Phospholipase D activity is elevated in hepatitis C virus core protein-transformed NIH3T3 mouse fibroblast cells

Kim, Joonmo; Choi, Bok Hee; Jang, Kyung Lib; Min, Do Sik

doi:10.1038/emm.2004.57

Cited by 11 publications

(9 citation statements)

References 32 publications

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“…Since the actin cytoskeleton (13) and signaling elements associated with Arf1 have been implicated in HCV pathogenesis (1,10,33,68,72,73), it is entirely conceivable that a reduction in Arf1 expression (by siRNA) would result in the collapse of Arf1-dependent signaling networks that play a role in HCV RNA replication and infectious virus biogenesis.…”

Section: Discussionmentioning

confidence: 99%

Role for ADP Ribosylation Factor 1 in the Regulation of Hepatitis C Virus Replication

Matto

Sklan

David

et al. 2011

J Virol

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We hypothesized that ADP-ribosylation factor 1 (Arf1) plays an important role in the biogenesis and maintenance of infectious hepatitis C virus (HCV). Huh7.5 cells, in which HCV replicates and produces infectious viral particles, were exposed to brefeldin A or golgicide A, pharmacological inhibitors of Arf1 activation. Treatment with these agents caused a reduction in viral RNA levels, the accumulation of infectious particles within the cells, and a reduction in the levels of these particles in the extracellular medium. Fluorescence analyses showed that the viral nonstructural (NS) proteins NS5A and NS3, but not the viral structural protein core, shifted their localization from speckle-like structures in untreated cells to the rims of lipid droplets (LDs) in treated cells. Using pulldown assays, we showed that ectopic overexpression of NS5A in Huh7 cells reduces the levels of GTP-Arf1. Downregulation of Arf1 expression by small interfering RNA (siRNA) decreased both the levels of HCV RNA and the production of infectious viral particles and altered the localization of NS5A to the peripheries of LDs. Together, our data provide novel insights into the role of Arf1 in the regulation of viral RNA replication and the production of infectious HCV.

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Section: Discussionmentioning

confidence: 99%

Role for ADP Ribosylation Factor 1 in the Regulation of Hepatitis C Virus Replication

Matto

Sklan

David

et al. 2011

J Virol

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“…Interestingly, PLD activity is also involved in virus-induced carcinoma. Hepatitis C virus core protein transforms NIH3T3 cells in a PLD-dependent fashion (Kim et al, 2004). …”

Section: Role Of Phospholipase D In Cancermentioning

confidence: 99%

Phosphatidic acid, phospholipase D and tumorigenesis

Gómez‐Cambronero

2014

Advances in Biological Regulation

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Phospholipase D (PLD) is a membrane protein with a double role: maintenance of the structural integrity of cellular or intracellular membranes and involvement in cell signaling through the product of the catalytic reaction, PA, and through protein–protein interaction with a variety of partners. Cross-talk during PLD signaling occurs with other cancer regulators (Ras, PDGF, TGF and kinases). Elevation of either PLD1 or PLD2 (the two mammalian isoforms of PLD) is able to transform fibroblasts and contribute to cancer progression. Elevated total PLD activity, as well as overexpression, is present in a wide variety of cancers such as gastric, colorectal, renal, stomach, esophagus, lung and breast. PLD provides survival signals and is involved in migration, adhesion and invasion of cancer cells, and all are increased during PLD upregulation or, conversely, they are decreased during PLD loss of function. Even-though the end results of PLD action as relates to downstream signaling mechanisms are still currently being elucidated, invasion, a pre-requisite for metastasis, is directly affected by PLD. This review will introduce the classical mammalian PLD’s, PLD1 and PLD2, followed by the mechanisms of intracellular regulation and a status of current investigation in the crucial involvement of PLD in cancer, mostly through its role in cell migration, invasion and metastasis, that has grown exponentially in the last few years.

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“…It might also be that limiting choline uptake and availability drives up the expression and activity of other PC-generating pathways (PEMT and PC degradation via phospholipases) to scavenge the PC necessary for viral replication. Interestingly, phospholipase D, which cleaves existing PC to yield free choline and phosphatidic acid, is upregulated in an in vitro model of HCV [55].…”

Section: Discussionmentioning

confidence: 99%

In vitrohepatitis C virus infection and hepatic choline metabolism

Odai

O’Dwyer

Steenbergen

et al. 2019

Preprint

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Choline is an essential nutrient required for normal neuronal and muscular development, as well as homeostatic regulation of hepatic metabolism. In the liver, choline is incorporated into the main eukaryotic phospholipid, phosphatidylcholine (PC) and can enter one carbon metabolism via mitochondrial oxidation. Hepatitis C virus (HCV) is a hepatotropic positive-strand RNA virus that similar to other positive-strand RNA viruses can impact phospholipid metabolism. In the current study we sought to interrogate the link between choline transport and early HCV infection. Namely, we aimed to investigate how HCV modulates markers of choline metabolism following in vitro infection, while subsequently assessing how the inhibition of choline uptake and metabolism upon concurrent HCV infection may alter early viral replication. Finally, we assessed whether these parameters were consistent between cells cultured in fetal bovine serum (FBS) or human serum (HS), conditions known to differentially affect in vitro HCV infection. We observed that choline transport in FBS-cultured Huh7.5 cells is facilitated by the intermediate affinity transporter choline transporter-like family (CTL), and that CTL1 expression and the incorporation of choline into PC is diminished in 24 h infected FBScultured cells. Reciprocally, limiting the availability of choline for PC synthesis resulted in increased HCV replication at this early stage. In chronically HS-cultured Huh7.5 cells, there were no differences in the expression of choline transporters upon HCV infection or alterations to viral replication when choline transport was inhibited compared to control treatments. However, inhibiting choline uptake and metabolism in this system significantly impaired the production of infectious virions in HS-cultured cells. These results suggest that in addition to a known role of choline kinase, the transport of choline, potentially via CTL1, might also represent an important and regulated process during HCV infection.3

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Phospholipase D activity is elevated in hepatitis C virus core protein-transformed NIH3T3 mouse fibroblast cells

Abstract: A bstract H epatitis C V irus (H CV

Cited by 11 publications

References 32 publications

Role for ADP Ribosylation Factor 1 in the Regulation of Hepatitis C Virus Replication

Role for ADP Ribosylation Factor 1 in the Regulation of Hepatitis C Virus Replication

Phosphatidic acid, phospholipase D and tumorigenesis

In vitrohepatitis C virus infection and hepatic choline metabolism

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