Role of reovirus type 3 in persistent infantile cholestasis

Glaser, Joy H.; Balistreri, William F.; Morecki, Rachel

doi:10.1016/s0022-3476(84)80076-1

Cited by 100 publications

(49 citation statements)

References 5 publications

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“…Interest in reovirus developed after the observation that infection in weanling mice caused extrahepatic bile duct cyst formation and intrahepatic bile duct pathologic features similar to those of BA (12). Serologic studies initially suggested an increased rate of infection with reovirus in infants with BA and neonatal hepatitis (13,14), however, subsequent studies could not confirm these findings (15,16).…”

Section: Viral and Other Infectious Agentsmentioning

confidence: 99%

Unraveling the Pathogenesis and Etiology of Biliary Atresia

2005

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Section: Viral and Other Infectious Agentsmentioning

confidence: 99%

Unraveling the Pathogenesis and Etiology of Biliary Atresia

2005

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“…It is the most common indication for pediatric liver transplantation (24). Because pathogenic viruses have been found in the livers of children afflicted with biliary atresia (10,12,18,26,29), a proposed etiology for biliary atresia is perinatal infection by a virus triggering inflammatory destruction of the biliary epithelium (3,23,32). A murine model of biliary atresia (30) supports a viral pathogenesis where newborn mice infected with rhesus rotavirus (RRV) develop inflammation within the portal tract (31) and extrahepatic bile duct obstruction (9, 27).…”

mentioning

confidence: 99%

Cholangiocyte expression of α₂β₁-integrin confers susceptibility to rotavirus-induced experimental biliary atresia

Jafri¹,

Donnelly²,

Allen³

et al. 2008

American Journal of Physiology-Gastrointestinal and Liver Physi

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lation of BALB/c mice with rhesus rotavirus (RRV) in the newborn period results in biliary epithelial cell (cholangiocyte) infection and the murine model of biliary atresia. Rotavirus infection of a cell requires attachment, which is governed in part by cell-surface expression of integrins such as ␣2␤1. We hypothesized that cholangiocytes were susceptible to RRV infection because they express ␣2␤1. RRV attachment and replication was measured in cell lines derived from cholangiocytes and hepatocytes. Flow cytometry was performed on these cell lines to determine whether ␣2␤1 was present. Cholangiocytes were blocked with natural ligands, a monoclonal antibody, or small interfering RNA against the ␣2-subunit and were infected with RRV. The extrahepatic biliary tract of newborn mice was screened for the expression of the ␣2␤1-integrin. Newborn mice were pretreated with a monoclonal antibody against the ␣2-subunit and were inoculated with RRV. RRV attached and replicated significantly better in cholangiocytes than in hepatocytes. Cholangiocytes, but not hepatocytes, expressed ␣2␤1 in vitro and in vivo. Blocking assays led to a significant reduction in attachment and yield of virus in RRV-infected cholangiocytes. Pretreatment of newborn pups with an anti-␣2 monoclonal antibody reduced the ability of RRV to cause biliary atresia in mice. Cell-surface expression of the ␣2␤1-integrin plays a role in the mechanism that confers cholangiocyte susceptibility to RRV infection. rhesus rotavirus; bile ducts; cholangiopathy BILIARY ATRESIA (BA) is a unique disease of infancy in which affected children develop fibroinflammatory obliteration of the biliary tract. It is the most common indication for pediatric liver transplantation (24). Because pathogenic viruses have been found in the livers of children afflicted with biliary atresia (10,12,18,26,29), a proposed etiology for biliary atresia is perinatal infection by a virus triggering inflammatory destruction of the biliary epithelium (3,23,32). A murine model of biliary atresia (30) supports a viral pathogenesis where newborn mice infected with rhesus rotavirus (RRV) develop inflammation within the portal tract (31) and extrahepatic bile duct obstruction (9, 27).Recently, it has been shown that in the murine model of biliary atresia, RRV targeted the biliary epithelial cell (cholangiocyte) for infection (1, 31). To determine the basis for cholangiocyte susceptibility to RRV, an in vitro model of RRV infection of the two dominant cell types found within the liver (cholangiocytes and hepatocytes) was established. Consistent with the in vivo findings, RRV was better able to replicate in cholangiocytes than hepatocytes. Because the ability of rotavirus to infect cells appears to be regulated by cell-surface expression of the integrins ␣ 2 ␤ 1 , ␣ 4 ␤ 1 , ␣ v ␤ 3 , and ␣ x ␤ 2 , which serve as viral receptors (8,13,14,16,21), the cholangiocyte was surveyed for integrin expression and found to uniquely express the ␣ 2 ␤ 1 -integrin when compared with hepatocytes. Based on this informat...

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“…Two types of evidence support a viral role in the pathogenesis of biliary atresia. The first type is patient-based studies in which viruses, including reovirus (11,19,20), cytomegalovirus (7,9), human papillomavirus (8), Epstein-Barr virus (10), and rotavirus (27), were found in the livers of infants with biliary atresia. The second type of evidence is the murine model of inflammatory cholangiopathy in which newborn mice injected with rhesus rotavirus (RRV) develop extrahepatic biliary obstruction and death (28).…”

mentioning

confidence: 99%

Effect of Rotavirus Strain on the Murine Model of Biliary Atresia

Allen¹,

Jafri²,

Donnelly³

et al. 2007

J Virol

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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.

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Role of reovirus type 3 in persistent infantile cholestasis

Cited by 100 publications

References 5 publications

Unraveling the Pathogenesis and Etiology of Biliary Atresia

Unraveling the Pathogenesis and Etiology of Biliary Atresia

Cholangiocyte expression of α₂β₁-integrin confers susceptibility to rotavirus-induced experimental biliary atresia

Effect of Rotavirus Strain on the Murine Model of Biliary Atresia

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Role of reovirus type 3 in persistent infantile cholestasis

Cited by 100 publications

References 5 publications

Unraveling the Pathogenesis and Etiology of Biliary Atresia

Unraveling the Pathogenesis and Etiology of Biliary Atresia

Cholangiocyte expression of α2β1-integrin confers susceptibility to rotavirus-induced experimental biliary atresia

Effect of Rotavirus Strain on the Murine Model of Biliary Atresia

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Cholangiocyte expression of α₂β₁-integrin confers susceptibility to rotavirus-induced experimental biliary atresia