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

Cholangiocyte expression of α2β1-integrin confers susceptibility to rotavirus-induced... Inoculation 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 α 2 β 1 . We hypothesized that cholangiocytes were susceptible to RRV infection because they express α 2 β 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 α 2 β 1 was present. Cholangiocytes were blocked with natural ligands, a monoclonal antibody, or small interfering RNA against the α 2 -subunit and were infected with RRV. The extrahepatic biliary tract of newborn mice was screened for the expression of the α 2 β 1 -integrin. Newborn mice were pretreated with a monoclonal antibody against the α 2 -subunit and were inoculated with RRV. RRV attached and replicated significantly better in cholangiocytes than in hepatocytes. Cholangiocytes, but not hepatocytes, expressed α 2 β 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-α 2 monoclonal antibody reduced the ability of RRV to cause biliary atresia in mice. Cell-surface expression of the α 2 β 1 -integrin plays a role in the mechanism that confers cholangiocyte susceptibility to RRV infection. rhesus rotavirus; bile ducts; cholangiopathy Address for reprint requests and other correspondence: G. M. Tiao, Cincinnati Children's Hospital Medical Center, MLC 2023, 3333 Burnet Ave, Cincinnati, OH 45229 (e-mail: Greg.Tiao@cchmc.org ) http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png AJP - Gastrointestinal and Liver Physiology The American Physiological Society

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

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Publisher
The American Physiological Society
Copyright
Copyright © 2011 the American Physiological Society
ISSN
0193-1857
eISSN
1522-1547
DOI
10.1152/ajpgi.00442.2007
pmid
18436621
Publisher site
See Article on Publisher Site

Abstract

Inoculation 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 α 2 β 1 . We hypothesized that cholangiocytes were susceptible to RRV infection because they express α 2 β 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 α 2 β 1 was present. Cholangiocytes were blocked with natural ligands, a monoclonal antibody, or small interfering RNA against the α 2 -subunit and were infected with RRV. The extrahepatic biliary tract of newborn mice was screened for the expression of the α 2 β 1 -integrin. Newborn mice were pretreated with a monoclonal antibody against the α 2 -subunit and were inoculated with RRV. RRV attached and replicated significantly better in cholangiocytes than in hepatocytes. Cholangiocytes, but not hepatocytes, expressed α 2 β 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-α 2 monoclonal antibody reduced the ability of RRV to cause biliary atresia in mice. Cell-surface expression of the α 2 β 1 -integrin plays a role in the mechanism that confers cholangiocyte susceptibility to RRV infection. rhesus rotavirus; bile ducts; cholangiopathy Address for reprint requests and other correspondence: G. M. Tiao, Cincinnati Children's Hospital Medical Center, MLC 2023, 3333 Burnet Ave, Cincinnati, OH 45229 (e-mail: Greg.Tiao@cchmc.org )

Journal

AJP - Gastrointestinal and Liver PhysiologyThe American Physiological Society

Published: Jul 1, 2008

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