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https://www.readbyqxmd.com/read/28630011/interplay-between-hepatitis-c-virus-and-lipid-metabolism-during-virus-entry-and-assembly
#1
REVIEW
Muriel Lavie, Jean Dubuisson
Hepatitis C virus (HCV) infection is a major public health problem worldwide. In most cases, HCV infection becomes chronic, leading to the development of liver diseases that range from fibrosis to cirrhosis and hepatocellular carcinoma. Due to its medical importance, the HCV life cycle has been deeply characterized, and a unique feature of this virus is its interplay with lipids. Accordingly, all the steps of the virus life cycle are influenced by the host lipid metabolism. Indeed, due to their association with host lipoproteins, HCV particles have a unique lipid composition...
June 16, 2017: Biochimie
https://www.readbyqxmd.com/read/28625086/hepatitis-c-virus-apolipoprotein-interactions-molecular-mechanisms-and-clinical-impact
#2
Emilie Crouchet, Thomas F Baumert, Catherine Schuster
Chronic hepatitis C virus (HCV) infection is a leading cause of cirrhosis, hepatocellular carcinoma and liver failure. Moreover, chronic HCV infection is associated with liver steatosis and metabolic disorders. With 130-150 million people chronically infected in the world, HCV infection represents a major public health problem. One hallmark on the virus is its close link with hepatic lipid and lipoprotein metabolism. Areas covered: HCV is associated with lipoprotein components such as apolipoproteins. These interactions play a key role in the viral life cycle, viral persistence and pathogenesis of liver disease...
June 17, 2017: Expert Review of Proteomics
https://www.readbyqxmd.com/read/28623358/the-role-of-pten-hcv-core-interaction-in-hepatitis-c-virus-replication
#3
Qi Wu, Zhubing Li, Paul Mellor, Yan Zhou, Deborah H Anderson, Qiang Liu
Hepatitis C virus (HCV) infection leads to severe liver diseases including hepatocellular carcinoma (HCC). Phosphatase and tensin homolog deleted on chromosome 10 (PTEN), a tumour suppressor, is frequently mutated or deleted in HCC tumors. PTEN has previously been demonstrated to inhibit HCV secretion. In this study, we determined the effects of PTEN on the other steps in HCV life cycle, including entry, translation, and replication. We showed that PTEN inhibits HCV entry through its lipid phosphatase activity...
June 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28615303/favouring-modulation-of-circulating-lipoproteins-and-lipid-loading-capacity-by-direct-antiviral-agents-grazoprevir-elbasvir-or-ledipasvir-sofosbuvir-treatment-against-chronic-hcv-infection
#4
Hung-Yu Sun, Pin-Nan Cheng, Chiung-Ying Tseng, Wei-Jen Tsai, Yen-Cheng Chiu, Kung-Chia Young
OBJECTIVE: Lipid homoeostasis is disturbed in patients with HCV infection. Direct-acting antiviral agent (DAA) treatment eradicates chronic HCV viraemia, but the dynamics of lipid components remain elusive. This study investigates the clinical manifestation and mechanistic relevance of plasma triglyceride (TG), cholesterol (Chol), lipoproteins and apolipoproteins (apos) after DAA treatment. DESIGN: Twenty-four patients with chronic genotype 1 (GT1) HCV treated with elbasvir/grazoprevir or ledipasvir/sofosbuvir for 12 weeks, and followed-up thereafter, were recruited...
June 14, 2017: Gut
https://www.readbyqxmd.com/read/28611396/coupling-neutron-reflectivity-with-cell-free-protein-synthesis-to-probe-membrane-protein-structure-in-supported-bilayers
#5
Thomas Soranzo, Donald K Martin, Jean-Luc Lenormand, Erik B Watkins
The structure of the p7 viroporin, an oligomeric membrane protein ion channel involved in the assembly and release of the hepatitis C virus, was determined from proteins expressed and inserted directly into supported model lipid membranes using cell-free protein expression. Cell-free protein expression allowed (i ) high protein concentration in the membrane, (ii ) control of the protein's isotopic constitution, and (iii ) control over the lipid environment available to the protein. Here, we used cell-free protein synthesis to directly incorporate the hepatitis C virus (HCV) p7 protein into supported lipid bilayers formed from physiologically relevant lipids (POPC or asolectin) for both direct structural measurements using neutron reflectivity (NR) and conductance measurements using electrical impedance spectroscopy (EIS)...
June 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28594932/ns5a-inhibitors-unmask-differences-in-functional-replicase-complex-half-life-between-different-hepatitis-c-virus-strains
#6
Tiffany Benzine, Ryan Brandt, William C Lovell, Daisuke Yamane, Petra Neddermann, Raffaele De Francesco, Stanley M Lemon, Alan S Perelson, Ruian Ke, David R McGivern
Hepatitis C virus (HCV) RNA is synthesized by the replicase complex (RC), a macromolecular assembly composed of viral non-structural proteins and cellular co-factors. Inhibitors of the HCV NS5A protein block formation of new RCs but do not affect RNA synthesis by pre-formed RCs. Without new RC formation, existing RCs turn over and are eventually lost from the cell. We aimed to use NS5A inhibitors to estimate the half-life of the functional RC of HCV. We compared different cell culture-infectious strains of HCV that may be grouped based on their sensitivity to lipid peroxidation: robustly replicating, lipid peroxidation resistant (LPOR) viruses (e...
June 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28587063/a-relative-deficiency-of-lysosomal-acid-lypase-activity-characterizes-non-alcoholic-fatty-liver-disease
#7
Francesco Tovoli, Lucia Napoli, Giulia Negrini, Sergio D'Addato, Giulia Tozzi, Jessica D'Amico, Fabio Piscaglia, Luigi Bolondi
Lysosomal acid lipase (LAL) is a key enzyme in lipid metabolism. Initial reports have suggested a role for a relative acquired LAL deficiency in non-alcoholic fatty liver disease (NAFLD)-however, it is still unclear whether this mechanism is specific for NAFLD. We aimed to determine LAL activity in a cohort of NAFLD subjects and in a control group of hepatitis C virus (HCV)-infected patients, investigating the role of liver cirrhosis. A total of 81 patients with a diagnosis of NAFLD, and 78 matched controls with HCV-related liver disease were enrolled...
May 25, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28574577/pcsk9-and-infection-a-potentially-useful-or-dangerous-association
#8
REVIEW
Farzad Kahdemi, Amir Abbas Momtazi-Borojeni, Željko Reiner, Maciej Banach, Khalid Al Rasadi, Amirhossein Sahebkar
Elevated plasma low-density lipoprotein-cholesterol (LDL-C) concentration is the most important risk factor for atherosclerotic cardiovascular diseases. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a ubiquitously expressed serine proteinase which plays a key role in cholesterol metabolism, but has been found to be implicated in some other lipid-independent physiological processes. In this review, the role of PCSK9 was evaluated not only concerning lipid metabolism but also hepatitis C virus (HCV) infection, bacterial infections/sepsis and septic shock...
June 2, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28566716/glycogen-synthase-kinase-3%C3%AE-inhibitors-prevent-hepatitis-c-virus-release-assembly-through-perturbation-of-lipid-metabolism
#9
Mohammed A Sarhan, Mohamed S Abdel-Hakeem, Andrew L Mason, D Lorne Tyrrell, Michael Houghton
Direct acting antivirals against hepatitis C virus (HCV) have markedly improved cure rates in the past few years. However, they are expensive, with only few targeting host cell factors, and affecting virus assembly and release. Huh7.5 cells infected with a JFH-1 clone of HCV were treated with two different glycogen synthase kinase (GSK3)-β inhibitors; AR-A014418 and lithium chloride. Intra- and extracellular HCV virions and specific infectivity was determined using real-time RT-PCR and TCID50, and changes in lipid production were identified by enzyme-linked immunoassay and mass spectrometry analyses...
May 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28566381/hepatitis-c-virus-subverts-human-choline-kinase-%C3%AE-to-bridge-pi4kiii%C3%AE-and-ns5a-and-upregulates-pi4kiii%C3%AE-activation-thereby-promoting-the-translocation-of-the-ternary-complex-to-the-er-for-viral-replication
#10
Mun-Teng Wong, Steve S Chen
In this study, we elucidated the mechanism by which human choline kinase-α (hCKα) interacts with nonstructural protein (NS)5A and phosphatidylinositol-4-kinase (PI4K)IIIα, the lipid kinase crucial for maintaining the integrity of virus-induced membranous webs, and modulates hepatitis C virus (HCV) replication. hCKα activity positively modulated PI-4-phosphate (PI4P) levels in HCV-expressing cells, and hCKα-mediated PI4P accumulation was abolished by AL-9, a PI4KIIIα-specific inhibitor. hCKα colocalized with NS5A and PI4KIIIα or PI4P, NS5A expression increased hCKα and PI4KIIIα colocalization, and hCKα formed a ternary complex with PI4KIIIα and NS5A, supporting the functional interplay of hCKα with PI4KIIIα and NS5A...
May 31, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28554802/influence-of-chemical-composition-on-biochemical-methane-potential-of-fruit-and-vegetable-waste
#11
Thiago Edwiges, Laercio Frare, Bruna Mayer, Leonardo Lins, Jin Mi Triolo, Xavier Flotats, Mônica Sarolli Silva de Mendonça Costa
This study investigates the influence of chemical composition on the biochemical methane potential (BMP) of twelve different batches of fruit and vegetable waste (FVW) with different compositions collected over one year. BMP ranged from 288 to 516LNCH4kgVS(-1), with significant statistical differences between means, which was explained by variations in the chemical composition over time. BMP was most strongly correlated to lipid content and high calorific values. Multiple linear regression was performed to develop statistical models to more rapidly predict methane potential...
May 26, 2017: Waste Management
https://www.readbyqxmd.com/read/28526563/live-cell-imaging-and-analysis-of-lipid-droplets-biogenesis-in-hcv-infected-cells
#12
Inbar Nevo-Yassaf, Marcos Lovelle, Yaacov Nahmias, Koret Hirschberg, Ella H Sklan
Lipid droplets (LDs) are regulated neutral lipid storage organelles having a central role in numerous cellular processes as well as in various pathologies such as metabolic disorders, immune responses and during pathogen infection. Several viruses were found to use the interface between the endoplasmic reticulum (ER) and LDs as the site for replication and assembly. Due to the growing significance of LDs, extensive efforts are made to study the mechanism and the dynamics of their formation and life history and how are these diverted or modified by pathogens...
May 16, 2017: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/28515296/hepatitis-c-virus-lipoviroparticles-hcv-lvp-assemble-in-the-endoplasmic-reticulum-er-and-bud-off-from-the-er-to-golgi-in-copii-vesicles
#13
Gulam H Syed, Mohsin Khan, Song Yang, Aleem Siddiqui
Hepatitis C virus (HCV) exists as a lipoprotein-virus hybrid lipoviroparticle (LVP). In vitro studies have demonstrated the importance of apolipoproteins in HCV secretion and infectivity leading to the notion that HCV co-opts the secretion of very-low density lipoprotein (VLDL) for its egress. However, our understanding of the mechanisms involved in virus particle assembly and egress, are still elusive. Biogenesis of VLDL particle occurs in the ER followed by subsequent lipidation in the ER and Golgi. Secretion of mature VLDL particles occurs through the Golgi secretory pathway...
May 17, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28484991/lipid-testing-in-infectious-diseases-possible-role-in-diagnosis-and-prognosis
#14
REVIEW
Sebastian Filippas-Ntekouan, Evangelos Liberopoulos, Moses Elisaf
INTRODUCTION: Acute infections lead to significant alterations in metabolic regulation including lipids and lipoproteins, which play a central role in the host immune response. In this regard, several studies have investigated the role of lipid levels as a marker of infection severity and prognosis. SCOPE OF REVIEW: We review here the role of lipids in immune response and the potential mechanisms underneath. Moreover, we summarize studies on lipid and lipoprotein alterations in acute bacterial, viral and parasitic infections as well as their diagnostic and prognostic significance...
May 8, 2017: Infection
https://www.readbyqxmd.com/read/28475247/exploration-of-potential-mechanisms-of-hcv-resistance-in-exposed-uninfected-intravenous-drug-users
#15
Isaac Thom Shawa, Daniel J Felmlee, Doha Hegazy, David A Sheridan, Matthew E Cramp
A rare outcome following exposure to hepatitis C virus (HCV) is a lack of observable infection as clinically measured by HCV RNA or HCV recognising antibodies. The population who exhibit this trait is termed exposed uninfected (EU). Increasing evidence has refined characterisation of these individuals, distinct from those who become infected but spontaneously clear HCV. Study of the EU population is highly pertinent for the discovery of antiviral mechanisms of resistance that can reveal antiviral therapeutic strategies...
May 5, 2017: Journal of Viral Hepatitis
https://www.readbyqxmd.com/read/28448054/lipid-droplet-isolation-for-quantitative-mass-spectrometry-analysis
#16
Kathrin Rösch, Marcel Kwiatkowski, Hartmut Schlüter, Eva Herker
Lipid droplets are vital to the replication of a variety of different pathogens, most prominently the Hepatitis C Virus (HCV), as the putative site of virion morphogenesis. Quantitative lipid droplet proteome analysis can be used to identify proteins that localize to or are displaced from lipid droplets under conditions such as virus infections. Here, we describe a protocol that has been successfully used to characterize the changes in the lipid droplet proteome following infection with HCV. We use Stable Isotope Labeling with Amino Acids in Cell Culture (SILAC) and thus label the complete proteome of one population of cells with "heavy" amino acids to quantitate the proteins by mass spectrometry...
April 17, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28444148/risk-of-acute-myocardial-infarction-among-hcv-and-hcv-men-at-various-lipid-levels-results-from-erchives
#17
Adeel A Butt, Peng Yan, Kara W Chew, Judith Currier, Kathleen Corey, Raymond T Chung, Ashfaq Shuaib, Abdul-Badi Abou-Samra, Javed Butler, Matthew S Freiberg
Background: Risk of AMI among HCV+ versus HCV- persons with similar lipid levels is unknown. We determined incident AMI rates among HCV+ and HCV- men among various lipid strata. Methods: We created a propensity score matched (PSM) cohort, and a low cardiovascular disease (CVD) risk cohort. Primary outcome was incident AMI rates by HCV status in each lipid strata using National Cholesterol Program guidelines for lipid strata. Results: We identified 85,863 HCV+ and HCV- men in the PSM population...
April 24, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/28444147/hcv-associated-alterations-in-lipid-and-lipoprotein-levels-helpful-or-harmful-to-the-heart
#18
Phyllis C Tien
No abstract text is available yet for this article.
April 24, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/28443075/grim-19-restricts-hcv-replication-by-attenuating-intracellular-lipid-accumulation
#19
Jung-Hee Kim, Pil S Sung, Eun B Lee, Wonhee Hur, Dong J Park, Eui-Cheol Shin, Marc P Windisch, Seung K Yoon
Gene-associated with retinoid-interferon-induced mortality 19 (GRIM-19) targets multiple signaling pathways involved in cell death and growth. However, the role of GRIM-19 in the pathogenesis of hepatitis virus infections remains unexplored. Here, we investigated the restrictive effects of GRIM-19 on the replication of hepatitis C virus (HCV). We found that GRIM-19 protein levels were reduced in HCV-infected Huh7 cells and Huh7 cells harboring HCV replicons. Moreover, ectopically expressed GRIM-19 caused a reduction in both intracellular viral RNA levels and secreted viruses in HCVcc-infected cell cultures...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28437468/role-of-cleavage-at-the-core-e1-junction-of-hepatitis-c-virus-polyprotein-in-viral-morphogenesis
#20
Véronique Pène, Matthieu Lemasson, Francis Harper, Gérard Pierron, Arielle R Rosenberg
In hepatitis C virus (HCV) polyprotein sequence, core protein terminates with E1 envelope signal peptide. Cleavage by signal peptidase (SP) separates E1 from the complete form of core protein, anchored in the endoplasmic reticulum (ER) membrane by the signal peptide. Subsequent cleavage of the signal peptide by signal-peptide peptidase (SPP) releases the mature form of core protein, which preferentially relocates to lipid droplets. Both of these cleavages are required for the HCV infectious cycle, supporting the idea that HCV assembly begins at the surface of lipid droplets, yet SPP-catalyzed cleavage is dispensable for initiation of budding in the ER...
2017: PloS One
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