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HCV nonstructural

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https://www.readbyqxmd.com/read/28820725/understanding-hepatitis-c-virus-drug-resistance-clinical-implications-for-current-and-future-regimens
#1
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
#2
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
#3
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...
August 8, 2017: Annals of Hepatology
https://www.readbyqxmd.com/read/28807904/no-clinically-relevant-drug-drug-interactions-between-methadone-or-buprenorphine-naloxone-and-anti-viral-combination-glecaprevir-and-pibrentasvir
#4
Matthew Kosloski, Weihan Zhao, Armen Asatryan, Jens Kort, Pierre Geoffroy, Wei Liu
The combination of glecaprevir (formerly ABT-493), a nonstructural (NS) protein 3/4A protease inhibitor, and pibrentasvir (formerly ABT-530), a NS5A protein inhibitor, is being developed as treatment for HCV genotype 1-6 infection. The pharmacokinetics, pharmacodynamics, safety, and tolerability of methadone or buprenorphine/naloxone when coadministered with the glecaprevir and 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...
August 14, 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
#5
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...
July 31, 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28747506/hcv-induces-the-localization-of-lipid-rafts-to-autophagosomes-for-its-rna-replication
#6
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/28746382/gelatin-nanoparticles-enhance-delivery-of-hepatitis-c-virus-recombinant-ns2-gene
#7
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
#8
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
#9
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
#10
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
#11
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
https://www.readbyqxmd.com/read/28572406/how-an-alloreactive-t-cell-receptor-achieves-peptide-and-mhc-specificity
#12
Yuan Wang, Nishant K Singh, Timothy T Spear, Lance M Hellman, Kurt H Piepenbrink, Rachel H McMahan, Hugo R Rosen, Craig W Vander Kooi, Michael I Nishimura, Brian M Baker
T-cell receptor (TCR) allorecognition is often presumed to be relatively nonspecific, attributable to either a TCR focus on exposed major histocompatibility complex (MHC) polymorphisms or the degenerate recognition of allopeptides. However, paradoxically, alloreactivity can proceed with high peptide and MHC specificity. Although the underlying mechanisms remain unclear, the existence of highly specific alloreactive TCRs has led to their use as immunotherapeutics that can circumvent central tolerance and limit graft-versus-host disease...
June 13, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28570623/genetic-diversity-of-hepatitis-c-virus-in-ethiopia
#13
Gadissa Bedada Hundie, V Stalin Raj, Daniel GebreMichael, Suzan D Pas, Bart L Haagmans
Hepatitis C virus (HCV) is genetically highly divergent and classified in seven major genotypes and approximately hundred subtypes. These genotypes/subtypes have different geographic distribution and response to antiviral therapy. In Ethiopia, however, little is known about their molecular epidemiology and genetic diversity. The aim of this study was to investigate the distribution and genetic diversity of HCV genotypes/subtypes in Ethiopia, using 49 HCV RNA positive samples. HCV genotypes and subtypes were determined based on the sequences of the core and the nonstructural protein 5B (NS5B) genomic regions...
2017: PloS One
https://www.readbyqxmd.com/read/28566381/hepatitis-c-virus-subverts-human-choline-kinase-%C3%AE-to-bridge-phosphatidylinositol-4-kinase-iii%C3%AE-pi4kiii%C3%AE-and-ns5a-and-upregulates-pi4kiii%C3%AE-activation-thereby-promoting-the-translocation-of-the-ternary-complex-to-the-endoplasmic-reticulum-for-viral-replication
#14
Mun-Teng Wong, Steve S Chen
In this study, we elucidated the mechanism by which human choline kinase-α (hCKα) interacts with nonstructural protein 5A (NS5A) and phosphatidylinositol-4-kinase IIIα (PI4KIIIα), the lipid kinase crucial for maintaining the integrity of virus-induced membranous webs, and modulates hepatitis C virus (HCV) replication. hCKα activity positively modulated phosphatidylinositol-4-phosphate (PI4P) levels in HCV-expressing cells, and hCKα-mediated PI4P accumulation was abolished by AL-9, a PI4KIIIα-specific inhibitor...
August 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28560477/daclatasvir-and-asunaprevir-in-hemodialysis-patients-with-hepatitis-c-virus-infection-a-nationwide-retrospective-study-in-japan
#15
Goki Suda, Norihiro Furusyo, Hidenori Toyoda, Yoshiiku Kawakami, Hiroki Ikeda, Michihiro Suzuki, Keiko Arataki, Nami Mori, Keiji Tsuji, Yoshio Katamura, Koichi Takaguchi, Toru Ishikawa, Kunihiko Tsuji, Noritomo Shimada, Atsushi Hiraoka, Sho Yamsaki, Masato Nakai, Takuya Sho, Kenichi Morikawa, Koji Ogawa, Mineo Kudo, Atsushi Nagasaka, Ken Furuya, Yoshiya Yamamoto, Kanji Kato, Yoshiyuki Ueno, Etsuko Iio, Yasuhito Tanaka, Masayuki Kurosaki, Takashi Kumada, Kazuaki Chayama, Naoya Sakamoto
BACKGROUND: Hepatitis C virus (HCV) infection is common in hemodialysis patients and worsens their prognosis, while antiviral therapy options are limited. Recently, clinical trial and real-world, small-scale studies have reported excellent responses to direct-acting antivirals in patients with advanced chronic kidney diseases. However, real-world, large-scale data were lacking. This large multicenter analysis included HCV-infected hemodialysis patients receiving combination therapy with a nonstructural protein 5A (NS5A) inhibitor, daclatasvir (DCV), and a protease inhibitor, asunaprevir (ASV)...
May 30, 2017: Journal of Gastroenterology
https://www.readbyqxmd.com/read/28545480/effects-of-hepatitis-c-virus-core-protein-and-nonstructural-protein-4b-on-the-wnt-%C3%AE-catenin-pathway
#16
Xiao-Hua Jiang, Yu-Tao Xie, Ya-Ping Cai, Jing Ren, Tao Ma
BACKGROUND: Hepatitis C virus (HCV) core protein and nonstructural protein 4B (NS4B) are potentially oncogenic. Aberrant activation of the Wnt/β-catenin signaling pathway is closely associated with hepatocarcinogenesis. We investigated the effects of HCV type 1b core protein and NS4B on Wnt/β-catenin signaling in various liver cells, and explored the molecular mechanism underlying HCV-related hepatocarcinogenesis. RESULTS: Compared with the empty vector control, HCV core protein and NS4B demonstrated the following characteristics in the Huh7 cells: significantly enhanced β-catenin/Tcf-dependent transcriptional activity (F = 40...
May 25, 2017: BMC Microbiology
https://www.readbyqxmd.com/read/28535337/overall-structural-model-of-ns5a-protein-from-hepatitis-c-virus-and-modulation-by-mutations-confering-resistance-of-virus-replication-to-cyclosporin-a
#17
Aurelie Badillo, Véronique Receveur-Brechot, Stéphane Sarrazin, François-Xavier Cantrelle, Frédéric Delolme, Marie-Laure Fogeron, Jennifer Molle, Roland Montserret, Anja Bockmann, Ralf Bartenschlager, Volker Lohmann, Guy Lippens, Sylvie Ricard-Blum, Xavier Hanoulle, François Penin
Hepatitis C virus (HCV) nonstructural protein 5A (NS5A) is a RNA-binding phosphoprotein composed of a N-terminal membrane anchor (AH), a structured domain 1 (D1), and two intrinsically disordered domains (D2 and D3). The knowledge of the functional architecture of this multifunctional protein remains limited. We report here that NS5A-D1D2D3 produced in a wheat germ cell-free system is obtained under a highly phosphorylated state. Its NMR analysis revealed that these phosphorylations do not change the disordered nature of D2 and D3 domains but increase the number of conformers due to partial phosphorylations...
June 7, 2017: Biochemistry
https://www.readbyqxmd.com/read/28471365/structural-features-of-ns3-of-dengue-virus-serotypes-2-and-4-in-solution-and-insight-into-rna-binding-and-the-inhibitory-role-of-quercetin
#18
Ankita Pan, Wuan Geok Saw, Malathy Sony Subramanian Manimekalai, Ardina Grüber, Shin Joon, Tsutomu Matsui, Thomas M Weiss, Gerhard Grüber
Dengue virus (DENV), which has four serotypes (DENV-1 to DENV-4), is the causative agent of the viral infection dengue. DENV nonstructural protein 3 (NS3) comprises a serine protease domain and an RNA helicase domain which has nucleotide triphosphatase activities that are essential for RNA replication and viral assembly. Here, solution X-ray scattering was used to provide insight into the overall structure and flexibility of the entire NS3 and its recombinant helicase and protease domains for Dengue virus serotypes 2 and 4 in solution...
May 1, 2017: Acta Crystallographica. Section D, Structural Biology
https://www.readbyqxmd.com/read/28446674/broadening-cd4-and-cd8-t-cell-responses-against-hepatitis-c-virus-by-vaccination-with-ns3-overlapping-peptide-panels-in-cross-priming-liposomes
#19
Jonathan Filskov, Marianne Mikkelsen, Paul R Hansen, Jan P Christensen, Allan R Thomsen, Peter Andersen, Jens Bukh, Else Marie Agger
Despite the introduction of effective drugs to treat patients with chronic hepatitis C virus (HCV) infection, a vaccine would be the only means to substantially reduce the worldwide disease burden. An incomplete understanding of how HCV interacts with its human host and evades immune surveillance has hampered vaccine development. It is generally accepted that in infected individuals, a narrow repertoire of exhausted T cells is a hallmark of persistent infection, whereas broad, vigorous CD4(+) and CD8(+) T cell responses are associated with control of acute hepatitis C...
July 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28410425/the-cobas%C3%A2-hcv-gt-is-a-new-tool-that-accurately-identifies-hepatitis-c-virus-genotypes-for-clinical-practice
#20
COMPARATIVE STUDY
J A Fernández-Caballero, M Alvarez, N Chueca, A B Pérez, F García
OBJECTIVE: We aimed to evaluate the correct assignment of HCV genotype/subtypes 1a and 1b by cobas® HCV genotyping (GT) assay (Roche Molecular Diagnostics) compared with nonstructural protein 5B (NS5B) sequencing. PATIENTS AND METHODS: Clinical samples from 153 patients submitted for HCV genotyping were studied. After genotyping with the cobas® HCV GT, sequencing of a 387 bp fragment in the NS5B gene and phylogenetic analysis was employed to compare genotyping results...
2017: PloS One
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