Inhibition of long noncoding RNA Linc-Pint by hepatitis C virus in infected hepatocytes enhances lipogenesis.

BACKGROUND AND AIMS Hepatitis C virus (HCV) often causes chronic infection in liver, cirrhosis, and in some instances, hepatocellular carcinoma (HCC). HCV encodes several factors those impair host genes for establishment of chronic infection. The long non-coding RNAs (lncRNAs) display diverse effects on biological regulations. However, their role in virus replication and underlying diseases are poorly understood. In this study, we have shown that HCV exploits lncRNA Linc-Pint in hepatocytes for enhancement of lipogenesis. APPROACH AND RESULTS We identified a lncRNA, Linc-Pint, which is significantly downregulated in HCV replicating hepatocytes and infected patient liver specimens. Using RNA-pull down-proteomics, we identified serine/arginine protein specific kinase 2 (SRPK2) as an interacting partner of Linc-Pint. Subsequent study demonstrated that overexpression of Linc-Pint inhibits the expression of lipogenesis related genes, such as FASN and ACLY. We also observed that Linc-Pint significantly inhibits HCV replication. Further, HCV mediated enhanced lipogenesis can be controlled by exogenous Linc-Pint expression. Together our results suggested that HCV mediated downregulation of Linc-Pint enhances lipogenesis favouring virus replication and liver disease progression. CONCLUSIONS We have shown that SRPK2 is a direct target of Linc-Pint and depletion of SRPK2 inhibits lipogenesis. Our study contributes to the mechanistic understanding of the previously unexplored role of Linc-Pint in HCV associated liver pathogenesis.