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https://www.readbyqxmd.com/read/28437468/role-of-cleavage-at-the-core-e1-junction-of-hepatitis-c-virus-polyprotein-in-viral-morphogenesis
#1
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
https://www.readbyqxmd.com/read/28428715/impact-of-interferon-free-antivirus-therapy-on-lipid-profiles-in-patients-with-chronic-hepatitis-c-genotype-1b
#2
Daisuke Endo, Kenichi Satoh, Noritomo Shimada, Atsushi Hokari, Yoshio Aizawa
AIM: To investigate the influence of interferon-free antivirus therapy on lipid profiles in chronic hepatitis C virus genotype 1b (HCV1b) infection. METHODS: Interferon-free antiviral agents were used to treat 276 patients with chronic HCV1b infection, and changes in serum lipids of those who achieved sustained virologic response (SVR) were examined. The treatment regimen included 24 wk of daclatasvir plus asunaprevir (DCV + ASV) or 12 wk of sofosbuvir plus ledipasvir (SOF + LDV)...
April 7, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28421422/hepatitis-c-virus-genotype-3-update-on-current-and-emergent-therapeutic-interventions
#3
REVIEW
Steven W Johnson, Dorothea K Thompson, Brianne Raccor
PURPOSE OF REVIEW: Direct-acting antiviral agents (DAAs) have markedly improved the prognosis of hepatitis C virus (HCV)-genotype 3 (GT3), a highly prevalent infection worldwide. However, in patients with hepatic fibrosis, cirrhosis, or hepatocellular carcinoma (HCC), GT3 infection presents a treatment challenge compared with other genotypes. The dependence of the HCV life cycle on host lipid metabolism suggests the possible utility of targeting host cellular factors for combination anti-HCV therapy...
June 2017: Current Infectious Disease Reports
https://www.readbyqxmd.com/read/28373999/data-on-the-effects-of-low-iron-diet-on-serum-lipid-profile-in-hcv-transgenic-mouse-model
#4
Alice Conigliaro, Viviana Costa, Rosario Amato, Carmine Mancone
Here, we presented new original data on the effects of iron depletion on the circulating lipid profile in B6HCV mice, a murine model of HCV-related dyslipidemia. Male adult B6HCV mice were subjected to non-invasive iron depletion by low iron diet. Serum iron concentration was assessed for evaluating the effects of the dietary iron depletion. Concentrations of circulating triglycerides, total cholesterol, Low Density Lipoproteins (LDLs), High Density Lipoproteins (HDLs) were analyzed and reported by using stacked line charts...
June 2017: Data in Brief
https://www.readbyqxmd.com/read/28336330/requirement-of-cytosolic-phospholipase-a2-gamma-in-lipid-droplet-formation
#5
Xi Su, Shuhui Liu, Xianwen Zhang, Sin Man Lam, Xue Hu, Yuan Zhou, Jizheng Chen, Yun Wang, Chunchen Wu, Guanghou Shui, Mengji Lu, Rongjuan Pei, Xinwen Chen
Lipid droplet (LD) accumulation in hepatocytes is a typical character of steatosis. Hepatitis C virus (HCV) infection, one of the risk factors related to steatosis, induced LD accumulation in cultured cells. However, the mechanisms of which HCV induce LD formation are not fully revealed. Previously we identified cytosolic phospholipase A2 gamma (PLA2G4C) as a host factor upregulated by HCV infection and involved in HCV replication. Here we further revealed that PLA2G4C plays an important role in LD biogenesis and refined the functional analysis of PLA2G4C in LD biogenesis and HCV assembly...
March 20, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28249699/detection-of-high-biliary-and-fecal-viral-loads-in-patients-with-chronic-hepatitis-c-virus-infection
#6
Hugo Monrroy, Jenniffer Angulo, Karla Pino, Pilar Labbé, Juan Francisco Miquel, Marcelo López-Lastra, Alejandro Soza
BACKGROUND: The life cycle of the hepatitis C virus (HCV) is closely associated with lipid metabolism. Recently, NPC1L1 (a cholesterol transporter) has been reported to function as an HCV receptor. This receptor is expressed in the hepatocyte canalicular membrane and in the intestine; serving as a key transporter for the cholesterol enterohepatic cycle. OBJECTIVES: We hypothesized that HCV might have a similar cycle, so we aimed to study the presence of HCV in bile and stools of infected patients...
February 26, 2017: Gastroenterología y Hepatología
https://www.readbyqxmd.com/read/28223719/hepatitis-c-virus-associated-pruritus-etiopathogenesis-and-therapeutic-strategies
#7
EDITORIAL
Youssef Alhmada, Denis Selimovic, Fadi Murad, Sarah-Lilly Hassan, Youssef Haikel, Mossaad Megahed, Matthias Hannig, Mohamed Hassan
In addition to its contributing role in the development of chronic liver diseases, chronic hepatitis C virus (HCV) infection is associated with extrahepatic manifestations, particularly, cutaneous-based disorders including those with pruritus as a symptom. Pruritus is frequently associated with the development of chronic liver diseases such as cholestasis and chronic viral infection, and the accumulation of bile acids in patients' sera and tissues as a consequence of liver damage is considered the main cause of pruritus...
February 7, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28218651/proteome-characteristics-of-non-alcoholic-steatohepatitis-liver-tissue-and-associated-hepatocellular-carcinomas
#8
Anna Kakehashi, Vasily E Stefanov, Naomi Ishii, Takahiro Okuno, Hideki Fujii, Kazuaki Kawai, Norifumi Kawada, Hideki Wanibuchi
To uncover mechanisms of nonalcoholic steatohepatitis (NASH) associated hepatocarcinogenesis, we compared the proteomes of human NASH-associated liver biopsies, resected hepatocellular carcinomas (HCCs) and HCCs of HCV⁺ patients with normal liver tissue of patients with gastrointestinal tumor metastasis, in formalin-fixed paraffin-embedded samples obtained after surgery in our hospital during the period from 2006 to 2011. In addition, proteome analysis of liver tumors in male STAM NASH-model mice was performed...
February 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28211910/link-between-plasminogen-activator-inhibitor-1-and-cardiovascular-risk-in-chronic-hepatitis-c-after-viral-clearance
#9
Ming-Ling Chang, Yu-Sheng Lin, Li-Heng Pao, Hsin-Chih Huang, Cheng-Tang Chiu
The pathophysiological implications of plasminogen activator inhibitor-1 (PAI-1) in HCV infection remain obscure. This prospective study evaluated 669 HCV patients, of whom 536 had completed a course of anti-HCV therapy and had pre-, peri- and post-therapy measurements of various profiles, including PAI-1 levels. Multivariate analysis demonstrated, before anti-HCV-therapy, platelet count and PAI-1-rs1799889 genotype were associated with PAI-1 levels. Among patients with a sustained virological response (SVR, n = 445), platelet count was associated with PAI-1 level at 24 weeks post-therapy...
February 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28193659/oligonucleotide-lipid-conjugates-forming-g-quadruplex-structures-are-potent-and-pangenotypic-hepatitis-c-virus-entry-inhibitors-in-vitro-and-ex-vivo
#10
George Koutsoudakis, Alexia Paris de León, Carolina Herrera, Marcus Dorner, Gemma Pérez-Vilaró, Sébastien Lyonnais, Santiago Grijalvo, Ramon Eritja, Andreas Meyerhans, Gilles Mirambeau, Juana Díez
An HCV epidemic affecting HIV-infected men who have sex with men (MSM) is expanding worldwide. Albeit the improved cure rates obtained with the new direct-acting antiviral drug (DAA) combinations, the high rate of reinfection within this population calls urgently for novel preventive interventions. Here we show in cell culture and ex vivo experiments with human colorectal tissue that lipoquads, G-quadruplex DNA structures fused to cholesterol, are efficient HCV pangenotypic entry and cell-to-cell transmission inhibitors...
February 13, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28152568/apolipoprotein-a-inhibits-hepatitis-c-virus-entry-through-interaction-with-infectious-particles
#11
Catarina Oliveira, Carole Fournier, Véronique Descamps, Virginie Morel, Corey A Scipione, Rocco Romagnuolo, Marlys L Koschinsky, Agnès Boullier, Paulo Marcelo, Jean-Marc Domon, Etienne Brochot, Gilles Duverlie, Catherine Francois, Sandrine Castelain, Francois Helle
The development of different cell culture models has greatly contributed to improve the knowledge of the hepatitis C virus (HCV) life cycle. However, it is still challenging to grow HCV clinical isolates in cell culture. This would open new perspectives to study HCV biology, including drug resistant variants emerging with new antiviral therapies. In this study we hypothesized that this hurdle could be due to the presence of inhibitory factors in patient serum. Combining polyethylene glycol precipitation, iodixanol gradient and size-exclusion chromatography, we obtained a purified fraction enriched in inhibitory factors from HCV seronegative sera...
February 2, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28148799/computational-prediction-of-the-heterodimeric-and-higher-order-structure-of-gpe1-gpe2-envelope-glycoproteins-encoded-by-hepatitis-c-virus
#12
Holly Freedman, Michael R Logan, Darren Hockman, Julia Koehler Leman, John Lok Man Law, Michael Houghton
Despite the recent success of newly developed direct-acting antivirals against hepatitis C, the disease continues to be a global health threat due to the lack of diagnosis of most carriers and the high cost of treatment. The heterodimer formed by glycoproteins E1 and E2 within the hepatitis C virus (HCV) lipid envelope is a potential vaccine candidate and antiviral target. While the structure of E1/E2 has not yet been resolved, partial crystal structures of the E1 and E2 ectodomains have been determined. The unresolved parts of the structure are within the realm of what can be modeled with current computational modeling tools...
April 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28128295/rna-helicase-ddx3-maintains-lipid-homeostasis-through-upregulation-of-the-microsomal-triglyceride-transfer-protein-by-interacting-with-hnf4-and-shp
#13
Tsung-Yuan Tsai, Wei-Ting Wang, Hao-Kang Li, Wei-Ju Chen, Yu-Hong Tsai, Chi-Hong Chao, Yan-Hwa Wu Lee
Multifunctional RNA helicase DDX3 participates in HCV infection, one of the major causes of hepatic steatosis. Here, we investigated the role of DDX3 in hepatic lipid metabolism. We found that HCV infection severely reduced DDX3 expression. Analysis of intracellular triglyceride and secreted ApoB indicated that lipid accumulations were increased while ApoB secretion were decreased in DDX3 knockdown HuH7 and HepG2 cell lines. Down-regulation of DDX3 significantly decreased protein and transcript expression of microsomal triglyceride transfer protein (MTP), a key regulator of liver lipid homeostasis...
January 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28126468/autotaxin-lysophosphatidic-acid-receptor-signalling-regulates-hepatitis-c-virus-replication
#14
Michelle J Farquhar, Isla S Humphreys, Simon A Rudge, Garrick K Wilson, Bishnupriya Bhattacharya, Maria Ciaccia, Ke Hu, Qifeng Zhang, Laurent Mailly, Gary M Reynolds, Margaret Ashcroft, Peter Balfe, Thomas F Baumert, Stephanie Roessler, Michael J O Wakelam, Jane A McKeating
BACKGROUND & AIMS: Chronic hepatitis C is a global health problem with an estimated 170 million hepatitis C virus (HCV) infected individuals at risk of progressive liver disease and hepatocellular carcinoma (HCC). Autotaxin (ATX, gene name: ENPP2) is a phospholipase with diverse roles in the physiological and pathological processes including inflammation and oncogenesis. Clinical studies have reported increased ATX expression in chronic hepatitis C, however, the pathways regulating ATX and its role in the viral life cycle are not well understood...
January 23, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28105255/pi3k-ship2-pten-pathway-in-cell-polarity-and-hepatitis-c-virus-pathogenesis
#15
REVIEW
Aline Awad, Ama Gassama-Diagne
Hepatitis C virus (HCV) infects hepatocytes, polarized cells in the liver. Chronic HCV infection often leads to steatosis, fibrosis, cirrhosis and hepatocellular carcinoma, and it has been identified as the leading cause of liver transplantation worldwide. The HCV replication cycle is dependent on lipid metabolism and particularly an accumulation of lipid droplets in host cells. Phosphoinositides (PIs) are minor phospholipids enriched in different membranes and their levels are tightly regulated by specific PI kinases and phosphatases...
January 8, 2017: World Journal of Hepatology
https://www.readbyqxmd.com/read/28097097/mir-29a-promotes-lipid-droplet-and-triglyceride-formation-in-hcv-infection-by-inducing-expression-of-srebp-1c-and-cav1
#16
Mennatallah Mamdouh Mahdy, Nada Magdy El-Ekiaby, Rana Mahmoud Hashish, Radwa Ayman Salah, Rasha Sayed Hanafi, Hassan Mohamed Azzazy, Ahmed Ihab Abdelaziz
Aims: To examine the regulation of SREBP-1c and CAV1 by microRNA-29a (miR-29a) in cells infected with hepatitis C virus (HCV) in an attempt to control HCV-induced non-alcoholic fatty liver disease. Methods: In order to examine the manipulation of SREBP-1c and CAV1 by miR-29a, oleic acid (OA)-treated JFH-I-infected Huh-7 cells were used. OA was added 24 h post-transfection and gene expression was investigated by qRT-PCR at 48 h post treatment. The functional impact of the observed alteration in SREBP-1c and CAV1 expression was analyzed by examining lipid droplet (LD) and triglyceride (TG) content at 72 h post-OA treatment using light microscopy and spectrophotometry, respectively...
December 28, 2016: Journal of Clinical and Translational Hepatology
https://www.readbyqxmd.com/read/28073421/-research-advances-in-the-role-of-sphingolipids-in-hcv-and-hbv-life-cycles
#17
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/28053108/a-point-mutation-in-the-n-terminal-amphipathic-helix-%C3%AE-0-in-ns3-promotes-hepatitis-c-virus-assembly-by-altering-core-localization-to-the-endoplasmic-reticulum-and-facilitating-virus-budding
#18
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 (designated helix α0), which is 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, in which all reported adaptive mutations enhancing virion assembly reside...
March 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28050236/hepatitis-c-eradication-with-sofosbuvir-leads-to-significant-metabolic-changes
#19
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/green-fluorescent-protein-tagged-apolipoprotein-e-a-useful-marker-for-the-study-of-hepatic-lipoprotein-egress
#20
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...
March 2017: Traffic
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