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

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...

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Autores principales: Castro, Victoria, Calvo, Gema, Ávila-Pérez, Ginés, Dreux, Marlène, Gastaminza, Pablo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6912735/
https://www.ncbi.nlm.nih.gov/pubmed/31752156
http://dx.doi.org/10.3390/cells8111456
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author Castro, Victoria
Calvo, Gema
Ávila-Pérez, Ginés
Dreux, Marlène
Gastaminza, Pablo
author_facet Castro, Victoria
Calvo, Gema
Ávila-Pérez, Ginés
Dreux, Marlène
Gastaminza, Pablo
author_sort Castro, Victoria
collection PubMed
description 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.
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spelling pubmed-69127352020-01-02 Differential Roles of Lipin1 and Lipin2 in the Hepatitis C Virus Replication Cycle Castro, Victoria Calvo, Gema Ávila-Pérez, Ginés Dreux, Marlène Gastaminza, Pablo Cells Article 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. MDPI 2019-11-18 /pmc/articles/PMC6912735/ /pubmed/31752156 http://dx.doi.org/10.3390/cells8111456 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Castro, Victoria
Calvo, Gema
Ávila-Pérez, Ginés
Dreux, Marlène
Gastaminza, Pablo
Differential Roles of Lipin1 and Lipin2 in the Hepatitis C Virus Replication Cycle
title Differential Roles of Lipin1 and Lipin2 in the Hepatitis C Virus Replication Cycle
title_full Differential Roles of Lipin1 and Lipin2 in the Hepatitis C Virus Replication Cycle
title_fullStr Differential Roles of Lipin1 and Lipin2 in the Hepatitis C Virus Replication Cycle
title_full_unstemmed Differential Roles of Lipin1 and Lipin2 in the Hepatitis C Virus Replication Cycle
title_short Differential Roles of Lipin1 and Lipin2 in the Hepatitis C Virus Replication Cycle
title_sort differential roles of lipin1 and lipin2 in the hepatitis c virus replication cycle
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6912735/
https://www.ncbi.nlm.nih.gov/pubmed/31752156
http://dx.doi.org/10.3390/cells8111456
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