Host phosphatidic acid phosphatase lipin1 is rate limiting for functional hepatitis C virus replicase complex formation

PLoS Pathogens
Lidia MingorancePablo Gastaminza

Abstract

Hepatitis C virus (HCV) infection constitutes a significant health burden worldwide, because it is a major etiologic agent of chronic liver disease, cirrhosis and hepatocellular carcinoma. HCV replication cycle is closely tied to lipid metabolism and infection by this virus causes profound changes in host lipid homeostasis. We focused our attention on a phosphatidate phosphate (PAP) enzyme family (the lipin family), which mediate the conversion of phosphatidate to diacylglycerol in the cytoplasm, playing a key role in triglyceride biosynthesis and in phospholipid homeostasis. Lipins may also translocate to the nucleus to act as transcriptional regulators of genes involved in lipid metabolism. The best-characterized member of this family is lipin1, which cooperates with lipin2 to maintain glycerophospholipid homeostasis in the liver. Lipin1-deficient cell lines were generated by RNAi to study the role of this protein in different steps of HCV replication cycle. Using surrogate models that recapitulate different aspects of HCV infection, we concluded that lipin1 is rate limiting for the generation of functional replicase complexes, in a step downstream primary translation that leads to early HCV RNA replication. Infection studies...Continue Reading

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Dec 8, 2019·Cells·Christina Whitten-BauerUrtzi Garaigorta
Oct 1, 2019·Annual Review of Virology·Ellen Ketter, Glenn Randall
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Aug 10, 2021·World Journal of Gastroenterology : WJG·Hui-Chun LiShih-Yen Lo

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Methods Mentioned

BETA
confocal microscopy
transfection
acetylation
sumoylation
PCR
electrophoresis
Assay
FCS
fluorescence microscopy
electron microscopy

Software Mentioned

LAS AF
Image J
ImageJ

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