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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
#1
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/27788588/identification-of-circulating-protein-biomarkers-in-patients-with-hepatocellular-carcinoma-concomitantly-infected-with-chronic-hepatitis-c-virus
#2
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
#3
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...
October 25, 2016: Acta Biochimica Polonica
https://www.readbyqxmd.com/read/27773535/n6-methyladenosine-in-flaviviridae-viral-rna-genomes-regulates-infection
#4
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
#5
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)...
September 26, 2016: Journal of Diabetes and its Complications
https://www.readbyqxmd.com/read/27729393/ultrastructural-organisation-of-hcv-from-the-bloodstream-of-infected-patients-revealed-by-electron-microscopy-after-specific-immunocapture
#6
Eric Piver, Audrey Boyer, Julien Gaillard, Anne Bull, Elodie Beaumont, Philippe Roingeard, Jean-Christophe Meunier
OBJECTIVE: HCV particles are associated with very low-density lipoprotein components in chronically infected patients. These hybrid particles, or 'lipo-viro particles' (LVPs), are rich in triglycerides, and contain the viral RNA, the capsid protein, E1E2 envelope glycoproteins and apolipoproteins B and E. However, their specific ultrastructural organisation has yet to be determined. We developed a strategy for the preparation of any viral sample that preserves the native structure of the LVPs, facilitating their precise morphological characterisation...
October 11, 2016: Gut
https://www.readbyqxmd.com/read/27707921/the-intra-cellular-cholesterol-transport-inhibitor-u18666a-inhibits-the-exosome-dependent-release-of-mature-hepatitis-c-virus
#7
Fabian Elgner, Huimei Ren, Regina Medvedev, Daniela Ploen, Kiyoshi Himmelsbach, Klaus Boller, Eberhard Hildt
BACKGROUND: HCV particles are described as lipoviroparticles which are released similar to VLDLs. However, the release mechanism is still poorly understood; the canonical ERGIC pathway as well as the endosome-dependent release has been proposed. Recently, also the role of exosomes in the transmission of HCV has been reported. Only a minor fraction of the de novo synthesized lipoviroparticles are finally released by the infected cell. METHODS: To investigate the relevance of MVBs for viral morphogenesis and release, the MVB inhibitor U18666A was used...
October 5, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27685337/effect-of-antiviral-therapy-for-hcv-on-lipid-levels
#8
Stefan Mauss, Florian Berger, Malte H Wehmeyer, Patrick Ingiliz, Dietrich Hueppe, Thomas Lutz, Karl G Simon, Knud Schewe, Juergen K Rockstroh, Axel Baumgarten, Stefan Christensen
HCV has complex interactions with human lipid metabolism leading to down regulation of cholesterol levels. Interferon therapy has been shown to decrease cholesterol even further. With the availability of second generation direct acting antiviral agents (DAA) the effect of suppressing and eliminating HCV on lipid metabolism warrants reevaluation. 
Methods: Prospective German multicenter cohort on HCV- and HIV/HCV-infected patients treated with direct antiviral agents (GECCO). Lipids were assessed at baseline, during and after therapy...
September 29, 2016: Antiviral Therapy
https://www.readbyqxmd.com/read/27680885/rapid-increase-in-serum-low-density-lipoprotein-cholesterol-concentration-during-hepatitis-c-interferon-free-treatment
#9
Satoru Hashimoto, Hiroshi Yatsuhashi, Seigo Abiru, Kazumi Yamasaki, Atsumasa Komori, Shinya Nagaoka, Akira Saeki, Shinjiro Uchida, Shigemune Bekki, Yuki Kugiyama, Kazuyoshi Nagata, Minoru Nakamura, Kiyoshi Migita, Kazuhiko Nakao
BACKGROUND & AIM: We performed lipid analyses at the early period of therapy in patients with chronic hepatitis C who underwent interferon (IFN)-free direct-acting antiviral (DAA) treatment, and we attempted to identify the factors that contributed to a rapid increase in the patients' serum low-density lipoprotein cholesterol (LDL-C) concentration. METHODS: We retrospectively analyzed the cases of 100 consecutive patients with HCV infection treated at the National Hospital Organization Nagasaki Medical Center: 24 patients underwent daclatasvir (DCV) and asunaprevir (ASV) combination therapy (DCV/ASV) for 24 weeks, and the other 76 patients underwent ledipasvir and sofosbuvir combination therapy (LDV/SOF) for 12 weeks...
2016: PloS One
https://www.readbyqxmd.com/read/27677955/role-of-oxidative-stress-in-hepatitis-c-virus-induced-hepatocellular-carcinoma
#10
Na Fu, Hui Yao, Yuemin Nan, Liang Qiao
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide. Hepatitis C virus (HCV) infection is the predominant cause of chronic liver diseases and HCC, particularly in Western countries. Multiple molecular mechanisms are involved in the development and progression of HCV-related HCC, of which oxidative stress plays a pivotal role. HCV infection induces overproduction of reactive oxygen species (ROS) and impairs the function of endogenous antioxidants. Excessive amount of ROS directly damages DNA, lipids and proteins...
September 26, 2016: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/27665576/lipoprotein-lipase-liberates-free-fatty-acids-to-inhibit-hcv-infection-and-prevent-hepatic-lipid-accumulation
#11
Hung-Yu Sun, Chun-Chieh Lin, Pei-Ju Tsai, Wei-Jen Tsai, Jin-Ching Lee, Chiung-Wen Tsao, Pin-Nan Cheng, I-Chin Wu, Yen-Cheng Chiu, Ting-Tsung Chang, Kung-Chia Young
Lipoprotein lipase (LPL) has been identified as an anti-HCV host factor, but the cellular mechanism remains elusive. Here, we investigated the cellular mechanism of LPL involving in anti-HCV. The functional activation of peroxisome proliferator-activated receptor (PPAR) α signal by LPL transducing into hepatocytes were investigated in HCV-infected cells, primary human heaptocytes (PHHs), and in HCV-core transgenic mice. The result showed that the levels of transcriptional transactivity and nuclear translocation of PPARα in Huh7 cells and PHHs were elevated by physiologically ranged LPL treatment of either very-low-density lipoprotein or HCV particles...
September 25, 2016: Cellular Microbiology
https://www.readbyqxmd.com/read/27664407/anti-adipogenic-and-antiviral-effects-of-l-carnitine-on-hepatitis-c-virus-infection
#12
Yoko Tsukuda, Goki Suda, Seiji Tsunematsu, Jun Ito, Fumiyuki Sato, Katsumi Terashita, Masato Nakai, Takuya Sho, Osamu Maehara, Tomoe Shimazaki, Megumi Kimura, Kenichi Morikawa, Mitsuteru Natsuizaka, Koji Ogawa, Shunsuke Ohnishi, Makoto Chuma, Naoya Sakamoto
Hepatitis C virus (HCV) has been reported to hijack fatty acid metabolism in infected hepatocytes, taking advantage of lipid droplets for virus assembly. In this study, we analyzed the anti-HCV activity of l-carnitine, a substance involved in the transport of fatty acids into mitochondria. JFH-1 or HCV replicon-transfected Huh7.5.1 cells were treated with or without l-carnitine to examine its anti-HCV effects. The effects of l-carnitine on HCV entry, HCV-induced adipogenesis and lipid droplet formation, and HCV-induced oxidative stress were examined...
September 24, 2016: Journal of Medical Virology
https://www.readbyqxmd.com/read/27661118/small-heterodimer-partner-1-directly-interacts-with-ns5a-viral-protein-and-has-a-key-role-in-hcv-related-liver-cell-transformation
#13
Beatrice Conti, Cristiana Porcu, Carmela Viscomi, Antonella Minutolo, Susan Costantini, Marco Corazzari, Gino Iannucci, Barbara Barbaro, Clara Balsano
HCV life cycle is strictly correlated with the hepatocyte lipid metabolism; moreover, the progression of HCV chronic hepatitis is accelerated by the presence of liver steatosis. Among the steatogenic genes deregulated during the HCV infection one of the most attractive is the Small Heterodimer Protein 1 (SHP1; NR0B2), that is involved in a remarkable number of metabolic functions. HCV NS5A is an essential and integral component of the HCV membranous-web replicon complex (RC) and plays an essential role to transfer the viral genome from the RCs to the surface of the lipid droplets (LDs) that, in turn, play a key function during HCV life cycle...
September 20, 2016: Oncotarget
https://www.readbyqxmd.com/read/27645237/anti-viral-nucleotide-incorporation-by-recombinant-human-mitochondrial-rna-polymerase-is-predictive-for-increased-in-vivo-mitochondrial-toxicity-risk
#14
Martijn Fenaux, Xiaodong Lin, Fumiaki Yokokawa, Zachary Sweeney, Oliver Saunders, Lili Xie, Siew Pheng Lim, Marianne Uteng, Kyoko Uehara, Robert Warne, Wang Gang, Christopher Jones, Satya Yendluri, Helen Gu, Keith Mansfield, Julie Boisclair, Tycho Heimbach, Alexandre Catoire, Kathryn Bracken, Margaret Weaver, Heinz Moser, Weidong Zhong
Nucleoside or nucleotide inhibitors are a highly successful class of antivirals due to selectivity, potency, broad coverage, and high barrier to resistance. Nucleosides are the backbone of combination treatments for HIV, hepatitis B and - since the FDA approval of sofosbuvir in 2013 - also for hepatitis C (HCV). However, many promising nucleotides have advanced to clinical trials only to be terminated due to unexpected toxicity. Here we describe the in vitro pharmacology of 1: , a monophosphate prodrug of a 2' -ethynyluridine developed for the treatment of HCV...
September 19, 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27609828/extracellular-lipid-free-apolipoprotein-e-inhibits-hcv-replication-and-induces-abcg1-dependent-cholesterol-efflux
#15
Emilie Crouchet, Mathieu Lefèvre, Eloi R Verrier, Marine A Oudot, Thomas F Baumert, Catherine Schuster
OBJECTIVE: The HCV life cycle and the lipid metabolism are inextricably intertwined. In the blood, HCV virions are associated with lipoproteins, forming lipoviroparticles (LVPs), which are the most infectious form of the virus. Apolipoprotein E (apoE), a key LVP component, plays an essential role in HCV entry, assembly and egress. ApoE is also a cell host factor involved in lipoprotein homeostasis. Although the majority of apoE is associated with lipoproteins, a lipid-free (LF) form exists in blood...
September 8, 2016: Gut
https://www.readbyqxmd.com/read/27591428/mir-148a-and-mir-30a-limit-hcv-dependent-suppression-of-the-lipid-droplet-protein-adrp-in-hcv-infected-cell-models
#16
Nada M El-Ekiaby, Radwa Y Mekky, Sarah E Riad, Dalia S Elhelw, Mohammed El-Sayed, Gamal Esmat, Ahmed I Abdelaziz
OBJECTIVES: Hepatitis C Virus (HCV) promotes lipid droplet (LD) formation and perturbs the expression of the LD associated PAT proteins ADRP and TIP47, to promote its own lifecycle. HCV enhances TIP47 and suppresses ADRP by displacing it from LD surface in infected cell models. We have previously shown that suppression of TIP47 by miR-148a and miR-30a decreased intracellular LDs and HCV RNA. Thus, this study aimed at examining whether this microRNA-mediated suppression of HCV would limit HCV-dependent displacement of ADRP from LDs...
September 3, 2016: Journal of Medical Virology
https://www.readbyqxmd.com/read/27585283/functions-and-malfunctions-of-mammalian-dna-cytosine-deaminases
#17
Sachini U Siriwardena, Kang Chen, Ashok S Bhagwat
The AID/APOBEC family enzymes convert cytosines in single-stranded DNA to uracils, causing base substitutions and strand breaks. They are induced by cytokines produced during the body's inflammatory response to infections, and they help combat infections through diverse mechanisms. AID is essential for the maturation of antibodies and causes mutations and deletions in antibody genes through somatic hypermutation (SHM) and class-switch recombination (CSR) processes. One member of the APOBEC family, APOBEC1, edits mRNA for a protein involved in lipid transport...
September 1, 2016: Chemical Reviews
https://www.readbyqxmd.com/read/27582510/lysophosphatidylcholine-acyltransferase-1-is-downregulated-by-hepatitis-c-virus-impact-on-production-of-lipo-viro-particles
#18
Frauke Beilstein, Matthieu Lemasson, Véronique Pène, Dominique Rainteau, Sylvie Demignot, Arielle R Rosenberg
OBJECTIVE: HCV is intimately linked with the liver lipid metabolism, devoted to the efflux of triacylglycerols stored in lipid droplets (LDs) in the form of triacylglycerol-rich very-low-density lipoproteins (VLDLs): (i) the most infectious HCV particles are those of lowest density due to association with triacylglycerol-rich lipoproteins and (ii) HCV-infected patients frequently develop hepatic steatosis (increased triacylglycerol storage). The recent identification of lysophosphatidylcholine acyltransferase 1 (LPCAT1) as an LD phospholipid-remodelling enzyme prompted us to investigate its role in liver lipid metabolism and HCV infectious cycle...
August 31, 2016: Gut
https://www.readbyqxmd.com/read/27563366/exploratory-analysis-for-the-evaluation-of-estimated-glomerular-filtration-rate-cholesterol-and-triglycerides-after-switching-from-tenofovir-emtricitabine-plus-atazanavir-ritonavir-atv-r-to-abacavir-lamivudine-plus-atv-r-in-patients-with-preserved-renal-function
#19
Maria Concetta Postorino, Eugenia Quiros-Roldan, Franco Maggiolo, Simona Di Giambenedetto, Nicoletta Ladisa, Giuseppe Lapadula, Silvia Lorenzotti, Laura Sighinolfi, Filippo Castelnuovo, Massimo Di Pietro, Daria Gotti, Nicola Mazzini, Carlo Torti
BACKGROUND AND OBJECTIVES: Renal toxicity due to tenofovir (TDF) has been largely described in patients with HIV infection. However, other antiretroviral drugs (such as atazanavir [ATV], especially when boosted by ritonavir, ATV/r) could perpetuate some degrees of renal impairment with or without TDF co-administration. Also, possible benefits of stopping TDF in patients without renal diseases is not well known. This study aimed at exploring evolution of renal function and lipid profile after switching from tenofovir/emtricitabine (TDF/FTC) to abacavir/lamivudine (ABC/3TC), maintaining the ATV/r component of the regimen...
2016: Open AIDS Journal
https://www.readbyqxmd.com/read/27550144/adp-ribosylation-factor-related-protein-1-interacts-with-ns5a-and-regulates-hepatitis-c-virus-propagation
#20
Yun-Sook Lim, Huong T T Ngo, Jihye Lee, Kidong Son, Eun-Mee Park, Soon B Hwang
The life cycle of hepatitis C virus (HCV) is tightly coupled to the lipid metabolism of host cells. In order to identify host factors involved in HCV propagation, we have previously screened a small interfering RNA (siRNA) library targeting host genes that control lipid metabolism and lipid droplet (LD) formation using cell culture-grown HCV (HCVcc)-infected cells. In this study, we selected and characterized the gene encoding ADP-ribosylation factor-related protein 1 (ARFRP1). ARFRP1 is essential for LD growth and is involved in the regulation of lipolysis...
2016: Scientific Reports
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