Differential Roles of Lipin1 and Lipin2 in the Hepatitis C Virus Replication Cycle

© The Author(s).
Although their origin, nature and structure are not identical, a common feature of positive-strand RNA viruses is their ability to subvert host lipids and intracellular membranes to generate replication and assembly complexes. Recently, lipin1, a cellular enzyme that converts phosphatidic acid into diacylglycerol, has been implicated in the formation of the membranous web that hosts hepatitis C virus (HCV) replicase. In the liver, lipin1 cooperates with lipin2 to maintain glycerolipid homeostasis. We extended our previous study of the lipin family on HCV infection, by determining the impact of the lipin2 silencing on viral replication. Our data reveal that lipin2 silencing interferes with HCV virion secretion at late stages of the infection, without significantly affecting viral replication or assembly. Moreover, uninfected lipin2-, but not lipin1-deficient cells display alterations in mitochondrial and Golgi apparatus morphology, suggesting that lipin2 contributes to the maintenance of the overall organelle architecture. Finally, our data suggest a broader function of lipin2 for replication of HCV and other RNA viruses, in contrast with the specific impact of lipin1 silencing on HCV replication. Overall, this study reveals distinctive functions of lipin1 and lipin2 in cells of hepatic origin, a context in which they are often considered functionally redundant.
This study was supported by grants SAF2014-52400-R and SAF2017-87846-R from Ministry of Science, Research and Universities from the Spanish Government (MCIU/AEI/FEDER, UE) and the International Program “Make Our Planet Great Again” (mopga-short-0000000612) from the French Government and European Union’s Horizon 2020 Research and innovation program under “ZIKALLIANCE” (Grant Agreement no. 734548) to MD. VC is supported by predoctoral fellowship BES-2015-074920 from MCIU/AEI/FEDER, UE.