。相比之下，晚期感染只有50%的小鼠出现症状，幼鼠100%存活。临床表现与肝外胆管树的组织学分析、细胞因子表达和病毒滴度有关。分离、培养和感染RRV的原代小鼠胆管细胞产生的感染病毒滴度高于DOL 2和DOL 9小鼠。DOL 2与DOL 9 RRV感染的原代胆管细胞相比，产生的干扰素α和β较少。与晚期感染野生型小鼠相比，在DOL 7时注射BALB/c干扰素α/β受体敲除(干扰素-αβR−/−)幼鼠的症状和死亡率增加(79%)和死亡率(46%)。总之，相对不成熟的胆管细胞因RRV复制而遭受的损伤程度与更严重的胆管病临床表现和更高的死亡率相关。胆管细胞产生的干扰素α似乎起到了调节作用。这些发现证实了RRV感染在小鼠BA中的时间依赖性，并开始确定成熟胆管细胞的病理生理作用。
Biliary atresia (BA) is a neonatal disease that results in obliteration of the biliary tree. The murine model of BA, which mirrors the human disease, is based upon infection of newborn mice with rhesus rotavirus (RRV), leading to an obstructive cholangiopathy. The purpose of this study was to characterize the temporal relationship between viral infection and the induction of this model. BALB/c mice were infected with RRV on day of life (DOL) 0, 3, 5, and 7. Groups were characterized as early-infection (infection by DOL 3) or late-infection (infection after DOL 5). Early RRV infection induced symptoms in 95% of pups with a mortality rate of 80%. In contrast, late infection caused symptoms in only 50% of mice, and 100% of pups survived. The clinical findings correlated with histological analysis of extrahepatic biliary trees, cytokine expression, and viral titers. Primary murine cholangiocytes isolated, cultured, and infected with RRV yielded higher titers of infectious virus in those harvested from DOL 2 versus DOL 9 mice. Less interferon alpha and beta was produced in DOL 2 versus DOL 9 RRV infected primary cholangiocytes. Injection of BALB/c interferon alpha/beta receptor knockout (IFN-αβR−/−) pups at DOL 7 showed increased symptoms (79%) and mortality (46%) when compared to late infected wild type mice. In conclusion, the degree of injury sustained by relatively immature cholangiocytes due to more robust RRV replication correlated with more severe clinical manifestations of cholangiopathy and higher mortality. Interferon alpha production by cholangiocytes appears to play a regulatory role. These findings confirm a temporal dependence of RRV infection in murine BA and begin to define a pathophysiologic role of the maturing cholangiocyte.
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影响因子：
2.4
作者：
Jafri, Mubeen;Donnelly, Bryan;Bondoc, Alex;Allen, Steven;Tiao, Greg
通讯作者：
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影响因子：
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作者：
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DOI：
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发表时间：
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