Effect of rotavirus strain on the murine model of biliary atresia.
Biliary atresia is a devastating disorder of the newborn in which afflicted infants develop inflammation and fibrosis of the extrahepatic biliary tract, resulting in cirrhosis and end-stage liver disease. Infection with a virus is thought to be a contributing factor in the etiology of biliary atresia. In the murine model of biliary atresia, perinatal exposure to rhesus rotavirus (RRV) results in biliary epithelial cell infection causing bile duct obstruction. The purpose of this study was to determine if tropism for the biliary epithelial cell was unique to RRV. Newborn mice underwent intraperitoneal injection with five strains of rotavirus: RRV (simian), SA11-FM (simian/bovine), SA11-SM (simian), EDIM (murine), and Wa (human). RRV and SA11-FM caused clinical manifestations of bile duct obstruction and high mortality. SA11-SM caused clinical signs of hepatobiliary injury but the mortality was markedly reduced. EDIM and Wa caused no sign of hepatobiliary disease. The systemic and temporal distribution of viral protein and live virus varied according to the injected strain. Immunohistochemistry revealed that RRV and SA11-FM targeted the biliary epithelial cells. In contrast, SA11-SM was found in the liver but in not in the biliary epithelium. These results indicate that strain-specific characteristics dictate tropism for cells of hepatobiliary origin which in turn impact the ability to induce the murine model of biliary atresia.
Allen
Steven R
SR
Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, MLC 2923, Cincinnati, OH 45229, USA.
Jafri
Mubeen
M
Donnelly
Bryan
B
McNeal
Monica
M
Witte
David
D
Bezerra
Jorge
J
Ward
Richard
R
Tiao
Gregory M
GM
D000818:Animals; D000831:Animals, Newborn; D001652:Bile Ducts / Q000473:pathology / Q000821:virology; D001656:Biliary Atresia / Q000503:physiopathology / Q000821:virology*; D002460:Cell Line; D002779:Cholestasis / Q000473:pathology; D004847:Epithelial Cells / Q000821:virology; D005260:Female; D007150:Immunohistochemistry; D008099:Liver / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D012401:Rotavirus / Q000302:isolation & purification / Q000472:pathogenicity*; D012400:Rotavirus Infections / Q000821:virology*; D013045:Species Specificity; D014764:Viral Proteins / Q000378:metabolism
D014764:Viral Proteins