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

Mubeen Jafri, Bryan Donnelly, Steven Allen, Alex Bondoc, Monica McNeal, Paul D. Rennert, Paul H. Weinreb, Richard Ward, Greg Tiao

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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 α2β1. We hypothesized that cholangiocytes were susceptible to RRV infection because they express α2β1. 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 α2β1 was present. Cholangiocytes were blocked with natural ligands, a monoclonal antibody, or small interfering RNA against the α2-subunit and were infected with RRV. The extrahepatic biliary tract of newborn mice was screened for the expression of the α2β1-integrin. Newborn mice were pretreated with a monoclonal antibody against the α2-subunit and were inoculated with RRV. RRV attached and replicated significantly better in cholangiocytes than in hepatocytes. Cholangiocytes, but not hepatocytes, expressed α2β1 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-α2 monoclonal antibody reduced the ability of RRV to cause biliary atresia in mice. Cell-surface expression of the α2β1-integrin plays a role in the mechanism that confers cholangiocyte susceptibility to RRV infection.

Original languageEnglish (US)
Pages (from-to)G16-G26
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume295
Issue number1
DOIs
StatePublished - Jul 1 2008

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Biliary Atresia
Rotavirus
Integrins
Rotavirus Infections
Hepatocytes
Monoclonal Antibodies
Virus Attachment
Cell Line
Biliary Tract
Small Interfering RNA
Flow Cytometry
Epithelial Cells
Ligands
Infection

All Science Journal Classification (ASJC) codes

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)

Cite this

Jafri, Mubeen ; Donnelly, Bryan ; Allen, Steven ; Bondoc, Alex ; McNeal, Monica ; Rennert, Paul D. ; Weinreb, Paul H. ; Ward, Richard ; Tiao, Greg. / Cholangiocyte expression of α2β1-integrin confers susceptibility to rotavirus-induced experimental biliary atresia. In: American Journal of Physiology - Gastrointestinal and Liver Physiology. 2008 ; Vol. 295, No. 1. pp. G16-G26.
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Cholangiocyte expression of α2β1-integrin confers susceptibility to rotavirus-induced experimental biliary atresia. / Jafri, Mubeen; Donnelly, Bryan; Allen, Steven; Bondoc, Alex; McNeal, Monica; Rennert, Paul D.; Weinreb, Paul H.; Ward, Richard; Tiao, Greg.

In: American Journal of Physiology - Gastrointestinal and Liver Physiology, Vol. 295, No. 1, 01.07.2008, p. G16-G26.

Research output: Contribution to journalArticle

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AU - Jafri, Mubeen

AU - Donnelly, Bryan

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