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Hepatitis C virus lipids

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https://www.readbyqxmd.com/read/29162867/broad-spectrum-antiviral-agents-secreted-phospholipase-a2-targets-viral-envelope-lipid-bilayers-derived-from-the-endoplasmic-reticulum-membrane
#1
Ming Chen, Chie Aoki-Utsubo, Masanori Kameoka, Lin Deng, Yutaka Terada, Wataru Kamitani, Kei Sato, Yoshio Koyanagi, Makoto Hijikata, Keiko Shindo, Takeshi Noda, Michinori Kohara, Hak Hotta
Hepatitis C virus (HCV), dengue virus (DENV) and Japanese encephalitis virus (JEV) belong to the family Flaviviridae. Their viral particles have the envelope composed of viral proteins and a lipid bilayer acquired from budding through the endoplasmic reticulum (ER). The phospholipid content of the ER membrane differs from that of the plasma membrane (PM). The phospholipase A2 (PLA2) superfamily consists of a large number of members that specifically catalyse the hydrolysis of phospholipids at a particular position...
November 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29161418/no-improvement-in-hemoglobin-a1c-following-hepatitis-c-viral-clearance-in-patients-with-and-without-hiv
#2
Chloe S Chaudhury, Julia Sheehan, Cheryl Chairez, Elizabeth Akoth, Chloe Gross, Rachel Silk, Sarah Kattakuzhy, Elana Rosenthal, Shyam Kottilil, Henry Masur, Colleen Hadigan
Hepatitis C clearance with directly acting antivirals (DAAs) may be associated with acute decreases in hemoglobin A1c (HbA1c). We prospectively evaluated 251 chronic hepatitis C virus (HCV)-infected subjects (31% human immunodeficiency virus [HIV] positive) pre- and post-DAA therapy (median follow-up 28 months). Changes in HbA1c and glucose were minimal and did not differ by sustained virologic response (SVR), HIV, diabetes, or fibrosis. Following SVR, mean change in HbA1c was -0.022 ± 0.53%; however, total and low-density lipoprotein cholesterol increased significantly...
November 17, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29158401/kinesin-dependent-mechanism-for-controlling-triglyceride-secretion-from-the-liver
#3
Priyanka Rai, Mukesh Kumar, Geetika Sharma, Pradeep Barak, Saumitra Das, Siddhesh S Kamat, Roop Mallik
Despite massive fluctuations in its internal triglyceride content, the liver secretes triglyceride under tight homeostatic control. This buffering function is most visible after fasting, when liver triglyceride increases manyfold but circulating serum triglyceride barely fluctuates. How the liver controls triglyceride secretion is unknown, but is fundamentally important for lipid and energy homeostasis in animals. Here we find an unexpected cellular and molecular mechanism behind such control. We show that kinesin motors are recruited to triglyceride-rich lipid droplets (LDs) in the liver by the GTPase ARF1, which is a key activator of lipolysis...
November 20, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29135056/a-systematic-review-of-the-associations-between-hiv-hcv-coinfection-and-biomarkers-of-cardiovascular-disease
#4
REVIEW
Olatokunbo Osibogun, Oluseye Ogunmoroti, Erin D Michos, Erica S Spatz, Babatunde Olubajo, Khurram Nasir, Wasim Maziak
The incidence of human immunodeficiency virus (HIV) and hepatitis C virus (HCV) coinfection has been increasing with over 10 million people affected globally. The role biomarkers play as predictors of cardiovascular disease (CVD) risk among coinfected individuals is not well defined. We aimed to systematically review current evidence describing CVD biomarkers among individuals with HIV/HCV coinfection. We searched EMBASE, CINAHL, Google Scholar, PubMed, and Web of Science from inception to June 2017. MeSH terms and keywords were used to identify studies with information on HIV/HCV coinfection and CVD biomarkers (structural, functional, and serological) such as carotid intima-media thickness (CIMT), endothelial markers, C-reactive protein (CRP), homocysteine, and lipids...
November 14, 2017: Reviews in Medical Virology
https://www.readbyqxmd.com/read/29133317/association-between-visceral-obesity-and-hepatitis-c-infection-stratified-by-gender-a-cross-sectional-study-in-taiwan
#5
Yu-Chung Tsao, Jau-Yuan Chen, Wei-Chung Yeh, Yun-Shing Peng, Wen-Cheng Li
OBJECTIVES: The global prevalence of hepatitis C virus (HCV) is approximately 2%-3%, and the prevalence of the positive anti-HCV antibody has been increasing. Several studies have evaluated regional adipose tissue distribution and metabolism over the past decades. However, no study has focused on the gender difference in visceral obesity among patients with HCV infection. DESIGN: Retrospective cross-sectional study. SETTING: We reviewed the medical records of patients who visited a hospital in Southern Taiwan for health check-up from 2013 to 2015...
November 12, 2017: BMJ Open
https://www.readbyqxmd.com/read/29118118/n-myc-downstream-regulated-gene-1-restricts-hepatitis-c-virus-propagation-by-regulating-lipid-droplet-biogenesis-and-viral-assembly
#6
Cameron J Schweitzer, Fang Zhang, Audrey Boyer, Kristin Valdez, Maggie Cam, T Jake Liang
Host cells harbor various intrinsic mechanisms to restrict viral infections as a first line of antiviral defense. Viruses have evolved various countermeasures against these antiviral mechanisms. Here we show that N-Myc Downstream-Reguated Gene 1 (NDRG1) limits productive HCV infection by inhibiting viral assembly. Interestingly, HCV infection down-regulates NDRG1 protein and mRNA expression. Loss of NDRG1 increases the size and number of lipid droplets, which are the sites of HCV assembly. HCV suppresses NDRG1 expression by up-regulating MYC, which directly inhibits the transcription of NDRG1 Up-regulation of MYC also leads to reduced expression of NDRG1-specific kinase SGK1, resulting in markedly diminished phosphorylation of NDRG1...
November 8, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29104462/association-of-ifnl3-genotype-with-hepatic-steatosis-in-chronic-hepatitis-c-patients-treated-with-peginterferon-and-ribavirin-combination-therapy
#7
Shingo Nakamoto, Fumio Imazeki, Tatsuo Kanda, Shuang Wu, Masato Nakamura, Shin Yasui, Akinobu Tawada, Rintaro Mikata, Tetsuhiro Chiba, Makoto Arai, Osamu Yokosuka, Hiroshi Shirasawa
BACKGROUND: Genetic variation near the interferon lambda 3 (IFNL3) is known to be associated with response to pegylated interferon (pegIFN) and ribavirin combination therapy in patients with chronic hepatitis C virus (HCV) infection which is often accompanied by hepatic steatosis. AIMS: We examined whether this genetic variation is associated with host lipids and treatment response. METHODS: A total of 101 Japanese patients who had underwent liver biopsy before treatment with pegIFN and ribavirin for HCV genotype 1b infection were retrospectively analyzed for association between IFNL3 genotypes (rs8099917) and clinical factors including histopathological features of the liver...
2017: International Journal of Medical Sciences
https://www.readbyqxmd.com/read/29089195/superior-immunogenicity-of-hcv-envelope-glycoproteins-when-adjuvanted-with-cyclic-di-amp-a-sting-activator-or-archaeosomes
#8
A Landi, J Law, D Hockman, M Logan, K Crawford, C Chen, J Kundu, T Ebensen, C A Guzman, L Deschatelets, L Krishnan, D L J Tyrrell, M Houghton
Three decades after the discovery, hepatitis C virus (HCV) is still the leading cause of liver transplantation and poses a major threat to global health. In spite of recent advances in the development of direct acting antivirals, there is still a need for a prophylactic vaccine to limit the virus spread and protect at-risk populations, especially in developing countries, where the cost of the new treatments may severely limit access. The use of recombinant HCV glycoproteins E1E2 (rE1E2) in combination with the MF59, an oil-in-water emulsion-based adjuvant, has previously been shown to reduce the rate of chronicity in chimpanzees and to induce production of cross-neutralizing antibodies and cellular immune responses in human volunteers...
October 28, 2017: Vaccine
https://www.readbyqxmd.com/read/29074218/avasimibe-a-novel-hepatitis-c-virus-inhibitor-that-targets-the-assembly-of-infectious-viral-particles
#9
Longbo Hu, Jinqian Li, Hua Cai, Wenxia Yao, Jing Xiao, Yi-Ping Li, Xiu Qiu, Huimin Xia, Tao Peng
Direct-acting antivirals (DAAs), which target hepatitis C virus (HCV) proteins, have exhibited impressive efficacy in the management of chronic hepatitis C. However, the concerns regarding high costs, drug resistance mutations and subsequent unexpected side effects still call for the development of host-targeting agents (HTAs) that target host factors involved in the viral life cycle and exhibit pan-genotypic antiviral activity. Given the close relationship between lipid metabolism and the HCV life cycle, we investigated the anti-HCV activity of a series of lipid-lowering drugs that have been approved by government administrations or proven safety in clinical trials...
October 23, 2017: Antiviral Research
https://www.readbyqxmd.com/read/29046459/hepatitis-c-virus-replication-depends-on-endosomal-cholesterol-homeostasis
#10
Ina Karen Stoeck, Ji-Young Lee, Keisuke Tabata, Inés Romero-Brey, David Paul, Philipp Schult, Volker Lohmann, Lars Kaderali, Ralf Bartenschlager
Similar to other positive-strand RNA viruses, hepatitis C virus (HCV) causes massive rearrangements of intracellular membranes, resulting in a membranous web (MW) composed of predominantly double membrane vesicles (DMVs), the presumed sites of RNA replication. DMVs are enriched for cholesterol, but mechanistic details on the source and recruitment of cholesterol to the viral replication organelle are only partially known. Here we focused on selected lipid transfer proteins implicated in direct lipid transfer at various endoplasmic reticulum (ER) - membrane contact sites...
October 18, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28969178/association-of-serum-lipids-with-hepatic-steatosis-stage-of-liver-fibrosis-and-viral-load-in-chronic-hepatitis-c
#11
Ivan Valkov, Radina Ivanova, Assen Alexiev, Krasimir Antonov, Lyudmila Mateva
INTRODUCTION: Hepatitis C Virus (HCV) relies on host lipids for its life cycle contributing to lipid abnormalities and hepatic steatosis. Disease progression is influenced by viral factors interacting with host immune and metabolic pathways. The significance of serum lipids for Chronic Hepatitis C (CHC) assessment is not clearly established yet. AIM: Our aim was to investigate serum lipids' association with stage of liver fibrosis, steatosis and genotypes in patients with CHC...
August 2017: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/28932315/experimental-hepatic-carcinogenesis-oxidative-stress-and-natural-antioxidants
#12
REVIEW
Velid Unsal, Ergül Belge-Kurutaş
Hepatocellular carcinoma is one of the most common cancers in the world, and it is influenced by agents such as DEN, 2-AAF, phenobarbital, alcohol, aflatoxin B1 metabolite or hepatitis viruses (B and C). Oxidative stress is becoming recognized as a key factor in the progression of hepatocarcinogenesis. Reactive oxygen species can play a leading role in initiation and promotion of hepatic carcinogenesis. The metabolites of DEN Diethylnitrosamine (DEN) mediate the binding of tumour promoters by covalently binding to the DNA with one or two oxidation-providing electrons...
August 15, 2017: Open Access Macedonian Journal of Medical Sciences
https://www.readbyqxmd.com/read/28883690/direct-acting-antiviral-agents-against-hepatitis-c-virus-and-lipid-metabolism
#13
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/28877444/new-tethered-phospholipid-bilayers-integrating-functional-g-protein-coupled-receptor-membrane-proteins
#14
Meriem Chadli, Samuel Rebaud, Ofelia Maniti, Bruno Tillier, Sandra Cortès, Agnès Girard-Egrot
Membrane proteins exhibiting extra- and intracellular domains require an adequate near-native lipid platform for their functional reconstitution. With this aim, we developed a new technology enabling the formation of a peptide-tethered bilayer lipid membrane (pep-tBLM), a lipid bilayer grafted onto peptide spacers, by way of a metal-chelate interaction. To this end, we designed an original peptide spacer derived from the natural α-laminin thiopeptide (P19) possessing a cysteine residue in the N-terminal extremity for grafting onto gold and a C-terminal extremity modified by four histidine residues (P19-4H)...
September 20, 2017: Langmuir: the ACS Journal of Surfaces and Colloids
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
#15
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
#16
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/28839198/the-effect-of-the-tm6sf2-e167k-variant-on-liver-steatosis-and-fibrosis-in-patients-with-chronic-hepatitis-c-a-meta-analysis
#17
Zhengtao Liu, Shuping Que, Lin Zhou, Shusen Zheng, Stefano Romeo, Adil Mardinoglu, Luca Valenti
The impact of Transmembrane 6 superfamily member 2 (TM6SF2) E167K variant, which causes hepatocellular fat retention by altering lipoprotein secretion, on liver damage and metabolic traits in chronic hepatitis C patients is still debated. We performed a systematic review and meta-analysis to clarify this relationship. Four studies with a total of 4325 patients were included. The risk of histologically-determined advanced steatosis, fibrosis, and cirrhosis (but not of severe inflammation) were increased in carriers of the TM6SF2 variant (P < 0...
August 24, 2017: Scientific Reports
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
#18
Takako Inoue, Takaaki Goto, Etsuko Iio, Kayoko Matsunami, Kei Fujiwara, Noboru Shinkai, Kentaro Matsuura, Takeshi Matsui, Shunsuke Nojiri, Yasuhito Tanaka
AIM: 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 hepatitis C virus (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
#19
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
#20
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
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