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Hepatitis C virus lipids

Sascha Suffner, Nadine Gerstenberg, Maria Patra, Paula Ruibal, Ahmed Orabi, Michael Schindler, Volker Bruss
During hepatitis B virus infections subviral particles (SVP) consisting only of viral envelope proteins and lipids are secreted. Heterologous expression of the small envelope protein S in mammalian cells is sufficient for SVP generation. S is synthesized as a transmembrane protein with N-terminal (TM1), central (TM2), and C-terminal (HCR) transmembrane domains. The loops between TM1 and TM2 (CL) and between TM2 and HCR (LL) are located in the cytosol and in the ER lumen, respectively. To define domains of S mediating oligomerization during SVP morphogenesis S mutants were characterized by expression in transiently transfected cells...
March 14, 2018: Journal of Virology
Vladimir Alexei Morozov, Sylvie Lagaye
Hepatitis C virus (HCV) is a major cause of liver diseases including liver cirrhosis and hepatocellular carcinoma. Approximately 3% of the world population is infected with HCV. Thus, HCV infection is considered a public healthy challenge. It is worth mentioning, that the HCV prevalence is dependent on the countries with infection rates around 20% in high endemic countries. The review summarizes recent data on HCV molecular biology, the physiopathology of infection (immune-mediated liver damage, liver fibrosis and lipid metabolism), virus diagnostic and treatment...
February 27, 2018: World Journal of Hepatology
Sadia Qamar Arain, Farah Naz Talpur, Naseem Aslam Channa, Muhammad Shahbaz Ali, Hassan Imran Afridi
BACKGROUND: Hepatitis B virus (HBV) exerts an intense impact on host lipid metabolism. Hence the aim of present study is to determine metabolic derangement that occurred in subjects suffering from hepatitis B patients. METHODS: The fasting blood samples were collected from hepatitis B patients (n = 50) attended in Taluka hospital TandoAdam, Sindh with age and gender matched controls (n = 50). Serum lipid profile and fatty acid (FA) composition were analyzed by micro-lab and gas chromatography...
March 5, 2018: Lipids in Health and Disease
Ghada El Sagheer, Elwy Soliman, Asmaa Ahmad, Lamiaa Hamdy
Chronic hepatitis C virus (HCV) infection is associated with altered metabolism, including dyslipidemia and insulin resistance. These contribute to disease progression and influences the response to therapy. To investigate the relationships of new direct-acting antiviral drugs, simeprevir/sofosbuvir, with lipid profile and insulin resistance (IR). Eighty chronic hepatitis C genotype 4 patients were included; they were divided into four groups according to the severity of fibrosis as detected by fibroscan. Forty healthy persons volunteered as a control group...
December 2018: Libyan Journal of Medicine
Simon H Bridge, Sabrina Pagano, Meleri Jones, Graham R Foster, Dermot Neely, Nicolas Vuilleumier, Margaret F Bassendine
BACKGROUND/PURPOSE: One to three per cent of the world's population has hepatitis C virus (HCV) infection, which is not only a major cause of liver disease and cancer but also associated with an increased risk of atherosclerosis, despite an ostensibly favourable lipid profile. Autoantibodies are frequent in HCV infection and emerging evidence shows that autoantibodies could be valuable for cardiovascular disease (CVD) risk stratification. This study investigated a novel independent biomarker of CVD, autoantibodies to apolipoprotein A-1 (anti-apoA-1 IgG) and lipids in patients with chronic HCV before, during and after direct-acting anti-viral (DAA) therapy...
February 8, 2018: Hepatology International
Shinya Satoh, Kyoko Mori, Daichi Onomura, Youki Ueda, Hiromichi Dansako, Masao Honda, Shuichi Kaneko, Masanori Ikeda, Nobuyuki Kato
Ribavirin (RBV) has been widely used as an antiviral reagent, specifically for patients with chronic hepatitis C. We previously demonstrated that adenosine kinase, which monophosphorylates RBV into the metabolically active form, is a key determinant for RBV sensitivity against hepatitis C virus RNA replication. However, the precise mechanism of RBV action and whether RBV affects cellular metabolism remain unclear. Analysis of liver gene expression profiles obtained from patients with advanced chronic hepatitis C treated with the combination of pegylated interferon and RBV showed that the adenosine kinase expression level tends to be lower in patients who are overweight and significantly decreases with progression to advanced fibrosis stages...
August 2017: Hepatology Communications
Yu-Min Lin, Hung-Yu Sun, Wen-Tai Chiu, Hui-Chen Su, Yu-Chieh Chien, Lee-Won Chong, Hung-Chuen Chang, Chyi-Huey Bai, Kung-Chia Young, Chiung-Wen Tsao
Vitamin D has been identified as an innate anti-hepatitis C virus (HCV) agent but the possible mechanisms for this issue remain unclear. Here, we clarified the mechanisms of calcitriol-mediated inhibition of HCV infection. Calcitriol partially inhibited HCV infection, nitric oxide (NO) release and lipid accumulation in Huh7.5 human hepatoma cells via the activation of vitamin D receptor (VDR). When cells were pretreated with the activators of peroxisome proliferator-activated receptor (PPAR)-α (Wy14643) and -γ (Ly171883), the calcitriol-mediated HCV suppression was reversed...
January 30, 2018: Viruses
Rie Harada, Masako Kimura, Yasushi Sato, Tatsuya Taniguchi, Tetsu Tomonari, Takahiro Tanaka, Hironori Tanaka, Naoki Muguruma, Hirohiko Shinomiya, Hirohito Honda, Issei Imoto, Masahiro Sogabe, Toshiya Okahisa, Tetsuji Takayama
BACKGROUND: It has been reported that some single-nucleotide polymorphisms (SNPs) in lipid regulators such as apolipoproteins and cell surface molecules for hepatitis C virus (HCV) entry into hepatocytes are associated with HCV infection. However, it is unknown how HCV infection is affected by altered lipid metabolism resulting from the SNPs. We investigated the relationship between these SNPs and HCV infection status, and also analyzed the mechanism by which these SNPs mediate HCV infection via lipid metabolism alterations...
January 30, 2018: BMC Gastroenterology
Chunhong Yin, Niluka Goonawardane, Hazel Stewart, Mark Harris
The NS5A protein of hepatitis C virus (HCV) plays roles in both virus genome replication and assembly. NS5A comprises three domains, of these domain I is believed to be involved exclusively in genome replication. In contrast, domains II and III are required for the production of infectious virus particles and are largely dispensable for genome replication. Domain I is highly conserved between HCV and related hepaciviruses, and is highly structured, exhibiting different dimeric conformations. To investigate the functions of domain I in more detail, we conducted a mutagenic study of 12 absolutely conserved and surface-exposed residues within the context of a JFH-1-derived sub-genomic replicon and infectious virus...
January 19, 2018: PLoS Pathogens
Mervat Morsy Abbas Ahmed El-Gendy, Shaymaa M M Yahya, Ahmed R Hamed, Maha M Soltan, Ahmed Mohamed Ahmed El-Bondkly
Forty-four endophytic fungal isolates obtained from marine sponge, Hyrtios erectus, were evaluated and screened for their hydrolase activities. Most of the isolates were found to be prolific producers of hydrolytic enzymes. Only 11 isolates exhibited maximum cellular contents of lipids, rhamnolipids, and protein in the fungal isolates under the isolation numbers MERVA5, MERVA22, MERVA25, MERVA29, MERVA32, MERVA34, MERV36, MERVA39, MERVA42, MERVA43, and MERVA44. These isolate extracts exhibit the highest reducing activities against carbohydrate-metabolizing enzymes including α-amylase, α-glucosidase, β-glucosidase, β-glucuronidase, and tyrosinase...
January 12, 2018: Applied Biochemistry and Biotechnology
Stefano Gitto, Arrigo F G Cicero, Elisabetta Loggi, Marina Giovannini, Fabio Conti, Elena Grandini, Valeria Guarneri, Alessandra Scuteri, Giovanni Vitale, Carmela Cursaro, Claudio Borghi, Pietro Andreone
INTRODUCTION: Host lipid metabolism influences viral replication and lifecycle of hepatitis C virus. Our aim was to evaluate changes in glucose and lipid metabolism of patients with chronic hepatitis C after therapy with direct acting antivirals (DAA). MATERIAL AND METHODS: We considered patients consecutively treated between January and November 2015 recording clinical data at baseline and week 24 of follow-up. Frozen serum samples were used for apolipoprotein A1 (apoA1), apolipoprotein B (apoB) and lipoprotein (a) [Lp(a)]...
January 2018: Annals of Hepatology
Usman Ali Ashfaq, Hina Khalid
The hepatitis C virus (HCV), the most predominant cause of liver failure worldwide, is associated with the development of diabetes mellitus (DM) and insulin resistance (IR), both in vivo and in vitro. DM and IR aggravate the rate of fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Most studies have revealed that patients with HCV are at a greater risk of developing type 2 diabetes (T2D), compared with controls or patients with hepatitis B. In the same way, patients with T2D are highly prone to severe HCV clinical outcomes and increased progression to fibrosis and cirrhosis, ultimately leading to HCC...
2017: Critical Reviews in Eukaryotic Gene Expression
Mar Rodríguez-Rodríguez, Daniel Tello, Julián Gómez-Gutiérrez, Darrell L Peterson, Francisco Gavilanes, Belén Yélamos
The steps leading from hepatitis C virus (HCV) attachment to the hepatocytes to the fusion of viral and cellular membranes remain uncharacterized. In this regard, we have studied the mechanism underlying the HCV fusion process using liposomes and a truncated form of E2 protein lacking the transmembrane region, E2661 (amino acids 384-661). E2661 has been previously obtained by using the baculovirus expression system and shown to behave as an independent folding domain (M. Rodriguez-Rodriguez, D. Tello, B. Yelamos, J...
December 19, 2017: Biochimica et Biophysica Acta
Zhubing Li, Qiang Liu
Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a serine protease actively involved in regulating lipid homeostasis. Although PCSK9 has been shown to inhibit hepatitis C virus (HCV) entry and replication, the underlying mechanisms have not been thoroughly characterized. Moreover, whether PCSK9 regulates HCV translation and assembly/secretion has not been determined. We therefore further studied the effects of PCSK9 on the HCV life cycle. We showed that PCSK9 did not affect HCV translation or assembly/secretion...
December 13, 2017: Journal of General Virology
Jingshu Zhang, Yun Lan, Sumana Sanyal
Lipid droplets (LDs) are endoplasmic reticulum (ER)-related dynamic organelles that store and regulate fatty acids and neutral lipids. They play a central role in cellular energy storage, lipid metabolism and cellular homeostasis. It has become evident that viruses have co-evolved in order to exploit host lipid metabolic pathways. This is especially characteristic of the Flaviviridae family, including hepatitis C virus (HCV) and several flaviviruses. Devoid of an appropriate lipid biosynthetic machinery of their own, these single-strand positive-sense RNA viruses can induce dramatic changes in host metabolic pathways to establish a favorable environment for viral multiplication and acquire essential components to facilitate their assembly and traffic...
2017: Frontiers in Microbiology
Takeshi Chida, Kazuhito Kawata, Kazuyoshi Ohta, Erika Matsunaga, Jun Ito, Shin Shimoyama, Satoru Yamazaki, Hidenao Noritake, Tetsuro Suzuki, Takafumi Suda, Yoshimasa Kobayashi
Background/Aims: Changes in lipid profiles in patients infected with hepatitis C virus (HCV) during direct-acting antiviral therapy have been reported in recent years. However, the clinical aspects of disturbed lipid metabolism in chronic HCV infection have not been fully elucidated. Methods: Dynamic changes in serum total, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) cholesterol and apolipoprotein levels in patients infected with HCV genotype 1b were examined during combination therapy with daclatasvir (DCV) and asunaprevir (ASV)...
March 15, 2018: Gut and Liver
Jun Zhang, Qian Wang, Xing Zhao, Laidi Wang, Xingguo Wang, Jian Wang, Biao Dong, Daoqing Gong
MicroRNA-122 (miR-122), a completely conserved, liver-specific miRNA in vertebrates, is essential for the maintenance of liver homeostasis. This 22-nucleotide-length RNA regulates diverse functions such as cholesterol, glucose, and lipid metabolism as well as iron homeostasis and infection of hepatitis C virus (HCV). Landes goose, which has a good, fatty liver, has important significance for us in studying miR-122 function in goose fatty liver. In the current study, we identified miR-122 in goose liver and its expression pattern and target genes...
February 1, 2018: Poultry Science
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
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...
December 27, 2017: Journal of Infectious Diseases
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...
December 5, 2017: Proceedings of the National Academy of Sciences of the United States of America
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