Author summary

Hepatitis C virus (HCV) infection is an important biomedical problem worldwide because it causes severe liver disease and cancer. Although immunological events are major players in HCV pathogenesis, interference with host cell metabolism contribute to HCV-associated pathologies. HCV utilizes resources of the cellular lipid metabolism to strongly modify subcellular compartments, using them as platforms for replication and infectious particle assembly. In particular, HCV induces the formation of a “membranous web” that hosts the viral machinery dedicated to the production of new copies of the viral genome. This lipid-rich structure provides an optimized platform for viral genome replication and hides new viral genomes from host´s antiviral surveillance. In this study, we have identified a cellular protein, lipin1, involved in the production of a subset of cellular lipids, as a rate-limiting factor for HCV infection. Our results indicate that the enzymatic activity of lipin1 is required to build the membranous compartment dedicated to viral genome replication. Lipin1 is probably contributing to the formation of the viral replication machinery by locally providing certain lipids required for an optimal membranous environment. Based on these results, interfering with lipin1 capacity to modify lipids may therefore constitute a potential strategy to limit HCV infection.

• Lidia Mingorance, Victoria Castro , Ginés Ávila-Pérez , Gema Calvo, María Josefa Rodriguez, José L. Carrascosa, Sofía Pérez-del-Pulgar, Xavier Forns, Pablo Gastaminza. Host phosphatidic acid phosphatase lipin1 is rate limiting for functional hepatitis C virus replicase complex formation. PLoS Pathog. 2018 Sep 18;14(9):e1007284. doi: 10.1371/journal.ppat.1007284.