Reovirus type 3Infection in Biliary Atresia

本研究的目的是：1)利用抗呼肠孤病毒3型（R3）对胆道闭锁（BA）患儿行Kasai手术后获得的肝脏进行免疫组化，2)检测逆转录-聚合酶链反应肝脏中R3的rna， 3)阐明接种R3的新生小鼠胆道梗阻的病理生理。我们将结果总结如下：1) 25只BA肝脏中有24只与抗r3 （Abney株：A）多克隆抗体反应，而与抗r3 （Dearing株：D）单克隆抗体反应均为阴性，可能是由于这些单克隆抗体的染色活性较弱。2) 3例BA和2例非肝病对照者肝脏均检测到D的M1段。3)接种R3-A的新生小鼠肝脏和胆道出现了与人胆道闭锁相似的组织学特征，如导管上皮变性，单核浸润，R3-A相关抗原阳性。最近的一份报告表明，R3-A的一部分S1段可能在决定该病毒对导管上皮的趋向性中起作用。因此，我们认为应该尝试用逆转录-聚合酶链反应检测这部分。虽然我们在本研究中不能得出R3引起BA的结论，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.