How Rhesus Rotavirus Causes Biliary Atresia in Mice
Author Information
Author(s): Temple Haley, Donnelly Bryan, Mohanty Sujit K., Mowery Sarah, Poling Holly M., Pasula Rajamouli, Hartman Stephen, Singh Akaljot, Mourya Reena, Bondoc Alexander, Meller Jaroslaw, Jegga Anil G., Oyama Kei, McNeal Monica, Spearman Paul, Tiao Greg
Primary Institution: Cincinnati Children’s Hospital Medical Center
Hypothesis
Does the binding of Rhesus rotavirus to heat shock cognate 70 protein alter its method of endocytosis and induce biliary atresia in a murine model?
Conclusion
The study found that Rhesus rotavirus alters its endocytosis method through binding to Hsc70, leading to an inflammatory response that may cause biliary obstruction.
Supporting Evidence
- Rhesus rotavirus infection in newborn mice leads to symptoms similar to human biliary atresia.
- Blocking specific endocytosis pathways reduced viral infectivity.
- High levels of cytokines CXCL9 and CXCL10 were released following infection.
- TLR3 signaling was activated in cholangiocytes after rotavirus infection.
- Alteration of the 'SRL' peptide affected the virus's ability to induce biliary atresia.
- TLR3 knockout mice showed reduced bile duct obstruction compared to wild-type mice.
- Human patients with biliary atresia had elevated levels of CXCL10.
Takeaway
Rhesus rotavirus can change how it enters cells, which can lead to serious liver problems in baby mice, similar to a disease called biliary atresia in humans.
Methodology
The study involved infecting newborn mice with Rhesus rotavirus and analyzing the effects on cholangiocytes and cytokine release.
Potential Biases
Potential bias in interpreting results due to reliance on a single animal model.
Limitations
The study primarily used a murine model, which may not fully replicate human disease mechanisms.
Participant Demographics
Newborn mice were used in the study.
Statistical Information
P-Value
p<0.05
Statistical Significance
p<0.05
Digital Object Identifier (DOI)
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