Efficient conditional transgene expression in hepatitis C virus cDNA transgenic mice mediated by the Cre/loxP system

Area of Science:

• Virology
• Immunology
• Genetics

Background:

• Conditional gene expression is crucial for studying gene function.
• Hepatitis C virus (HCV) infection pathogenesis requires further investigation.
• Developing animal models is essential for studying viral diseases.

Purpose of the Study:

• To create an efficient conditional transgenic mouse model for hepatitis C virus (HCV) cDNA activation.
• To investigate the role of host immune response in HCV infection pathogenesis.

Main Methods:

• Utilized the Cre/loxP system for conditional transgene activation of HCV cDNA in mice.
• Administered adenovirus expressing Cre DNA recombinase to induce transgene expression in the liver.
• Analyzed viral protein expression, liver enzyme levels, and immune responses (antibody and cellular).
• Employed CD4 and CD8 positive cell depletion assays to assess immune cell roles.

Main Results:

• Achieved efficient recombination and expression of HCV core, E1, and E2 proteins in mouse liver hepatocytes.
• Observed increased serum core protein and alanine aminotransferase levels post-transgene activation.
• Detected anti-HCV antibody response and identified a critical role for CD4 and CD8 positive T-cells in controlling liver pathology and enzyme level increases.

Conclusions:

• HCV proteins are not directly cytopathic; the host immune response is the primary driver of liver damage in HCV infection.
• This HCV cDNA transgenic mouse model is a valuable tool for studying HCV immune responses and pathogenesis.