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.

Original languageEnglish (US)
Pages (from-to)773-776
Number of pages4
JournalBiochemical and Biophysical Research Communications
Volume450
Issue number1
DOIs
StatePublished - Jul 18 2014

Fingerprint

Hepatitis C
Ethanol
Viral RNA
Liver
Oxidative stress
Water
Pathology
Proteasome Endopeptidase Complex
Nutrition
Infection
Alcohols
Wounds and Injuries
Virus Diseases
Alcohol Drinking
Hepatocytes
Oxidative Stress
Diet
Control Groups

Keywords

  • Alcohol
  • Hepatitis C virus
  • Oxidative stress
  • Proteasome activity
  • SCID Alb-uPA mice

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

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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.",
keywords = "Alcohol, Hepatitis C virus, Oxidative stress, Proteasome activity, SCID Alb-uPA mice",
author = "Osna, {Natalia A} and Kusum Kharbanda and Yimin Sun and Simpson, {Ronda L.} and Poluektova, {Larisa Y} and Murali Ganesan and Wisecarver, {James Lowell} and Mercer, {David F}",
year = "2014",
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AU - Osna, Natalia A

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AU - Sun, Yimin

AU - Simpson, Ronda L.

AU - Poluektova, Larisa Y

AU - Ganesan, Murali

AU - Wisecarver, James Lowell

AU - Mercer, David F

PY - 2014/7/18

Y1 - 2014/7/18

N2 - 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.

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