Impact of combination antiretroviral therapy in the NOD.c3c4 mouse model of autoimmune biliary disease

Autor: Don Graham, Aldo J. Montano-Loza, Andrew Mason, Banu Sis, Chelsea McDougall, Safwat Girgis, Min Chen, Shawn T. Wasilenko, Guangzhi Zhang, David Sharon
Jazyk: angličtina
Rok vydání: 2014
Předmět:
Time Factors
Cholangitis
Molecular Sequence Data
mouse mammary tumour virus
Biology
Emtricitabine
NOD.c3c4
Lopinavir
Biliary disease
Liver disease
Zidovudine
Primary biliary cirrhosis
Mice
Inbred NOD
Cholestasis and Autoimmune Liver Disease
medicine
Animals
Protease Inhibitors
Amino Acid Sequence
Granulomatous cholangitis
Ritonavir
Hepatology
Liver Cirrhosis
Biliary
Emtricitabine
Tenofovir Disoproxil Fumarate Drug Combination
Viral Load
medicine.disease
3. Good health
primary biliary cirrhosis
Disease Models
Animal
Drug Combinations
Tumor Virus Infections
autoimmune biliary disease
Anti-Retroviral Agents
Mammary Tumor Virus
Mouse
Lamivudine
Immunology
combination antiretroviral therapy
RNA
Viral
Reverse Transcriptase Inhibitors
Drug Therapy
Combination
Female
Biomarkers
medicine.drug
Retroviridae Infections
Zdroj: Liver International
ISSN: 1478-3231
1478-3223
Popis: Background & Aims The NOD.c3c4 mouse model develops autoimmune biliary disease characterized by spontaneous granulomatous cholangitis, antimitochondrial antibodies and liver failure. This model for primary biliary cirrhosis (PBC) has evidence of biliary infection with mouse mammary tumour virus (MMTV), suggesting that the virus may have a role in cholangitis development and progression of liver disease in this mouse model. We tested the hypothesis that MMTV infection is associated with cholangitis in the NOD.c3c4 mouse model by investigating whether antiretroviral therapy impacts on viral levels and liver disease. Methods NOD.c3c4 mice were treated with combination antiretroviral therapy. Response to treatment was studied by measuring MMTV RNA in the liver, liver enzyme levels in serum and liver histology using a modified Ishak score. Results Combination therapy with the reverse transcriptase inhibitors, tenofovir and emtricitabine, resulted in a significant reduction in serum liver enzyme levels, attenuation of cholangitis and decreased MMTV levels in the livers of NOD.c3c4 mice. Furthermore, treatment with the retroviral protease inhibitors, lopinavir and ritonavir, in addition to the reverse transcriptase inhibitors, resulted in further decrease in MMTV levels and attenuation of liver disease in this model. Conclusions The attenuation of cholangitis with regimens containing the reverse transcriptase inhibitors, tenofovir and emtricitabine, and the protease inhibitors, lopinavir and ritonavir, suggests that retroviral infection may play a role in the development of cholangitis in this model.
Databáze: OpenAIRE
Externí odkaz: