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https://www.readbyqxmd.com/read/28883690/direct-acting-antiviral-agents-against-hepatitis-c-virus-and-lipid-metabolism
#1
EDITORIAL
Tatsuo Kanda, Mitsuhiko Moriyama
Hepatitis C virus (HCV) infection induces steatosis and is accompanied by multiple metabolic alterations including hyperuricemia, reversible hypocholesterolemia and insulin resistance. Total cholesterol, low-density lipoprotein-cholesterol and triglyceride levels are increased by peginterferon and ribavirin combination therapy when a sustained virologic response (SVR) is achieved in patients with HCV. Steatosis is significantly more common in patients with HCV genotype 3 but interferon-free regimens are not always effective for treating HCV genotype 3 infections...
August 21, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28864162/treatment-induced-viral-cure-of-hepatitis-c-virus-infected-patients-involves-a-dynamic-interplay-among-three-important-molecular-players-in-lipid-homeostasis-circulating-microrna-mir-24-mir-223-and-proprotein-convertase-subtilisin-kexin-type-9
#2
Anastasia Hyrina, Andrea D Olmstead, Paul Steven, Mel Krajden, Edward Tam, François Jean
In patients with chronic hepatitis C virus (HCV) infection, viral hijacking of the host-cell biosynthetic pathways is associated with altered lipid metabolism, which contributes to disease progression and may influence antiviral response. We investigated the molecular interplay among four key regulators of lipid homeostasis [microRNA (miR)-122, miR-24, miR-223, and proprotein convertase subtilisin/kexin type 9 (PCSK9)] in HCV-infected patients (n=72) who achieved a treatment-based viral cure after interferon-based therapy with first-generation direct-acting antivirals...
September 2017: EBioMedicine
https://www.readbyqxmd.com/read/28862649/immune-evasion-strategies-during-chronic-hepatitis-b-and-c-virus-infection
#3
REVIEW
Ana Maria Ortega-Prieto, Marcus Dorner
Both hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are a major global healthcare problem with more than 240 million and 70 million infected, respectively. Both viruses persist within the liver and result in progressive liver disease, resulting in liver fibrosis, cirrhosis and hepatocellular carcinoma. Strikingly, this pathogenesis is largely driven by immune responses, unable to clear an established infection, rather than by the viral pathogens themselves. Even though disease progression is very similar in both infections, HBV and HCV have evolved distinct mechanisms, by which they ensure persistence within the host...
September 1, 2017: Vaccines
https://www.readbyqxmd.com/read/28834042/changes-in-serum-lipid-profiles-caused-by-three-regimens-of-interferon-free-direct-acting-antivirals-for-patients-infected-with-hepatitis-c-virus
#4
Takako Inoue, Takaaki Goto, Etsuko Iio, Kayoko Matsunami, Kei Fujiwara, Noboru Shinkai, Kentaro Matsuura, Takeshi Matsui, Shunsuke Nojiri, Yasuhito Tanaka
AIM: As described previously, serum low-density lipoprotein cholesterol (LDL-C) increases during treatment of chronic hepatitis C (CHC) with interferon-free direct-acting antivirals (DAAs). We sought to compare the changes of serum lipid profiles caused by three regimens. METHODS: A total of 216 CHC patients were enrolled. Among 170 patients infected with HCV genotype 1b, 85 received daclatasvir plus asunaprevir (DCV/ASV) and 85 received sofosbuvir plus ledipasvir (SOF/LDV)...
August 19, 2017: Hepatology Research: the Official Journal of the Japan Society of Hepatology
https://www.readbyqxmd.com/read/28820612/the-potential-of-signal-peptide-peptidase-as-a-therapeutic-target-for-hepatitis-c
#5
REVIEW
Kohji Moriishi
Chronic infection with hepatitis C virus (HCV) causes liver steatosis, cirrhosis, metabolic syndrome with inflammation, and eventually leads to hepatocellular carcinoma. HCV core protein is a well-known capsid protein and pathogenic factor related to lipid accumulation, type 2 diabetes mellitus, and carcinogenesis. Cleavage of the C-terminal transmembrane region by signal peptide peptidase (SPP) is required for maturation of the core protein. Areas covered: Herein, this review details the general aspects of the structure, lifecycle, pathogenesis, and maturation of the HCV core protein, the function of SPP, and clinically available direct-acting antivirals (DAAs)...
September 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/28815532/hepatitis-c-virus-replication
#6
Tetsuro Suzuki
Viruses use synthetic mechanism and organelles of the host cells to facilitate their replication and make new viruses. Host's ATP provides necessary energy. Hepatitis C virus (HCV) is a major cause of liver disease. Like other positive-strand RNA viruses, the HCV genome is thought to be synthesized by the replication complex, which consists of viral- and host cell-derived factors, in tight association with structurally rearranged vesicle-like cytoplasmic membranes. The virus-induced remodeling of subcellular membranes, which protect the viral RNA from nucleases in the cytoplasm, promotes efficient replication of HCV genome...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28791972/hcv-co-infection-is-associated-with-metabolic-abnormalities-among-haart-naive-hiv-infected-persons
#7
M A Kuti, J O Akinyemi, B O Ogunbosi, K M Kuti, O A Adesina, O A Awolude, O S Michael, I F Adewole
OBJECTIVES: To determine the metabolic abnormalities among Hepatitis C Virus (HCV) co infected HAART naïve HIV infected persons within the adult ARV clinic of the University College Hospital/University of Ibadan, Ibadan, Nigeria Methods: This was a retrospective study involving the review of clinical records of newly recruited HIV-infected persons in the adult antiretroviral (ARV) clinic over a 12 month period (January - December 2006). Baseline results for fasting plasma glucose (FPG) and fasting lipid profile were retrieved...
July 2017: Nigerian Journal of Clinical Practice
https://www.readbyqxmd.com/read/28780227/insights-into-the-immune-manipulation-mechanisms-of-pollen-allergens-by-protein-domain-profiling
#8
Seema Patel, Aruna Rani, Arun Goyal
Plant pollens are airborne allergens, as their inhalation causes immune activation, leading to rhinitis, conjunctivitis, sinusitis and oral allergy syndrome. A myriad of pollen proteins belonging to profilin, expansin, polygalacturonase, glucan endoglucosidase, pectin esterase, and lipid transfer protein class have been identified. In the present in silico study, the protein domains of fifteen pollen sequences were extracted from the UniProt database and submitted to the interactive web tool SMART (Simple Modular Architecture Research Tool), for finding the protein domain profiles...
July 29, 2017: Computational Biology and Chemistry
https://www.readbyqxmd.com/read/28747506/hcv-induces-the-localization-of-lipid-rafts-to-autophagosomes-for-its-rna-replication
#9
Ja Yeon Kim, Linya Wang, Jiyoung Lee, Jing-Hsiung James Ou
Autophagy plays important roles in maintaining cellular homeostasis. It uses double- or multiple- membrane vesicles termed autophagosomes to remove protein aggregates and damaged organelles from the cytoplasm for recycling. Hepatitis C virus (HCV) has been shown to induce autophagy to enhance its own replication. Here we describe a procedure that combines membrane flotation and affinity chromatography for the purification of autophagosomes from cells that harbor a HCV subgenomic RNA replicon. The purified autophagosomes had double- or multiple- membrane structures with a diameter ranging from 200 nm to 600 nm...
July 26, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28729862/rad51-interacts-with-non-structural-3-protein-of-hepatitis-c-virus-and-regulates-viral-production
#10
Kidong Son, Tram T T Nguyen, Jae-Woong Choi, Long V Pham, Trang T D Luong, Yun-Sook Lim, Soon B Hwang
Hepatitis C virus (HCV) is a leading cause of chronic liver disease affecting over 170 million people worldwide. Chronic infection with HCV progresses to liver fibrosis, cirrhosis, and hepatocellular carcinoma. HCV exploits host cellular factors for viral propagation. To investigate the cellular factors required for HCV propagation, we screened a siRNA library targeting human cell cycle genes using cell culture grown HCV-infected cells. In the present study, we selected and characterized a gene encoding Rad51...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28724915/quinolinate-phosphoribosyltransferase-is-an-antiviral-host-factor-against-hepatitis-c-virus-infection
#11
Zhilong Wang, Yanhang Gao, Chao Zhang, Haiming Hu, Dongwei Guo, Yi Xu, Qiuping Xu, Weihong Zhang, Sisi Deng, Pingyun Lv, Yan Yang, Yanhua Ding, Qingquan Li, Changjiang Weng, Xinwen Chen, Sitang Gong, Hairong Chen, Junqi Niu, Hong Tang
HCV infection can decrease NAD(+)/NADH ratio, which could convert lipid metabolism to favor HCV replication. In hepatocytes, quinolinate phosphoribosyl transferase (QPRT) catabolizes quinolinic acid (QA) to nicotinic acid mononucleotide (NAMN) for de novo NAD synthesis. However, whether and how HCV modulates QPRT hence the lipogenesis is unknown. In this work, we found QPRT was reduced significantly in livers of patients or humanized C/O(Tg) mice with persistent HCV infection. Mechanistic studies indicated that HCV NS3/4A promoted proteasomal degradation of QPRT through Smurf2, an E3 ubiquitin-protein ligase, in Huh7...
July 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28722331/hepatitis-c-virus-and-proprotein-convertase-subtilisin-kexin-type-9-a-detrimental-interaction-to-increase-viral-infectivity-and-disrupt-lipid-metabolism
#12
REVIEW
Matteo Pirro, Vanessa Bianconi, Daniela Francisci, Elisabetta Schiaroli, Francesco Bagaglia, Amirhossein Sahebkar, Franco Baldelli
From viral binding to the hepatocyte surface to extracellular virion release, the replication cycle of the hepatitis C virus (HCV) intersects at various levels with lipid metabolism; this leads to a derangement of the lipid profile and to increased viral infectivity. Accumulating evidence supports the crucial regulatory role of proprotein convertase subtilisin/kexin type 9 (PCSK9) in lipoprotein metabolism. Notably, a complex interaction between HCV and PCSK9 has been documented. Indeed, either increased or reduced circulating PCSK9 levels have been observed in HCV patients; this discrepancy might be related to several confounders, including HCV genotype, human immunodeficiency virus (HIV) coinfection and the ambiguous HCV-mediated influence on PCSK9 transcription factors...
July 18, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28721844/cd81-large-extracellular-loop-containing-fusion-proteins-with-a-dominant-negative-effect-on-hcv-cell-spread-and-replication
#13
Boyan Grigorov, Jennifer Molle, Eric Rubinstein, Fabien Zoulim, Birke Bartosch
The roles of CD81 in the hepatitis C virus (HCV) life cycle are multiple but remain ill characterized. CD81 is known to interact with the HCV glycoproteins as an attachment factor. It also has an important role in the post-attachment entry process. Its interaction with claudin-1, for example, is vital for viral uptake and trafficking. Furthermore, CD81 and its role in membrane organization and trafficking are thought to play a pivotal role in HCV replication. Some of these functions are particularly limited to human CD81; others can be substituted with CD81 molecules from other species...
July 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28715065/hypertension-dyslipidemia-and-cardiovascular-risk-in-hiv-infected-adults-in-poland
#14
Magdalena Rogalska-Płońska, Paweł Rogalski, Magdalena Leszczyszyn-Pynka, Justyna Stempkowska, Piotr Kocbach, Aldona Kowalczuk-Kot, Małgorzata Janczarek, Anna Grzeszczuk
BACKGROUND: Prevalence of cardiovascular diseases (CVD) in HIV infected patients increases with aging and duration of the disease. Hypertension (HA), high cholesterol level obesity, diabetes, tobacco exposure and use of alcohol are among the traditional risk factors that contribute to CVD. AIM: was to determinate the incidence of HA, lipid disturbances and CVD risk in dependence on clinical, viral and biochemical factors. METHODS: Four hundred and seventeen HIV infected Caucasian adult patients from the four clinical centers in Poland were enrolled and analyzed on the basis of available medical data from the years 2013-2015...
July 17, 2017: Kardiologia Polska
https://www.readbyqxmd.com/read/28709434/integrating-multi-omics-analyses-of-nonomuraea-dietziae-to-reveal-the-role-of-soybean-oil-in-4-oh-meleu-4-csa-overproduction
#15
Huanhuan Liu, Di Huang, Lina Jin, Cheng Wang, Shaoxiong Liang, Jianping Wen
BACKGROUND: Nonomuraea dietziae is a promising microorganism to mediate the region-specific monooxygenation reaction of cyclosporine A (CsA). The main product [(4'-OH)MeLeu](4)-CsA possesses high anti-HIV/HCV and hair growth-stimulating activities while avoiding the immunosuppressive effect of CsA. However, the low conversion efficiency restricts the clinical application. In this study, the production of [(4'-OH)MeLeu](4)-CsA was greatly improved by 55.6% from 182.8 to 284.4 mg/L when supplementing soybean oil into the production medium, which represented the highest production of [(4'-OH)MeLeu](4)-CsA so far...
July 14, 2017: Microbial Cell Factories
https://www.readbyqxmd.com/read/28689587/metabolic-manifestations-of-hepatitis-c-virus-diabetes-mellitus-dyslipidemia
#16
REVIEW
Lawrence Serfaty
Metabolic disorders are common in patients with chronic hepatitis C virus (HCV) infection. Epidemiologic and clinical data indicate an overprevalence of lipids abnormalite, steatosis, insuline resistance (IR) and diabetes mellitus in HCV patients, suggesting that HCV itself may interact with glucido-lipidic metabolism. HCV interacts with the host lipid metabolism by several mechanisms leading to hepatic steatosis and hypolipidemia which are reversible after viral eradication. Liver and peripheral IR are HCV genotype/viral load dependent and improved after viral eradication...
August 2017: Clinics in Liver Disease
https://www.readbyqxmd.com/read/28687362/the-unexpected-function-of-a-highly-conserved-yxx%C3%AE-motif-in-hcv-core-protein
#17
Eirini Karamichali, Elisavet Serti, Aikaterini Gianneli, Aikaterini Papaefthymiou, Athanassios Kakkanas, Pelagia Foka, Alexandros Seremetakis, Konstantina Katsarou, Ioannis P Trougakos, Urania Georgopoulou
Hepatitis C virus (HCV) is an RNA positive strand virus, member of the Flaviviridae family. The HCV viral particle is composed of a capsid containing the genome, surrounded by an endoplasmic reticulum (ER)-derived lipid bilayer where E1 and E2 are assembled as heterodimers. However, different forms of viral particles have been identified in the serum of HCV-infected patients, including non-enveloped particles. Previous reports have demonstrated that HCV non-enveloped capsid-like particles (HCVne) can be generated by HCV core protein sequence...
July 5, 2017: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/28671671/wnt-%C3%AE-catenin-activation-and-macrophage-induction-during-liver-cancer-development-following-steatosis
#18
A Debebe, V Medina, C-Y Chen, I M Mahajan, C Jia, D Fu, L He, N Zeng, B W Stiles, C-L Chen, M Wang, K-R Aggarwal, Z Peng, J Huang, J Chen, M Li, T Dong, S Atkins, Z Borok, W Yuan, K Machida, C Ju, M Kahn, D Johnson, B L Stiles
Obesity confers an independent risk for carcinogenesis. In the liver, steatosis often proceeds cancer formation; however, the mechanisms by which steatosis promotes carcinogenesis is unknown. We hypothesize that steatosis alters the microenvironment to promote proliferation of tumor initiating cells (TICs) and carcinogenesis. We used several liver cancer models to address the mechanisms underlying the role of obesity in cancer and verified these findings in patient populations. Using bioinformatics analysis and verified by biochemical assays, we identified that hepatosteatosis resulting from either Pten deletion or transgenic expression of HCV core/NS5A proteins, promotes the activation of Wnt/β-catenin...
July 3, 2017: Oncogene
https://www.readbyqxmd.com/read/28657143/emergence-of-drug-resistance-associated-variants-and-changes-in-serum-lipid-profiles-in-sofosbuvir-plus-ledipasvir-treated-chronic-hepatitis-c-patients
#19
Hiromi Kan, Michio Imamura, Yoshiiku Kawakami, Kana Daijo, Yuji Teraoka, Fumi Honda, Yuki Nakamura, Kei Morio, Tomoki Kobayashi, Takashi Nakahara, Yuko Nagaoki, Tomokazu Kawaoka, Masataka Tsuge, Hiroshi Aikata, Clair Nelson Hayes, Daiki Miki, Hidenori Ochi, Yoji Honda, Nami Mori, Shintaro Takaki, Keiji Tsuji, Kazuaki Chayama
Combination of sofosbuvir plus ledipasvir therapy has been expected to enhance sustained virological response (SVR) rates in hepatitis C virus (HCV) genotype 1 chronic infected patients. We analyzed the emergence of drug resistance-associated variants (RAVs) in treatment failure and changes in lipid profiles in sofosbuvir/ledipasvir-treated patients. A total of 176 patients with chronic HCV genotype 1 infection without decompensated liver cirrhosis were treated with sofosbuvir/ledipasvir for 12 weeks. NS5A and NS5B RAVs were determined by either Invader assay or direct sequencing...
June 28, 2017: Journal of Medical Virology
https://www.readbyqxmd.com/read/28630011/interplay-between-hepatitis-c-virus-and-lipid-metabolism-during-virus-entry-and-assembly
#20
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
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