Reovirus type 3Infection in Biliary Atresia

本研究的目的是：1)用抗R3型呼肠孤病毒(R3)抗体对胆道闭锁(BA)婴儿开塞手术中获取的肝脏进行免疫组织化学；2)用逆转录聚合酶链式反应(RT-PCR)检测肝脏中R3的RNA；3)阐明接种R3的新生小鼠胆道梗阻的病理生理机制。我们的研究结果如下：1)25个BA肝中有24个能与抗R3(Abney株：A)多克隆抗体反应，但不能与抗R3(德林株：D)单克隆抗体反应，这可能是由于这些较弱的染色活性所致。2)3例BA肝组织和2例非肝病对照组肝组织均检测到D基因M1片段。3)接种R3-A的新生小鼠肝脏和胆总管表现出与人类胆道闭锁相似的组织学特征，表现为胆管上皮细胞变性，周围有单核细胞浸润，R3-A相关抗原阳性。最近的一份报告表明，R3-A的一部分S1片段可能在决定该病毒对导管上皮的趋向性中发挥作用。因此，我们认为应该尝试用逆转录-聚合酶链式反应来检测这一部分。虽然在本研究中我们不能得出结论R3导致BA，但我们的结果强烈提示R3-A感染可能触发BA硬化性胆管炎的闭塞过程。

The aim of the present study was 1) to perform immunohistochemistry of livers obtained during Kasai operation for infants with biliary atresia (BA) using anti-reovirus type 3 (R3), 2) to detect the RNAs of R3 from those livers with reverse transcriptase-polymerase chain reaction and 3) to elucidate pathophysiology of biliary obstruction in the neonatal mice inoculated with R3. We summarise our results as follows ; 1) 24 of 25 livers of BA reacted with anti-R3 (Abney strain : A) polyclonal antibodies, but none with anti-R3 (Dearing strain : D) monoclonal ones probably because of these weaker staining activities. 2) M1 segment of D was detected in both 3livers of BA and 2 with non-liver disease controls. 3) The liver and choledochus of neonatal mice inoculated with R3-A developed histologically similar features with human biliary atresia such as degeneration of ductular epithelia, surrounded with mononuclear infiltration, and positive R3-A associated antigens. A recent report suggests that a part of S1 segment of R3-A may play a role in determining the tropism of this virus for ductular epithelium. Therefore we believe we should try to detect this part with reverse transcription-polymerase chain reaction. Although we could not conclude that R3 causes BA in the present study, our results strongly suggest that R3-A infection may trigger the obliterative process of sclerosing cholangitis in BA.