Sharma Geetika, Tripathi Sachin Kumar, Das Saumitra
Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, India.
National Institute of Biomedical Genomics, Kalyani, India.
Cell Microbiol. 2019 Oct;21(10):e13086. doi: 10.1111/cmi.13086. Epub 2019 Jul 22.
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.
细胞脂质池在丙型肝炎病毒（HCV）生命周期中起着核心作用，从建立感染到病毒传播。在此，我们表明一种在肝癌中高度上调的肝脏丰富长链非编码RNA（HULC）在HCV感染期间上调，并操纵脂质池以促进病毒生命周期。有趣的是，发现HULC对于感染细胞中脂滴数量的增加至关重要。这种作用归因于HULC在脂质生物合成中的作用。此外，我们证明HULC敲低会降低HCV核心蛋白与脂滴的结合。这对HCV颗粒的释放产生了直接影响。通过额外的敲低和突变实验进一步证实了HULC在HCV颗粒释放中的作用。此外，我们发现HCV感染细胞中HULC水平的升高是视黄酸X受体α（RXRA）介导的转录的结果，这似乎得到了HCV核心蛋白的辅助。综上所述，这些结果确定了长链非编码RNA HULC在HCV感染期间脂质动态中的独特作用，这为HCV传播和发病机制的复杂过程提供了新的见解。
