Transcriptome and miRNome Analysis Provide New Insight Into Host Lipid Accumulation, Innate Immunity, and Viral...

Area of Science:

• Molecular virology
• Host-pathogen interactions
• Cellular biology

Background:

• Hepatitis C virus (HCV) infection disrupts cellular homeostasis, leading to pathological outcomes.
• Gene expression changes in HCV-infected cells are critical for understanding host responses.

Purpose of the Study:

• To investigate transcriptome and miRNome alterations in HCV-infected Huh7 cells.
• To systematically explore host responses to HCV infection over time (12, 36, and 60 hours).

Main Methods:

• Transcriptome and miRNA expression profiling (miRNome) of HCV-infected Huh7 cells.
• Time-course analysis at 12, 36, and 60 hours post-infection.
• Integrated analysis of transcriptomic and miRNomic data.

Main Results:

• Increased deregulation of genes with infection duration.
• Early changes (36h) linked to stress and inflammation; later changes (60h) dominated by lipid metabolism alterations.
• Downregulation of lipogenesis genes, upregulation of fatty acid beta-oxidation genes, and altered lipoprotein metabolism observed.
• Specific miRNAs (miR-483, miR-1303, miR-1260a, miR-27a*, miR-21*) identified as regulators of lipid metabolism at 60h.
• Decreased miR-122 at 60h indirectly impacts lipid metabolism and may influence viral replication and persistence.

Conclusions:

• HCV infection profoundly alters host gene and miRNA expression, particularly affecting lipid metabolism.
• Specific miRNAs play direct and indirect roles in regulating lipid metabolism during HCV infection.
• Understanding these molecular mechanisms is crucial for comprehending HCV pathogenesis and developing therapeutic strategies.