HCV Induces Oxidative and ER Stress, and Sensitizes Infected Cells to Apoptosis in SCID/Alb-uPA Mice
2009

HCV Induces Stress and Cell Death in Infected Mice

Sample size: 3 publication 10 minutes Evidence: moderate

Author Information

Author(s): Joyce Michael A., Walters Kathie-Anne, Lamb Sue-Ellen, Yeh Mathew M., Zhu Lin-Fu, Kneteman Norman, Doyle Jason S., Katze Michael G., Tyrrell D. Lorne

Primary Institution: University of Alberta

Hypothesis

HCV infection leads to hepatocyte damage and apoptosis through the induction of oxidative and endoplasmic reticulum stress.

Conclusion

HCV infection contributes to liver cell damage and apoptosis by inducing stress while inhibiting protective anti-apoptotic mechanisms.

Supporting Evidence

  • HCV infection led to increased apoptosis in liver cells.
  • Oxidative stress and ER stress were identified as key factors in cell death.
  • Gene expression profiling showed activation of innate antiviral signaling pathways.
  • Increased levels of pro-apoptotic BAX were observed in infected cells.
  • Anti-apoptotic factors like NF-κB and BCL-xL were decreased in HCV-infected cells.
  • Histological analysis revealed signs of hepatocyte damage and inflammation.
  • FAS expression was elevated in infected cells, correlating with apoptosis.
  • Chimeric mice model effectively mimicked human HCV infection responses.

Takeaway

Hepatitis C virus can make liver cells sick and die by causing stress inside the cells, even without the immune system being involved.

Methodology

The study used chimeric SCID/Alb-uPA mice infected with HCV to analyze gene expression and apoptosis in liver cells.

Potential Biases

Potential bias in interpreting results due to the use of a specific mouse model that may not capture all human disease complexities.

Limitations

The study is limited to a mouse model and may not fully represent human responses to HCV infection.

Participant Demographics

Chimeric SCID/Alb-uPA mice with human hepatocytes.

Statistical Information

P-Value

≤0.05

Statistical Significance

p<0.05

Digital Object Identifier (DOI)

10.1371/journal.ppat.1000291

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