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Hepatitis C virus lipids

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https://www.readbyqxmd.com/read/28088354/uncovering-oxysterol-binding-protein-osbp-as-a-target-of-the-anti-enteroviral-compound-ttp-8307
#1
Lucian Albulescu, Joëlle Bigay, Bishyajit Biswas, Marion Weber-Boyvat, Cristina M Dorobantu, Leen Delang, Hilde M van der Schaar, Young-Sik Jung, Johan Neyts, Vesa M Olkkonen, Frank J M van Kuppeveld, Jeroen R P M Strating
The genus Enterovirus (e.g. poliovirus, coxsackievirus, rhinovirus) of the Picornaviridae family of positive-strand RNA viruses includes many important pathogens linked to a range of acute and chronic diseases for which no approved antiviral therapy is available. Targeting a step in the life cycle that is highly conserved provides an attractive strategy for developing broad-range inhibitors of enterovirus infection. A step that is currently explored as a target for the development of antivirals is the formation of replication organelles, which support replication of the viral genome...
January 11, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28077274/the-role-and-regulation-of-the-peroxisome-proliferator-activated-receptor-alpha-in-human-liver
#2
REVIEW
Sander Kersten, Rinke Stienstra
The peroxisome proliferator-activated receptor α (PPARα) is a ligand-activated transcription factor that is abundantly expressed in liver. PPARα is activated by fatty acids and various other lipid species, as well as by a class of chemicals referred to as peroxisome proliferators. Studies in mice have shown that PPARα serves as the master regulator of hepatic lipid metabolism during fasting. In addition, PPARα suppresses inflammation and the acute phase response. Comparatively little is known about PPARα in human liver...
January 7, 2017: Biochimie
https://www.readbyqxmd.com/read/28073421/-research-advances-in-the-role-of-sphingolipids-in-hcv-and-hbv-life-cycles
#3
J Y Zhang, Z P Duan, J L Zhang, S J Zheng
Sphingolipids and their metabolites are not only important structural molecules of the cell membrane, but also involved in all phases of viral life cycle, including cell adhesion, membrane fusion, viral replication, viral assembly, intracellular transport, protein sorting, and exocytosis. In recent years, sphingolipids have become one of the focuses of lipid research. This article reviews the role of sphingolipids in the life cycles of hepatitis C virus and hepatitis B virus with reference to recent research achievements in China and foreign countries...
December 20, 2016: Zhonghua Gan Zang Bing za Zhi, Zhonghua Ganzangbing Zazhi, Chinese Journal of Hepatology
https://www.readbyqxmd.com/read/28056752/inhibiting-the-secretion-of-hepatitis-b-surface-antigen-hbsag-to-treat-hepatitis-b-infection-a-review
#4
Simon D Baugh
Chronic Hepatitis B is a major global health issue, and has no known cure. Currently there are over 240 million people infected with the disease, and it leads to the death of over 686,000 people each year. A total of seven treatments which help to control the disease are currently available: interferon-based treatments (pegasys, and interferon alpha), and nucleoside and nucleotide analogs (Viread, Baraclude, Tyzeka, Hepsera, Epivir-HBV), but all require continuing treatment to maintain control of the disease...
January 4, 2017: Infectious Disorders Drug Targets
https://www.readbyqxmd.com/read/28053108/a-point-mutation-in-the-n-terminal-amphiphathic-helix-%C3%AE-0-in-ns3-promotes-hcv-assembly-by-altering-core-localization-to-er-and-facilitating-virus-budding
#5
Yu Yan, Ying He, Bertrand Boson, Xuesong Wang, François-Loïc Cosset, Jin Zhong
: The assembly of hepatitis C virus (HCV), a complicated process in which many viral and cellular factors are involved, has not been thoroughly deciphered. NS3 is a multifunctional protein that contains an N-terminal amphipathic α helix (denoted helix α0), whichis crucial for the membrane association and stability of NS3 protein, followed by a serine protease domain and a C-terminal helicase/NTPase domain. NS3 participates in HCV assembly likely through its C-terminal helicase domain where all reported adaptive mutations enhancing virion assembly reside...
January 4, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28050236/hepatitis-c-eradication-with-sofosbuvir-leads-to-significant-metabolic-changes
#6
Amilcar L Morales, Zachary Junga, Manish B Singla, Maria Sjogren, Dawn Torres
AIM: To assess the effect of sofosbuvir (SOF) based regimens on glycemic and lipid control. METHODS: This is a retrospective analysis of hepatitis C virus (HCV)-infected patients treated and cured with a SOF regimen [SOF/ribavirin/interferon, SOF/simeprevir, or SOF/ledipasvir (LDV) ± ribavirin] from January 2014 to March 2015. Patients with hemoglobin A1C (HbA1C) and lipid panels within six months before and six months after therapy were identified and included in our study...
December 18, 2016: World Journal of Hepatology
https://www.readbyqxmd.com/read/28035714/gfp-tagged-apolipoprotein-e-a-useful-marker-for-the-study-of-hepatic-lipoprotein-egress
#7
Constantin N Takacs, Ursula Andreo, Rachel L Belote, Joan Pulupa, Margaret A Scull, Caroline E Gleason, Charles M Rice, Sanford M Simon
Apolipoprotein E (ApoE), a component of very-low-density and high-density lipoproteins, participates in many aspects of lipid transport in the bloodstream. Underscoring its important functions, ApoE isoforms have been associated with metabolic and circulatory disease. ApoE is also incorporated into hepatitis C virus (HCV) particles, and promotes their production and infectivity. Live cell imaging analysis of ApoE behavior during secretion from producing cells thus has the potential to reveal important details regarding lipoprotein and HCV particle biogenesis and secretion from cells...
December 30, 2016: Traffic
https://www.readbyqxmd.com/read/28018102/apolipoprotein-b100-is-required-for-hepatitis-c-infectivity-and-mipomersen-inhibits-hepatitis-c
#8
Esperance A K Schaefer, James Meixiong, Christina Mark, Amy Deik, Daniel L Motola, Dahlene Fusco, Andrew Yang, Cynthia Brisac, Shadi Salloum, Wenyu Lin, Clary B Clish, Lee F Peng, Raymond T Chung
AIM: To characterize the role of apolipoprotein B100 (apoB100) in hepatitis C viral (HCV) infection. METHODS: In this study, we utilize a gene editing tool, transcription activator-like effector nucleases (TALENs), to generate human hepatoma cells with a stable genetic deletion of APOB to assess of apoB in HCV. Using infectious cell culture-competent HCV, viral pseudoparticles, replicon models, and lipidomic analysis we determined the contribution of apoB to each step of the viral lifecycle...
December 7, 2016: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28004946/fluorescent-inhibitors-as-tools-to-characterize-enzymes-case-study-of-the-lipid-kinase-phosphatidylinositol-4-kinase-iii%C3%AE-pi4kb
#9
Jana Humpolickova, Ivana Mejdrová, Marika Matousova, Radim Nencka, Evzen Boura
The lipid kinase phosphatidylinositol 4-kinase IIIβ (PI4KB) is an essential host factor for many positive-sense single-stranded RNA (+RNA) viruses including human pathogens hepatitis C virus (HCV), Severe acute respiratory syndrome (SARS), coxsackie viruses, and rhinoviruses. Inhibitors of PI4KB are considered to be potential broad-spectrum virostatics, and it is therefore critical to develop a biochemical understanding of the kinase. Here, we present highly potent and selective fluorescent inhibitors that we show to be useful chemical biology tools especially in determination of dissociation constants...
December 22, 2016: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27991882/tuning-a-cellular-lipid-kinase-activity-adapts-hepatitis-c-virus-to-replication-in-cell-culture
#10
Christian Harak, Max Meyrath, Inés Romero-Brey, Christian Schenk, Claire Gondeau, Philipp Schult, Katharina Esser-Nobis, Mohsan Saeed, Petra Neddermann, Paul Schnitzler, Daniel Gotthardt, Sofia Perez-Del-Pulgar, Christoph Neumann-Haefelin, Robert Thimme, Philip Meuleman, Florian W R Vondran, Raffaele De Francesco, Charles M Rice, Ralf Bartenschlager, Volker Lohmann
With a single exception, all isolates of hepatitis C virus (HCV) require adaptive mutations to replicate efficiently in cell culture. Here, we show that a major class of adaptive mutations regulates the activity of a cellular lipid kinase, phosphatidylinositol 4-kinase IIIα (PI4KA). HCV needs to stimulate PI4KA to create a permissive phosphatidylinositol 4-phosphate-enriched membrane microenvironment in the liver and in primary human hepatocytes (PHHs). In contrast, in Huh7 hepatoma cells, the virus must acquire loss-of-function mutations that prevent PI4KA overactivation...
December 19, 2016: Nature Microbiology
https://www.readbyqxmd.com/read/27981599/hiv-infected-and-uninfected-adults-with-non-genotype-3-hepatitis-c-virus-have-less-hepatic-steatosis-than-adults-with-neither-infection
#11
Jennifer C Price, Yifei Ma, Rebecca Scherzer, Natalie Korn, Kyle Tillinghast, Marion G Peters, Susan M Noworolski, Phyllis C Tien
BACKGROUND: Hepatic steatosis (HS) is common in persons with hepatitis C virus (HCV) and human immunodeficiency virus (HIV) infections, but the independent contributions of HCV and HIV to HS is unclear. METHODS: Magnetic resonance imaging and spectroscopy were used to measure visceral adipose tissue (VAT) and liver fat fraction (LFF)[total lipids/(total lipids+water)] in 356 adults: 57 HCV-monoinfected, 70 HIV/HCV-coinfected, 122 HIV-monoinfected, and 107 HIV/HCV-uninfected...
December 16, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/27941027/the-lipid-droplet-associated-protein-perilipin-3-facilitates-hepatitis-c-virus-driven-hepatic-steatosis
#12
Daniel Ferguson, Jun Zhang, Matthew A Davis, Robert N Helsley, Lise-Lotte Vedin, Richard G Lee, Rosanne M Crooke, Mark J Graham, Paolo Parini, J Mark Brown
Hepatitis C Virus (HCV) is an enveloped RNA virus responsible for 170 million cases of viral hepatitis worldwide. Over 50% of chronically infected HCV patients develop hepatic steatosis, and steatosis can be induced by expression of HCV core protein (core) alone. Additionally, core must associate with cytoplasmic lipid droplets (LD) for steatosis development and viral particle assembly. Given the LD is an important component of hepatic lipid storage, and serves as a platform for HCV particle assembly; this dynamic subcellular organelle is a gatekeeper in the pathogenesis of viral hepatitis...
December 10, 2016: Journal of Lipid Research
https://www.readbyqxmd.com/read/27933788/desmosterol-increases-lipid-bilayer-fluidity-during-hepatitis-c-virus-infection
#13
Deirdre A Costello, Valerie A Villareal, Priscilla L Yang
Hepatitis C virus (HCV) uniquely affects desmosterol homeostasis by increasing its intracellular abundance and affecting its localization. These effects are important for productive viral replication because the inhibition of desmosterol synthesis has an antiviral effect that can be rescued by the addition of exogenous desmosterol. Here, we use subgenomic replicons to show that desmosterol has a major effect on the replication of HCV JFH1 RNA. Fluorescence recovery after photobleaching (FRAP) experiments performed with synthetic supported lipid bilayers demonstrate that the substitution of desmosterol for cholesterol significantly increases the lipid bilayer fluidity, especially in the presence of saturated phospholipids and ceramides...
November 11, 2016: ACS Infectious Diseases
https://www.readbyqxmd.com/read/27830380/recovery-of-pan-genotypic-and-genotype-specific-amino-acid-alterations-in-chronic-hepatitis-c-after-viral-clearance-transition-at-the-crossroad-of-metabolism-and-immunity
#14
Ming-Ling Chang, Mei-Ling Cheng, Su-Wei Chang, Hsiang-Yu Tang, Cheng-Tang Chiu, Chau-Ting Yeh, Ming-Shi Shiao
Recovery of amino acid (AA) metabolism and the associated clinical implications in chronic hepatitis C (CHC) patients with sustained virological response (SVR) following anti-hepatitis C virus (HCV) therapy remains elusive. A prospective cohort study was conducted on 222 CHC patients with SVR. Eighty-two age-matched male genotype 1 (G1) and G2 patients underwent paired serum metabolomics analyses with liquid chromatography-tandem mass spectrometry to examine AAs before and 24 weeks after anti-HCV therapy. Before anti-HCV therapy, G1 patients had a higher HCV RNA level than G2 patients...
November 10, 2016: Amino Acids
https://www.readbyqxmd.com/read/27794207/lipid-droplet-hijacking-by-intracellular-pathogens
#15
REVIEW
Philippe Roingeard, Rossana C N Melo
Lipid droplets were long considered to be simple storage structures, but they have recently been shown to be dynamic organelles involved in diverse biological processes, including emerging roles in innate immunity. Various intracellular pathogens, including viruses, bacteria, and parasites, specifically target host lipid droplets during their life cycle. Viruses such as hepatitis C, dengue, and rotaviruses use lipid droplets as platforms for assembly. Bacteria, such as mycobacteria and Chlamydia, and parasites, such as trypanosomes, use host lipid droplets for nutritional purposes...
January 2017: Cellular Microbiology
https://www.readbyqxmd.com/read/27788588/identification-of-circulating-protein-biomarkers-in-patients-with-hepatocellular-carcinoma-concomitantly-infected-with-chronic-hepatitis-c-virus
#16
Abdel-Hady Ali Abdel-Wahab, Medhat S El-Halawany, Ahmad A Emam, Ammar Elfiky, Zakaria Y Abd Elmageed
CONTEXT: The incidence rate of hepatocellular carcinoma (HCC) is higher in developing countries, and most cases are associated with chronic hepatitis C virus (HCV) infection. OBJECTIVE: To evaluate the circulating proteins as liver biomarkers for identification of HCC associated with HCV infection in Egyptian patients using LC-MS/MS analysis. METHODS: Blood sera were collected from 31 HCC patients and the fractionated proteins were subjected to LC-MS/MS analysis...
October 28, 2016: Biomarkers: Biochemical Indicators of Exposure, Response, and Susceptibility to Chemicals
https://www.readbyqxmd.com/read/27776194/rna-seq-based-analysis-of-differential-gene-expression-associated-with-hepatitis-c-virus-infection-in-a-cell-culture
#17
Anna Hojka-Osinska, Lucyna Budzko, Agnieszka Zmienko, Agnieszka Rybarczyk, Patrick Maillard, Agata Budkowska, Marek Figlerowicz, Paulina Jackowiak
Hepatitis C virus (HCV) infection is one of the major causes of chronic liver diseases. Unfortunately, the mechanisms of HCV infection-induced liver injury and host-virus interactions are still not well recognized. To better understand these processes we determined the changes in the host gene expression that occur during HCV infection of Huh-7.5 cells. As a result, we identified genes that may contribute to the immune and metabolic cellular responses to infection. Pathway enrichment analysis indicated that HCV induced an increased expression of genes involved in mitogen-activated protein kinases signaling, adipocytokine signaling, cell cycle and nitrogen metabolism...
2016: Acta Biochimica Polonica
https://www.readbyqxmd.com/read/27773935/alisol-b-23-acetate-protects-against-non-alcoholic-steatohepatitis-in-mice-via-farnesoid-x-receptor-activation
#18
Qiang Meng, Xing-Ping Duan, Chang-Yuan Wang, Zhi-Hao Liu, Peng-Yuan Sun, Xiao-Kui Huo, Hui-Jun Sun, Jin-Yong Peng, Ke-Xin Liu
Alisol B 23-acetate (AB23A) is a natural triterpenoid isolated from the traditional Chinese medicine rhizoma alismatis, which exhibits a number of pharmacological activities, including anti-hepatitis virus, anti-cancer and antibacterial effects. In this study we examined whether AB23A protected against non-alcoholic steatohepatitis (NASH) in mice, and the mechanisms underlying the protective effects. NASH was induced in mice fed a methionine and choline-deficient (MCD) diet for 4 weeks. The mice were simultaneously treated with AB23A (15, 30, and 60 mg·kg(-1)·d(-1), ig) for 4 weeks...
January 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/27773535/n6-methyladenosine-in-flaviviridae-viral-rna-genomes-regulates-infection
#19
Nandan S Gokhale, Alexa B R McIntyre, Michael J McFadden, Allison E Roder, Edward M Kennedy, Jorge A Gandara, Sharon E Hopcraft, Kendra M Quicke, Christine Vazquez, Jason Willer, Olga R Ilkayeva, Brittany A Law, Christopher L Holley, Mariano A Garcia-Blanco, Matthew J Evans, Mehul S Suthar, Shelton S Bradrick, Christopher E Mason, Stacy M Horner
The RNA modification N6-methyladenosine (m(6)A) post-transcriptionally regulates RNA function. The cellular machinery that controls m(6)A includes methyltransferases and demethylases that add or remove this modification, as well as m(6)A-binding YTHDF proteins that promote the translation or degradation of m(6)A-modified mRNA. We demonstrate that m(6)A modulates infection by hepatitis C virus (HCV). Depletion of m(6)A methyltransferases or an m(6)A demethylase, respectively, increases or decreases infectious HCV particle production...
November 9, 2016: Cell Host & Microbe
https://www.readbyqxmd.com/read/27742550/transient-elastography-as-a-noninvasive-assessment-tool-for-hepatopathies-of-different-etiology-in-pediatric-type-1-diabetes-mellitus
#20
Zeinab A Elkabbany, Nancy S Elbarbary, Eman A Ismail, Nesrine A Mohamed, Dina Ragab, Shereen Abdel Alem, Yasmine M Ezzat, Sarah S Maurice, Noha U Hashem
AIM: To identify the prevalence and effect of hepatopathies of different etiologies among pediatric patients with type 1 diabetes mellitus (T1DM) using transient elastography (TE) and its relation to glycemic control. METHODS: One hundred T1DM patients were studied focusing on liver functions, fasting lipid profile, hemoglobin A1c (HbA1c), hepatitis C virus (HCV), serum immunoglobulins, autoimmune antibodies; anti-nuclear antibody (ANA), anti-smooth muscle antibody (ASMA), and anti-liver kidney microsomal antibody (anti-LKM)...
January 2017: Journal of Diabetes and its Complications
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