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Hepatitis C virus lipids

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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/28877444/new-tethered-phospholipid-bilayers-integrating-functional-g-protein-coupled-receptor-membrane-protein
#2
Meriem Chadli, Samuel Rebaud, Ofelia Maniti, Bruno Tillier, Sandra Cortès, Agnes Girard-Egrot
Membrane proteins exhibiting extra- and intra-cellular 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 the 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 N-terminal extremity for grafting on gold and modified in C-terminal extremity by four histidine residues (P19-4H)...
September 6, 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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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/28809547/quantitative-evaluation-of-viral-protein-binding-to-phosphoinositide-receptors-and-pharmacological-inhibition
#9
Seong-Oh Kim, Joshua A Jackman, Menashe Elazar, Sang-Joon Cho, Jeffrey S Glenn, Nam-Joon Cho
There is significant interest in developing analytical methods to characterize molecular recognition events between proteins and phosphoinositides, which are a medically important class of carbohydrate-functionalized lipids. Within this scope, one area of high priority involves quantitatively evaluating drug candidates that pharmacologically inhibit protein-phosphoinositide interactions. As full-length proteins are often difficult to produce, establishing methods to study these interactions with shorter, bioactive peptides would be advantageous...
August 28, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28791972/hcv-co-infection-is-associated-with-metabolic-abnormalities-among-haart-naive-hiv-infected-persons
#10
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/28761978/propolis-alleviates-concanavalin-a-induced-hepatitis-by-modulating-cytokine-secretion-and-inhibition-of-reactive-oxygen-species
#11
Fatma Mounieb, Laila Ramadan, El-Sayed Akool, Amany Balah
Viral hepatitis-induced oxidative stress accompanied by increased levels of transforming growth factor-β (TGF-β) and hepatic fibrosis are hallmarks of hepatitis C virus infection. The present study was designed to investigate the potential protective effect of propolis against liver injury induced by concanavalin A (Con A), a T-cell-dependent model that causes an immune-mediated hepatitis in a similar pattern to the one induced by viral infections. In the present study, rats were randomly divided into four groups...
July 31, 2017: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/28755365/wheat-germ-cell-free-overexpression-for-the-production-of-membrane-proteins
#12
Marie-Laure Fogeron, Aurélie Badillo, François Penin, Anja Böckmann
Due to their hydrophobic nature, membrane proteins are notoriously difficult to express in classical cell-based protein expression systems. Often toxic, they also undergo degradation in cells or aggregate in inclusion bodies, making delicate issues further solubilization and renaturation. These are major bottlenecks in their structural and functional analysis. The wheat germ cell-free (WGE-CF) system offers an effective alternative not only to classical cell-based protein expression systems but also to other cell-free systems for the expression of membrane proteins...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28747506/hcv-induces-the-localization-of-lipid-rafts-to-autophagosomes-for-its-rna-replication
#13
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/28745269/hepatitis-b-virus-prevents-excessive-viral-production-via-reduction-of-cell-death-inducing-dff45-like-effectors
#14
Jun Yasumoto, Hirotake Kasai, Kentaro Yoshimura, Teruhime Otoguro, Koichi Watashi, Takaji Wakita, Atsuya Yamashita, Tomohisa Tanaka, Sen Takeda, Kohji Moriishi
The relationship between hepatitis B virus (HBV) infection and lipid accumulation remains largely unknown. In this study, we investigated the effect of HBV propagation on lipid droplet growth in HBV-infected cells and HBV-producing cell lines, HepG2.2.15 and HBV-inducible Hep38.7-Tet. The amount of intracellular triglycerides was significantly reduced in HBV-infected and HBV-producing cells compared with HBV-lacking control cells. Electron and immunofluorescent microscopic analyses showed that the average size of a single lipid droplet (LD) was significantly less in the HBV-infected and HBV-producing cells than in the HBV-lacking control cells...
July 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28729862/rad51-interacts-with-non-structural-3-protein-of-hepatitis-c-virus-and-regulates-viral-production
#15
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
#16
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
#17
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
#18
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/28707319/tenofovir-disoproxil-fumarate-significantly-decreases-serum-lipoprotein-levels-compared-with-entecavir-nucleos-t-ide-analogue-therapy-in-chronic-hepatitis-b-carriers
#19
A A Shaheen, M AlMattooq, S Yazdanfar, K W Burak, M G Swain, S E Congly, M A Borman, S S Lee, R P Myers, C S Coffin
BACKGROUND: Tenofovir disoproxil fumarate (TDF) and entecavir (ETV) are first-line treatments for chronic hepatitis B (CHB). Studies suggest lipid lowering effect of TDF in human immunodeficiency virus positive (HIV+) individuals, but the effect on lipids and cardiovascular disease (CVD) risk in CHB is unknown. AIM: To compare TDF vs ETV effects on lipid levels in CHB. METHODS: In this retrospective cohort study, data on serum lipids and CVD risk factors at baseline and ~1 year on TDF or ETV were collected from CHB carriers...
September 2017: Alimentary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28689587/metabolic-manifestations-of-hepatitis-c-virus-diabetes-mellitus-dyslipidemia
#20
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
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