LncRNA HULC facilitates efficient loading of HCV-core protein onto lipid droplets and subsequent virus-particle release.

Abstract

The cellular lipid pool plays a central role in hepatitis C virus (HCV) life cycle, from establishing infection to virus propagation. Here, we show that a liver abundant long noncoding RNA, highly upregulated in liver carcinoma (HULC), is upregulated during HCV infection and manipulates the lipid pool to favour virus life cycle. Interestingly, HULC was found to be crucial for the increase in number of lipid droplets in infected cells. This effect was attributed to the role of HULC in lipid biogenesis. Further, we demonstrated that HULC knockdown decreases the association of HCV-core protein with lipid droplets. This exhibited a direct consequence on the release of HCV particles. The role of HULC in HCV-particle release was further substantiated by additional knockdown and mutation experiments. Additionally, we found that increased level of HULC in HCV-infected cells was a result of Retinoid X Receptor Alpha (RXRA)-mediated transcription, which seemed to be aided by HCV-core protein. Taken together, the results identify a distinct role of long noncoding RNA HULC in lipid dynamics during HCV infection, which provides new insights into the complex process of HCV propagation and pathogenesis.