Analysis of Hepatitis C Virus Particle Heterogeneity in Immunodeficient Human Liver Chimeric fah-/- MiceSummary
| Autor: | Sonia Bergaya, Michiel C. Mommersteeg, Margaret A. Scull, Charles M. Rice, Jing W. Xiao, Corrine Quirk, Edward A. Fisher, Koen Vercauteren, Ype P. de Jong, Arjun Menon, Ursula Andreo |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Alb-uPA Albumin-urokinase plasminogen activator LVP lipoviroparticle Hepatitis C virus medicine.medical_treatment HDL high-density lipoprotein PBS phosphate-buffered saline Human Liver Chimeric Mice Liver transplantation Biology medicine.disease_cause 03 medical and health sciences chemistry.chemical_compound VLDL very low density lipoprotein 0302 clinical medicine HCVcc cell culture–derived hepatitis C virus SCID severe combined immunodeficiency disease medicine Secretion lcsh:RC799-869 Lipoprotein apo apolipoprotein Original Research Infectivity Mouse Model Hepatology Cholesterol FPLC fast-performance liquid chromatography NRG nod rag γ Gastroenterology FNRG absence of fumaryl acetoacetate hydrolase on a immunodeficient NOD Rag gamma IL2 deficient mouse background CETP cholesterol ester transfer protein Iodixanol Virology NTBC nitisinone 3. Good health FAH fumaryl acetoacetate hydrolase 030104 developmental biology chemistry HCV hepatitis C virus HCV Immunology 030211 gastroenterology & hepatology lcsh:Diseases of the digestive system. Gastroenterology Plasminogen activator medicine.drug |
| Zdroj: | Cellular and Molecular Gastroenterology and Hepatology, Vol 4, Iss 3, Pp 405-417 (2017) Cellular and Molecular Gastroenterology and Hepatology |
| Popis: | Background & Aims Hepatitis C virus (HCV) is a leading cause of chronic liver diseases and the most common indication for liver transplantation in the United States. HCV particles in the blood of infected patients are characterized by heterogeneous buoyant densities, likely owing to HCV association with lipoproteins. However, clinical isolates are not infectious in vitro and the relative infectivity of the particles with respect to their buoyant density therefore cannot be determined, pointing to the need for better in vivo model systems. Methods To analyze the evolution of the buoyant density of in vivo–derived infectious HCV particles over time, we infected immunodeficient human liver chimeric fumaryl acetoacetate hydrolase-/- mice with J6/JFH1 and performed ultracentrifugation of infectious mouse sera on isopicnic iodixanol gradients. We also evaluated the impact of a high sucrose diet, which has been shown to increase very-low-density lipoprotein secretion by the liver in rodents, on lipoprotein and HCV particle characteristics. Results Similar to the severe combined immunodeficiency disease/Albumin-urokinase plasminogen activator human liver chimeric mouse model, density fractionation of infectious mouse serum showed higher infectivity in the low-density fractions early after infection. However, over the course of the infection, viral particle heterogeneity increased and the overall in vitro infectivity diminished without loss of the human liver graft over time. In mice provided with a sucrose-rich diet we observed a minor shift in HCV infectivity toward lower density that correlated with a redistribution of triglycerides and cholesterol among lipoproteins. Conclusions Our work indicates that the heterogeneity in buoyant density of infectious HCV particles evolves over the course of infection and can be influenced by diet. Graphical abstract |
| Databáze: | OpenAIRE |
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