PRJNA559203
Temporal transcriptome and miRNome analysis reveal host responses to hepatitis C virus infection in Huh7 cells
Hepatitis C virus (HCV) is a leading etiology of liver-specific morbidity and mortality in humans. The HCV-host interplays during infection disturb cellular homeostasis and ultimately cause pathologic consequence including steatosis, cirrhosis, and hepatocellular carcinoma. Here we simultaneously investigated HCV-induced alterations of transcriptome and miRNome in Huh7 cells at 12 h, 36 h and 60 h after infection using by high-throughput RNA-seq. Number of the deregulated genes in the HCV-infected cells increases with infection time. The altered biological processes at 36 h are mainly associated with stress and inflammatory response, whereas the most enriched processes at 60 h are predominantly linked to lipid metabolism. Notably, the key genes participated in lipogenesis were down-regulated and the genes implicated in fatty acid beta-oxidation are up-regulated. Reduced expression of the key genes implicated in lipoprotein assembly and secretion points to decreased requirement and export of lipid, thereby leading to lipid accumulation in HCV-infected hepatocytes. The transcriptome also revealed expression fluctuation of the genes involved in host factors, innate immunity and transcription factors, which provide insights into host-directed mechanisms to control viral replication. miRNome presented a comprehensive expression profile of miRNAs in HCV-infected Huh7 cells. Decreased miR-122 and increased XRN1 at 60 h are expected to cooperatively decay excess HCV and attenuate its rampant replication, potentially contributing to viral persistence. The integrated analysis of mRNA and miRNA suggest deregulated miR-483, miR-1303, miR-1260a, miR-27a*, and miR-21* at 60 h directly regulate lipid metabolism. The de-repressed targets of miR-122 are not directly involved in lipid metabolism but amino acid transports. Our results will help to gain a comprehensive understanding of the molecular mechanisms implicated in HCV-induced pathogenesis.