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HCV nonstructural

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https://www.readbyqxmd.com/read/29167346/glycine-zipper-motifs-in-hepatitis-c-virus-nonstructural-protein-4b-are-required-for-the-establishment-of-viral-replication-organelles
#1
David Paul, Vanesa Madan, Omar Ramirez, Maja Bencun, Ina Karen Stoeck, Vlastimil Jirasko, Ralf Bartenschlager
Hepatitis C virus (HCV) RNA replication occurs in tight association with remodeled host cell membranes, presenting as cytoplasmic accumulations of single, double and multi membrane vesicles in infected cells. Formation of these so-called replication organelles is mediated by a complex interplay of host cell factors and viral replicase proteins. Of these, nonstructural protein 4B (NS4B), an integral transmembrane protein, appears to play a key role, but little is known about the molecular mechanisms how this protein contributes to organelle biogenesis...
November 22, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29142571/in-vitro-transcription-analysis-of-ns5a-from-hcv-3a-circulating-in-pakistani-patients-with-chronic-hepatitis-c-and-their-differential-response-to-antiviral-therapy
#2
Shameem Bhatti, Sobia Manzoor, Fahed Parvaiz, Javed Ashraf, Farakh Javed
Objective: Mutations in HCV nonstructural protein 5A (NS5A) play a vital role in virus resistance. The aim of this study was to develop a correlation between NS5A mutations (genotype 3a) and virological response towards interferon alpha (IFN-α) plus ribavirin therapy. Methods: In this study, which was conducted from 09-02-2013 to 25-11-2015 in the rural area of Province Sindh - Pakistan, total patients' responses to peg-IFN therapy were investigated. Patients were given peg-IFN therapy for 24 to 48 weeks and categorized as sustained virologic responders (SVR) or non-responders (NR) to HCV infection...
September 2017: Pakistan Journal of Medical Sciences Quarterly
https://www.readbyqxmd.com/read/29080280/usefulness-of-semiquantitative-pcr-invader-assay-for-selecting-candidates-for-daclatasvir-plus-asunaprevir-combination-therapy-among-patients-with-hepatitis-c-virus-genotype-1b
#3
Koichi Honda, Masataka Seike, Junya Oribe, Mizuki Endo, Mie Arakawa, Masanori Tokoro, Masao Iwao, Tetsu Mori, Junko Nishimura, Yukou Takahashi, Kaoru Omori, Tsutomu Yamashita, Toyokichi Muro, Kazunari Murakami
BACKGROUND & AIMS: PCR-Invader is a highly sensitive assay for detecting nonstructural protein 5A (NS5A) resistance-associated variants (RAVs) of hepatitis C virus (HCV). Here, we validated the accuracy of the semiquantitative PCR-Invader (SQ-PI) assay compared to direct sequencing (DS) for identifying NS5A RAVs, and we evaluated the treatment efficacy of daclatasvir plus asunaprevir (DCV+ASV) for patients judged to be nonpositive for NS5A RAVs by SQ-PI. METHODS: Detection rates of NS5A RAVs by SQ-PI and DS were compared for 204 patients with HCV genotype 1b...
October 28, 2017: Hepatology Research: the Official Journal of the Japan Society of Hepatology
https://www.readbyqxmd.com/read/29070684/ns3-from-hcv-strain-jfh-1-is-an-unusually-robust-helicase-that-is-primed-to-bind-and-unwind-viral-rna
#4
Ting Zhou, Xiaoming Ren, Rebecca L Adams, Anna Marie Pyle
Hepatitis C viruses (HCV) encode a helicase enzyme that is essential for viral replication and assembly (NS3). This helicase has become the focus of extensive basic research on general helicase mechanism and it is also of interest as a novel drug target. Despite the importance of this protein, mechanistic work on NS3 has been conducted almost exclusively on variants from HCV genotype 1. Our understanding of NS3 from the highly active HCV strains that are used to study HCV genetics and mechanism in cell culture (such as JFH-1) is lacking...
October 25, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28973992/3d-spatially-resolved-models-of-the-intracellular-dynamics-of-the-hepatitis-c-genome-replication-cycle
#5
Markus M Knodel, Sebastian Reiter, Paul Targett-Adams, Alfio Grillo, Eva Herrmann, Gabriel Wittum
Mathematical models of virus dynamics have not previously acknowledged spatial resolution at the intracellular level despite substantial arguments that favor the consideration of intracellular spatial dependence. The replication of the hepatitis C virus (HCV) viral RNA (vRNA) occurs within special replication complexes formed from membranes derived from endoplasmatic reticulum (ER). These regions, termed membranous webs, are generated primarily through specific interactions between nonstructural virus-encoded proteins (NSPs) and host cellular factors...
September 30, 2017: Viruses
https://www.readbyqxmd.com/read/28969940/immune-response-of-th17-associated-cytokines-by-peripheral-blood-mononuclear-cells-from-patients-with-chronic-hepatitis-c-virus-infection
#6
Milena S Cabral, Taciana P S Santos, Priscila L Santos, Maria Isabel Schinoni, Isabela S Oliveira, Ariana B Pereira, Ajax M Atta, Maria Luiza B Sousa-Atta
Hepatitis C virus (HCV) chronic infection causes severe cellular immune dysfunction. Here, we investigated the production of Th17-associated cytokines by peripheral blood mononuclear cells (PBMCs) of untreated patients with HCV, patients presenting an early virologic response (EVR) after 12weeks of treatment with interferon-α plus ribavirin with or without HCV protease inhibitors, and patients who were nonresponders to HCV therapy. PBMCs were stimulated with HCV core and nonstructural antigens, and the production of Th17-associated cytokines was measured with a Milliplex MAP immunoassay...
September 29, 2017: Cytokine
https://www.readbyqxmd.com/read/28882564/searching-for-synergy-identifying-optimal-antiviral-combination-therapy-using-hepatitis-c-virus-hcv-agents-in-a-replicon-system
#7
Justin J Pomeroy, George L Drusano, Jaime L Rodriquez, Ashley N Brown
Direct acting antiviral agents (DAAs) are potent inhibitors of Hepatitis C virus (HCV) that have revolutionized the treatment landscape for this important viral disease. There are currently four classes of DAAs that inhibit HCV replication via distinct mechanisms of action: nonstructural protein (NS) 3/4a protease inhibitors, NS5A inhibitors, NS5B nucleoside polymerase inhibitors, and NS5B non-nucleoside polymerase inhibitors. Combination therapy with two or more DAAs has great potential to further enhance antiviral potency...
October 2017: Antiviral Research
https://www.readbyqxmd.com/read/28852124/oxidative-stress-and-immune-responses-during-hepatitis-c-virus-infection-in-tupaia-belangeri
#8
Mohammad Enamul Hoque Kayesh, Sayeh Ezzikouri, Takahiro Sanada, Haiying Chi, Yukiko Hayashi, Khadija Rebbani, Bouchra Kitab, Aya Matsuu, Noriaki Miyoshi, Tsunekazu Hishima, Michinori Kohara, Kyoko Tsukiyama-Kohara
Hepatitis C virus (HCV) is a leading cause of chronic liver disease, cirrhosis, and hepatocellular carcinoma. To address the molecular basis of HCV pathogenesis using tupaias (Tupaia belangeri), we characterized host responses upon HCV infection. Adult tupaias were infected with HCV genotypes 1a, 1b, 2a, or 4a. Viral RNA, alanine aminotransferase, anti-HCV core and anti-nonstructural protein NS3 antibody titres, reactive oxygen species (ROS), and anti-3β-hydroxysterol-Δ24reductase (DHCR24) antibody levels were measured at 2-week intervals from 0 to 41 weeks postinfection...
August 29, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28833932/nonstructural-protein-5a-ns5a-resistance-profile-in-patients-with-chronic-hepatitis-c-treated-with-ledipasvir-containing-regimens-without-sofosbuvir
#9
Kathryn M Kitrinos, Amoreena C Corsa, Angela Worth, Charlotte Hedskog, Diana Brainard, Michael D Miller, Hongmei Mo
The study aimed to evaluate the effects of baseline hepatitis C virus (HCV) NS5A resistance-associated substitutions (RASs) on sustained virologic response to ledipasvir (LDV)-containing regimens in the absence of sofosbuvir (SOF) in patients with HCV genotype (GT) 1 infection across 6 phase 2 clinical studies. We analyzed data from 1103 patients who received either LDV+vedroprevir (NS3 PI)+tegobuvir (NS5B inhibitor)±ribavirin or LDV+ribavirin+pegylated interferon. Population sequencing of HCV NS5A was performed at baseline and at virologic failure from patient plasma samples...
August 20, 2017: Journal of Viral Hepatitis
https://www.readbyqxmd.com/read/28820725/understanding-hepatitis-c-virus-drug-resistance-clinical-implications-for-current-and-future-regimens
#10
David L Wyles, Anne F Luetkemeyer
Viral resistance to direct-acting antiviral drugs may impact their effectiveness during treatment of hepatitis C virus (HCV) infection. Most data on HCV drug resistance concern genotypes 1 and 3. The clinical impact of resistance to HCV nonstructural protein 5A (NS5A) inhibitors and a practical approach to indications and methods for resistance testing are discussed.
July 2017: Topics in Antiviral Medicine
https://www.readbyqxmd.com/read/28815532/hepatitis-c-virus-replication
#11
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/28809743/outcomes-for-cirrhotic-patients-with-hepatitis-c-virus-1b-treated-with-asunaprevir-and-daclatasvir-combination
#12
Akihiro Tamori, Hoang Hai, Sawako Uchida-Kobayashi, Masaru Enomoto, Ritsuzo Kozuka, Hiroyuki Motoyama, Etsushi Kawamura, Atsushi Hagihara, Yuga Teranishi, Kanako Yoshida, Hiroyasu Morikawa, Yoshiki Murakami, Norifumi Kawada
BACKGROUND: The efficacy and safety of asunaprevir + daclatasvir combination therapy for treatment of hepatitis C virus (HCV) in compensated cirrhotic patients was not fully evaluated in real-world. Outcomes were assessed in cirrhotic patients with sustained viral response (SVR). MATERIAL AND METHODS: A total of 145 patients without resistance-associated substitutions (RASs) at L31 and Y93 in the nonstructural protein 5A of HCV genotype 1b, consisting of 49 hepatic cirrhotic and 96 non-cirrhotic patients, were enrolled to the therapy...
September 2017: Annals of Hepatology
https://www.readbyqxmd.com/read/28807904/no-clinically-relevant-drug-drug-interactions-between-methadone-or-buprenorphine-naloxone-and-antiviral-combination-glecaprevir-and-pibrentasvir
#13
Matthew P Kosloski, Weihan Zhao, Armen Asatryan, Jens Kort, Pierre Geoffroy, Wei Liu
The combination of glecaprevir (formerly ABT-493), a nonstructural protein 3/4A (NS3/4A) protease inhibitor, and pibrentasvir (formerly ABT-530), an NS5A protein inhibitor, is being developed as treatment for HCV genotype 1 to 6 infection. The pharmacokinetics, pharmacodynamics, safety, and tolerability of methadone or buprenorphine-naloxone when coadministered with the glecaprevir-pibrentasvir combination in HCV-negative subjects on stable opioid maintenance therapy were investigated in a phase 1, single-center, two-arm, multiple-dose, open-label sequential study...
October 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28758632/tree-shrew-a-potential-animal-model-for-hepatitis-c-supports-the-infection-and-replication-of-hcv-in-vitro-and-in-vivo
#14
Yue Feng, Yue-Mei Feng, Caixia Lu, Yuanyuan Han, Li Liu, Xiaomei Sun, Jiejie Dai, Xueshan Xia
The tree shrew (Tupaia belangeri chinensis), a small animal widely distributed in Southeast Asia and southwest China, has the potential to be developed as an animal model for hepatitis C. To determine the susceptibility of the tree shrew to hepatitis C virus (HCV) infection in vitro and in vivo, a well-established HCV, produced from the J6/JFH1-Huh7.5.1 culture system, was used to infect cultured primary tupaia hepatocytes (PTHs) and tree shrews. The in vitro results showed that HCV genomic RNA and HCV-specific nonstructural protein 5A (NS5A) could be detected in the PTH cell culture from days 3-15 post-infection, although the viral load was lower than that observed in Huh7...
August 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28747506/hepatitis-c-virus-induces-the-localization-of-lipid-rafts-to-autophagosomes-for-its-rna-replication
#15
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 an HCV subgenomic RNA replicon. The purified autophagosomes had double- or multiple-membrane structures with a diameter ranging from 200 nm to 600 nm...
October 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28746382/gelatin-nanoparticles-enhance-delivery-of-hepatitis-c-virus-recombinant-ns2-gene
#16
Salwa Sabet, Marina A George, Haidan M El-Shorbagy, Heba Bassiony, Khaled Y Farroh, Tareq Youssef, Taher A Salaheldin
BACKGROUND: Development of an effective non-viral vaccine against hepatitis C virus infection is of a great importance. Gelatin nanoparticles (Gel.NPs) have an attention and promising approach as a viable carrier for delivery of vaccine, gene, drug and other biomolecules in the body. AIM OF WORK: The present study aimed to develop stable Gel.NPs conjugated with nonstructural protein 2 (NS2) gene of Hepatitis C Virus genotype 4a (HCV4a) as a safe and an efficient vaccine delivery system...
2017: PloS One
https://www.readbyqxmd.com/read/28687550/sofosbuvir-velpatasvir-a-single-tablet-treatment-for-hepatitis-c-infection-of-all-genotypes
#17
REVIEW
Misty M Miller
PURPOSE: The pharmacology, pharmacokinetics, interaction potential, efficacy, and safety of the newest direct-acting antiviral (DAA) medication for the treatment of chronic hepatitis C are reviewed. SUMMARY: Nonstructural proteins 5A (NS5A) and 5B (NS5B) are key drivers of hepatitis C virus (HCV) replication. Velpatasvir, an inhibitor of NS5A, was coformulated with the NS5B inhibitor sofosbuvir to provide a single-tablet combination DAA (Epclusa, Gilead Sciences)...
July 15, 2017: American Journal of Health-system Pharmacy: AJHP
https://www.readbyqxmd.com/read/28643404/occurrence-of-late-relapse-of-hepatitis-c-virus-confirmed-by-molecular-analysis-after-sustained-virologic-response-to-interferon-ribavirin-based-therapy
#18
Kazuhiko Hayashi, Masatoshi Ishigami, Satoshi Yasuda, Yoji Ishizu, Teiji Kuzuya, Takashi Honda, Tetsuya Ishikawa, Yoshiki Hirooka, Hidemi Goto
AIM: The optimal duration of follow-up for patients who achieve sustained virologic responses (SVR) has become an important issue. Reports on long-term follow-up of SVR have indicated that 99% of patients maintained SVR. However, the limitations of a majority of studies include small patient numbers, short study periods, and lack of molecular analysis of hepatitis C virus (HCV) genome. The present study sought to evaluate the late relapse rate in long-term follow-up of patients who achieved SVR, with molecular analysis of HCV...
June 22, 2017: Hepatology Research: the Official Journal of the Japan Society of Hepatology
https://www.readbyqxmd.com/read/28621007/effectiveness-of-a-fixed-combination-formula-of-ombitasvir-paritaprevir-ritonavir-for-hepatitis-c-virus-infection-in-patients-on-maintenance-haemodialysis
#19
Norihiko Morisawa, Yohei Koshima, Satoru Kuriyama, Momoko Matsuyama, Naomi Hayashi, Jun-Ichi Satoh, Morimasa Amemiya, Takashi Yokoo
A fixed-dose formula that combines Ombitasvir (OBV), Paritaprevir (PTV) and Ritonavir (RTV) has been launched into the field of anti-HCV therapy in Japan for patients infected with HCV genotypes 1 and 2 in 2015. However, little is yet known as to the efficacy and safety of this novel therapy in patients on maintenance haemodialysis (HD). The present report describes a preliminary experience in 10 patients (five males and five females) who underwent maintenance HD. All of them had HCV genotype 1b, without having the resistance-associated variants at Y93 or L31 in the nonstructural proteins 5A (NS5A) region...
July 2017: Nephrology
https://www.readbyqxmd.com/read/28619163/frequent-occurrence-of-nonprimate-hepacivirus-infections-in-thoroughbred-breeding-horses-a-cross-sectional-study-for-the-occurrence-of-infections-and-potential-risk-factors
#20
Claudia Reichert, Amely Campe, Stephanie Walter, Stephanie Pfaender, Kathrin Welsch, Inga Ruddat, Harald Sieme, Karsten Feige, Eike Steinmann, Jessika M V Cavalleri
Recently, several new hepaciviruses have been identified of which the nonprimate hepacivirus (NPHV) - the closest relative to hepatitis C virus (HCV) discovered to date - is highly prevalent in horses. However, potential risk factors for the transmission of NPHV among horses remain still unknown. Therefore, the objective of this study was to investigate the occurrence of NPHV infections in Thoroughbreds in northern and western Germany and to identify potential risk factors associated with NPHV infections. Using a cross-sectional study design, a total of 733 serum samples from Thoroughbred broodmares and stallions from northern and western Germany were analyzed for the presence of anti-NPHV nonstructural protein 3 (NS3) antibodies and NPHV RNA using the luciferase immunoprecipitation system (LIPS) and a quantitative real-time PCR, respectively...
May 2017: Veterinary Microbiology
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