The lipid droplet-associated protein perilipin 3 facilitates hepatitis C virus-driven hepatic steatosis

Ferguson, Daniel; Zhang, Jun; Davis, Matthew; Helsley, Robert N; Vedin, Lise Lotte; Lee, Richard G.; Crooke, Rosanne M.; Graham, Mark; Allende, Daniela S.; Parini, Paolo; Brown, J. Mark

doi:10.1194/jlr.m073734

Cited by 28 publications

(21 citation statements)

References 72 publications

(82 reference statements)

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“…However, LDs proteins also play an important role in this process. In the absence of PLIN3, HCV core protein-induced steatosis does not occur ( Ferguson et al, 2017 ). Moreover, core association to LDs leads to an inhibition of lipolysis by interfering with the activity of adipose triacylglycerol lipase (ATGL), the enzyme responsible for the first step of degradation of TAG.…”

Section: Lds Role In Flaviviridae Infectionsmentioning

confidence: 99%

Methods for Lipid Droplet Biophysical Characterization in Flaviviridae Infections

Martins

Santos

2018

Front. Microbiol.

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Lipid droplets (LDs) are intracellular organelles for neutral lipid storage, originated from the endoplasmic reticulum. They play an essential role in lipid metabolism and cellular homeostasis. In fact, LDs are complex organelles, involved in many more cellular processes than those initially proposed. They have been extensively studied in the context of LD-associated pathologies. In particular, LDs have emerged as critical for virus replication and assembly. Viruses from the Flaviviridae family, namely dengue virus (DENV), hepatitis C virus (HCV), West Nile virus (WNV), and Zika virus (ZIKV), interact with LDs to usurp the host lipid metabolism for their own viral replication and pathogenesis. In general, during Flaviviridae infections it is observed an increasing number of host intracellular LDs. Several viral proteins interact with LDs during different steps of the viral life cycle. The HCV core protein and DENV capsid protein, extensively interact with LDs to regulate their replication and assembly. Detailed studies of LDs in viral infections may contribute for the development of possible inhibitors of key steps of viral replication. Here, we reviewed different techniques that can be used to characterize LDs isolated from infected or non-infected cells. Microscopy studies have been commonly used to observe LDs accumulation and localization in infected cell cultures. Fluorescent dyes, which may affect LDs directly, are widely used to probe LDs but there are also approaches that do not require the use of fluorescence, namely stimulated Raman scattering, electron and atomic force microscopy-based approaches. These three are powerful techniques to characterize LDs morphology. Raman scattering microscopy allows studying LDs in a single cell. Electron and atomic force microscopies enable a better characterization of LDs in terms of structure and interaction with other organelles. Other biophysical techniques, such as dynamic light scattering and zeta potential are also excellent to characterize LDs in terms of size in a simple and fast way and test possible LDs interaction with viral proteins. These methodologies are reviewed in detail, in the context of viral studies.

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Section: Lds Role In Flaviviridae Infectionsmentioning

confidence: 99%

Methods for Lipid Droplet Biophysical Characterization in Flaviviridae Infections

Martins

Santos

2018

Front. Microbiol.

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“…The interaction between the HCV capsid protein and LDs is critical for this development. An LD membrane protein, perilipin 3, regulates the capsid-induced steatosis, indicating host LD-associated proteins as an effective preventive measure of HCV-induced pathology (Ferguson et al, 2017 ).…”

Section: Influence Of Ld Metabolism On the Virus Life Cyclementioning

confidence: 99%

Modulation of Lipid Droplet Metabolism—A Potential Target for Therapeutic Intervention in Flaviviridae Infections

2017

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Lipid droplets (LDs) are endoplasmic reticulum (ER)-related dynamic organelles that store and regulate fatty acids and neutral lipids. They play a central role in cellular energy storage, lipid metabolism and cellular homeostasis. It has become evident that viruses have co-evolved in order to exploit host lipid metabolic pathways. This is especially characteristic of the Flaviviridae family, including hepatitis C virus (HCV) and several flaviviruses. Devoid of an appropriate lipid biosynthetic machinery of their own, these single-strand positive-sense RNA viruses can induce dramatic changes in host metabolic pathways to establish a favorable environment for viral multiplication and acquire essential components to facilitate their assembly and traffic. Here we have reviewed the current knowledge on the intracellular life cycle of those from the Flaviviridae family, with particular emphasis on HCV and dengue virus (DENV), and their association with the biosynthesis and metabolism of LDs, with the aim to identify potential antiviral targets for development of novel therapeutic interventions.

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“…The mechanism of formation of LBs in host cells is a highly regulated event. Upon leukocytes activation LBs are formed rapidly in response to different stimuli and pathological conditions, such as infection by distinct pathogens: mycobacteria ( Cardona and Ausina, 2000 ; D’Avila et al, 2006 ; Almeida et al, 2009 , 2014 ; Mattos et al, 2010 , 2011 ), virus ( Ferguson et al, 2017 ) or protozoan, such as T. cruzi ( Melo et al, 2003 ; D’Avila et al, 2011 ), Leishmania major ( Rabhi et al, 2016 ), L. amazonensis ( Pinheiro et al, 2009 ; Lecoeur et al, 2013 ), and Toxoplasma gondii ( Gomes et al, 2014 ; Mota et al, 2014 ).…”

Section: Lipid Body Formation During T Cruzi Infementioning

confidence: 99%

Lipid Bodies as Sites of Prostaglandin E2 Synthesis During Chagas Disease: Impact in the Parasite Escape Mechanism

et al. 2018

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During Chagas disease, the Trypanosoma cruzi can induce some changes in the host cells in order to escape or manipulate the host immune response. The modulation of the lipid metabolism in the host phagocytes or in the parasite itself is one feature that has been observed. The goal of this mini review is to discuss the mechanisms that regulate intracellular lipid body (LB) biogenesis in the course of this parasite infection and their meaning to the pathophysiology of the disease. The interaction host–parasite induces LB (or lipid droplet) formation in a Toll-like receptor 2-dependent mechanism in macrophages and is enhanced by apoptotic cell uptake. Simultaneously, there is a lipid accumulation in the parasite due to the incorporation of host fatty acids. The increase in the LB accumulation during infection is correlated with an increase in the synthesis of PGE2 within the host cells and the parasite LBs. Moreover, the treatment with fatty acid synthase inhibitor C75 or non-steroidal anti-inflammatory drugs such as NS-398 and aspirin inhibited the LB biogenesis and also induced the down modulation of the eicosanoid production and the parasite replication. These findings show that LBs are organelles up modulated during the course of infection. Furthermore, the biogenesis of the LB is involved in the lipid mediator generation by both the macrophages and the parasite triggering escape mechanisms.

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The lipid droplet-associated protein perilipin 3 facilitates hepatitis C virus-driven hepatic steatosis

Cited by 28 publications

References 72 publications

Methods for Lipid Droplet Biophysical Characterization in Flaviviridae Infections

Methods for Lipid Droplet Biophysical Characterization in Flaviviridae Infections

Modulation of Lipid Droplet Metabolism—A Potential Target for Therapeutic Intervention in Flaviviridae Infections

Lipid Bodies as Sites of Prostaglandin E2 Synthesis During Chagas Disease: Impact in the Parasite Escape Mechanism

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