Here's and intersting article ...

[Guest guest]

Here's an interesting article that links a PSC-like disease to a

virus infection (murid herpesvirus-4) in a mouse model, where the

mice are defective for the gamma interferon receptor:

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Hepatology Research Volume 39 Issue 2, Pages 187 - 194 (2009)

Murid herpesvirus-4 induces chronic inflammation of intrahepatic bile

ducts in mice deficient in gamma-interferon signalling.

Babunilayam Gangadharan, 1 * Bernadette M Dutia, 1 M Rhind 2

and A Nash 1

1 Centre for Infectious Diseases, University of Edinburgh,

Edinburgh, and 2 Division of Veterinary Clinical Sciences, Royal

(Dick) School of Veterinary Studies, Midlothian, UK

Correspondence to Professor A. Nash, Centre for Infectious

Diseases, University of Edinburgh, Royal (Dick) School of Veterinary

Studies, Summerhall, Edinburgh, EH9 1QH, UK. Email:

Tony.Nash@...

* Present address: Neuropathogenesis Division, The Roslin

Institute, Edinburgh.

KEYWORDS

arginase • cholangitis • gamma interferon • gamma herpes virus

ABSTRACT

Aim: Infection of gamma interferon receptor defective mice with murid

herpesvirus-4 also known as murine gammaherpesvirus-68 results in

multi-organ fibrosis. In this paper we characterise the pathological

changes occurring in the liver in this model.

Methods: Standard immunohistochemistry and in situ hybridisation

techniques were used to identify the cellular changes and the

presence of virus at different times post infection.

Results: In liver sections from infected gamma interferon receptor

defective mice sampled on day 16 to at least day 120, 79% showed

proliferating intrahepatic bile ducts associated with a chronic

mononuclear cell inflammation. Only 8% of wild type mice showed

similar lesions. Coincident with the inflammatory response bile duct

epithelial cells were positive for arginase 1. Around day 50 post

infection onwards focal fibrotic lesions appeared in approximately

30% of gamma interferon receptor defective mice resulting in

destruction of intrahepatic bile ducts. In contrast to the chronic

persisting inflammatory response the presence of virus infected cells

were only observed between day 12–20 post-infection.

Conclusion: Infection of gamma interferon receptor defective mice

with a murine gammaherpesvirus initiates a chronic persisting

inflammatory response with a pathological profile similar to the

human fibrotic liver disorder Primary Sclerosing Cholangitis.

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Dave

(father of (23); PSC 07/03; UC 08/03)