title: Ethanol affects hepatitis C pathogenesis: humanized SCID Alb-uPA mouse model.
abstract: Alcohol consumption exacerbates the course of hepatitis C viral (HCV) infection, worsens outcomes and contributes to the development of chronic infection that exhibits low anti-viral treatment efficiency. The lack of suitable in vivo models makes HCV-ethanol studies very difficult. Here, we examine whether chimeric SCID Alb-uPA mice transplanted with human hepatocytes and infected with HCV develop worsening pathology when fed ethanol. After 5 weeks of feeding, such mice fed chow+water (control) or chow+20% ethanol in water (EtOH) diets mice developed oxidative stress, decreased proteasome activity and increased steatosis. Importantly, HCV(+) mice in the control group cleared HCV RNA after 5 weeks, while the infection persisted in EtOH-fed mice at the same or even higher levels compared with pre-feeding HCV RNA. We conclude that in chimeric SCID Alb-uPA mice, EtOH exposure causes the complex biochemical and histological changes typical for alcoholic liver injury. In addition, ethanol feeding delays the clearance of HCV RNA thereby generating persistent infection and promoting liver injury. Overall, this model is appropriate for conducting HCV-ethanol studies.
authors: Research Service, Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, NE, USA; Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68105, USA. Electronic address: nosna@unmc.edu.
authors: Natalia A
authors: NA
authors: Osna
authors: Research Service, Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, NE, USA; Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68105, USA.
authors: Kusum K
authors: KK
authors: Kharbanda
authors: Department of Surgery, University of Nebraska Medical Center, Omaha, NE 68105, USA.
authors: Yimin
authors: Y
authors: Sun
authors: Research Service, Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, NE, USA; Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68105, USA.
authors: Ronda L
authors: RL
authors: Simpson
authors: Research Service, Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, NE, USA; Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68105, USA.
authors: Larisa E
authors: LE
authors: Poluektova
authors: Research Service, Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, NE, USA; Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68105, USA.
authors: Murali
authors: M
authors: Ganesan
authors: Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68105, USA.
authors: James L
authors: JL
authors: Wisecarver
authors: Department of Surgery, University of Nebraska Medical Center, Omaha, NE 68105, USA.
authors: David F
authors: DF
authors: Mercer
mesh_terms: D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000473:pathology* / Q000503:physiopathology*; D004195:Disease Models, Animal; D000431:Ethanol; D006526:Hepatitis C / Q000139:chemically induced / Q000473:pathology* / Q000503:physiopathology*; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
chemical_list: D017392:Thiobarbituric Acid Reactive Substances; D000431:Ethanol
keywords: Alcohol; Hepatitis C virus; Oxidative stress; Proteasome activity; SCID Alb-uPA mice