Cellular Gene Expression during Hepatitis C Virus Replication as Revealed by Ribosome Profiling

Area of Science:

• Hepatology
• Virology
• Molecular Biology
• Cancer Research

Background:

• Hepatitis C virus (HCV) infects liver cells, potentially causing cirrhosis and liver cancer (HCC).
• Chronic HCV infection is linked to altered host gene expression and HCC development.
• HCV replication induces endoplasmic reticulum (ER) stress, but its genome-wide effects on host mRNA translation and transcription remain unclear.

Purpose of the Study:

• To investigate genome-wide changes in host mRNA translation and transcription during HCV replication.
• To understand how HCV infection impacts host gene expression at the transcriptomic and translatomic levels.

Main Methods:

• Utilized Ribosome Profiling (Riboseq) to analyze transcriptome and translatome.
• Studied the Huh-7.5 hepatocarcinoma cell line with established HCV replication for 6 days.

Main Results:

• Established HCV replication caused minimal global gene expression changes (approx. 30 genes).
• Upregulated genes were associated with ER stress and HCV replication, including some linked to HCC.
• Downregulation of mitochondrial respiratory chain genes was observed, with potential uORF-mediated translation control for specific mRNAs.

Conclusions:

• Lack of global gene expression changes suggests host adaptation to chronic HCV infection.
• Downregulation of mitochondrial genes indicates viral contribution to metabolic reprogramming (Warburg effect) in HCC cells.