The Rhesus Rotavirus Gene Encoding VP4 Is a Major Determinant in the Pathogenesis of Biliary Atresia in Newborn Mice

Rotavirus entry into a cell is a complex multistep process in which different domains of the rotavirus surface proteins interact with different cell surface molecules, which act as attachment and entry receptors. These recently described molecules include several integrins and a heat shock protein, which have been found to be associated with cell membrane lipid microdomains. The requirement during viral entry for several cell molecules, which might be required to be present and organized in a precise fashion, could explain the selective cell and tissue tropism of these viruses. This review focuses on recent data describing the virus-receptor interactions, the role of lipid microdomains in rotavirus infection and the mechanism of rotavirus cell entry.

The purpose of this retrospective study was to examine liver tissue from patients with cholestatic disease for the presence of group C rotavirus RNA. The reverse transcriptase-polymerase chain reaction (PCR) for genes 5 and 6 was used, and the PCR products were subjected to liquid hybridization with a 32P-labeled probe. A second amplification with nested primers was also used. Samples from 32 subjects (20 with biliary atresia or choledochal cyst and 12 controls) were tested. Ten of 20 biliary atresia patients were positive for group C rotavirus RNA; no controls were positive (P 1 sample that was positive. These data suggest a possible relationship between group C rotavirus and extrahepatic biliary atresia in the 10 patients in whom virus RNA was detected.

Extrahepatic biliary atresia (EHBA) and choledochal cysts (CDC) are important causes of obstructive jaundice in pediatric patients. Viruses in general, and reoviruses in particular, have long been considered as possible etiologic agents responsible for inciting the inflammatory process that leads to these infantile obstructive cholangiopathies. In an effort to determine whether reovirus infection is associated with these disorders, we used a sensitive and specific reverse-transcriptase polymerase chain reaction (RT-PCR) technique designed to amplify a portion of the reovirus L1 gene segment from extracts of liver and/or biliary tissues. These tissues were obtained at the time of liver biopsy or surgical procedures from 23 patients with EHBA, 9 patients with CDC, and 33 patients with other hepatobiliary diseases. Hepatic and biliary tissues obtained at autopsy from 17 patients who died without known liver or biliary disease were also analyzed. Reovirus RNA was detected in hepatic and/or biliary tissues from 55% of patients with EHBA and 78% of patients with CDC. Reovirus RNA was found also in extracts of hepatic and/or biliary tissue from 21% of patients with other hepatobiliary diseases and in 12% of autopsy cases. The prevalence of reovirus RNA in tissues from patients with EHBA and CDC was significantly greater than that in patients with other hepatobiliary diseases (chi2 P = .012 EHBA vs. OTHER, P = .001 CDC vs. OTHER), or AUTOPSY cases (chi2 P = .006 EHBA vs. AUTOPSY, P < .001 CDC vs. AUTOPSY).