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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
#1
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
https://www.readbyqxmd.com/read/28410411/hepatitis-c-virus-impairs-natural-killer-cell-activity-via-viral-serine-protease-ns3
#2
Chang Mo Yang, Joo Chun Yoon, Jeon Han Park, Jae Myun Lee
Hepatitis C virus (HCV) infection is characterized by a high frequency of chronic cases owing to the impairment of innate and adaptive immune responses. The modulation of natural killer (NK) cell functions by HCV leads to an impaired innate immune response. However, the underling mechanisms and roles of HCV proteins in this immune evasion are controversial, especially in the early phase of HCV infection. To investigate the role of HCV nonstructural proteins especially NS3 in the impairment of NK functions, NK cells were isolated from the PBMCs by negative selection...
2017: PloS One
https://www.readbyqxmd.com/read/28367737/circulating-levels-of-collagen-iii-and-mmp-1-in-patients-with-chronic-hepatitis-c-co-infected-with-hepatitis-b-virus
#3
Abdelfattah M Attallah, Mohamed El-Far, Mohamed F Ghaly, Mohamed M Omran, Mohamed S Albannan, Ahmed A Attallah, Tarek M Shoghey, Mohamed M Atrees, Mohamed S Elbendary, Khaled Farid
BACKGROUND: There is controversial data in the literature about the characteristics and features of dual hepatitis B and hepatitis C infection. This work is concerned with estimating the extent to which HBV could influence circulating levels of hepatitis C viral nonstructural-4 (HCV-NS4) in addition to some direct fibrosis markers in chronic hepatitis C. METHODS: Thirty-eight HCV mono-infected and 87 HCV/HBV co-infected patients constituted this study. Western-blot and ELISA were used for identifying HCV-NS4, hepatitis B surface antigen (HBsAg), collagen III and matrixmetalloproteinase-1 (MMP-1) in patients' sera...
April 2017: British Journal of Biomedical Science
https://www.readbyqxmd.com/read/28343379/hepatitis-c-virus-nonstructural-5a-protein-hcv-ns5a-inhibits-hepatocyte-apoptosis-through-the-nf-%C3%AE%C2%BAb-mir-503-bcl-2-pathway
#4
Zhengyuan Xie, Zhihua Xiao, Fenfen Wang
The nonstructural protein 5A (NS5A) encoded by the human hepatitis C virus (HCV) RNA genome is a multifunctional phosphoprotein. To analyse the influence of NS5A on apoptosis, we established an Hep-NS5A cell line (HepG2 cells that stably express NS5A) and induced apoptosis using tumour necrosis factor (TNF)-α. We utilised the MTT assay to detect cell viability, real-time quantitative polymerase chain reaction and Western blot to analyse gene and protein expression, and a luciferase reporter gene experiment to investigate the targeted regulatory relationship...
March 2017: Molecules and Cells
https://www.readbyqxmd.com/read/28283039/hepatitis-c-virus-ns3-protein-enhances-hepatocellular-carcinoma-cell-invasion-by-promoting-ppm1a-ubiquitination-and-degradation
#5
Yali Zhou, Yan Zhao, Yaoying Gao, Wenjun Hu, Yan Qu, Ning Lou, Ying Zhu, Xiaoping Zhang, Hongmei Yang
BACKGROUND: Growing evidence suggests that hepatitis C virus (HCV) contributes to hepatocellular carcinoma (HCC) by directly modulating oncogenic signaling pathways. Protein phosphatase magnesium-dependent 1A (PPM1A) has recently emerged as an important tumor suppressor as it can block a range of tumor-centric signaling pathways through protein dephosphorylation. However, the role and regulatory mechanisms of PPM1A in HCV-infected cells have not been reported. METHODS: Total, cytoplasmic, and nuclear PPM1A protein after HCV infection or overexpression of HCV nonstructural protein 3 (NS3) were detected by western blotting...
March 10, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28260862/sofosbuvir-velpatasvir-regimen-promises-an-effective-pan-genotypic-hepatitis-c-virus-cure
#6
REVIEW
Fazia Mir, Alp S Kahveci, Jamal A Ibdah, Veysel Tahan
Hepatitis C virus (HCV) is a global pandemic, with nearly 200 million infected patients worldwide. HCV is the most common blood-borne infection in the US with numerous health implications including liver fibrosis, cirrhosis, and hepatocellular cancer. Traditional genotype-based HCV therapies with interferon resulted in moderate success in the sustained elimination of viral genome. Recent clinical trials of the once-daily combination tablet of sofosbuvir, a nonstructural (NS) 5B polymerase inhibitor, and velpatasvir, an NS5A inhibitor, demonstrate sustained virologic response rates of about 95%, regardless of prior treatment experience or presence of cirrhosis across all HCV genotypes...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28258380/clinical-pharmacokinetics-of-dasabuvir
#7
REVIEW
Jennifer R King, Jiuhong Zha, Amit Khatri, Sandeep Dutta, Rajeev M Menon
Dasabuvir is a nonstructural (NS) 5B non-nucleoside inhibitor of the hepatitis C virus (HCV) used in combination with ombitasvir/paritaprevir/ritonavir for the treatment of chronic HCV infection. It is primarily metabolized by cytochrome P450 (CYP) 2C8, with a minor contribution from CYP3A. Biotransformation of dasabuvir forms the M1 metabolite, which retains antiviral activity. Dasabuvir exhibits linear pharmacokinetics with a terminal half-life of approximately 5-8 h, allowing for twice-daily dosing. The M1 metabolite of dasabuvir is the major metabolite in plasma and has a half-life similar to that of dasabuvir...
March 4, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28245093/novel-nucleoside-analogues-targeting-hcv-replication-through-an-ns5a-dependent-inhibition-mechanism
#8
Nikolaos Lougiakis, Efseveia Frakolaki, Panagiota Karmou, Nicole Pouli, Panagiotis Marakos, Vanesa Madan, Ralf Bartenschlager, Niki Vassilaki
A series of new tricyclic nucleosides were synthesized and evaluated as Hepatitis C virus (HCV) replication inhibitors. Initial screening in a HCV replicon system, derived from a genotype 1b isolate, identified 9-benzylamino-3-(β-D-ribofuranosyl)-3H-imidazo[4',5':5,6]pyrido[2,3-b]pyrazine (15d) as the most potent analogue. Comparative assessment of 15d activity against HCV full-length viruses or subgenomic replicons derived from genotype 1 - 4 revealed a specificity of the compound for genotypes 1 and 3. Surprisingly, resistance mutations selected against 15d were mapped to domains II and III of the nonstructural protein 5A (NS5A), but not to the RNA-dependent RNA polymerase residing in NS5B...
February 28, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28236252/clinical-pharmacokinetics-of-paritaprevir
#9
REVIEW
Rajeev M Menon, Akshanth R Polepally, Amit Khatri, Walid M Awni, Sandeep Dutta
Paritaprevir is a potent hepatitis C virus (HCV) nonstructural (NS) protein 3/4A protease inhibitor that is used in combination with other direct-acting antivirals (DAAs) for the treatment of chronic HCV infection. Paritaprevir is primarily metabolized by cytochrome P450 (CYP) 3A4 and is administered with a low dose of ritonavir to achieve drug concentrations suitable for once-daily dosing. Coadministration of paritaprevir with ritonavir increases the half-life of single-dose paritaprevir from approximately 3 h to 5-8 h, doubles the time to maximum plasma concentration (T max) from 2...
February 25, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28229375/clinical-pharmacokinetics-of-ombitasvir
#10
REVIEW
Prajakta S Badri, Diana L Shuster, Sandeep Dutta, Rajeev M Menon
Ombitasvir is a potent, nonstructural protein 5A inhibitor of the hepatitis C virus (HCV) that is used in combination with other direct-acting antivirals for the treatment of chronic HCV infection. Ombitasvir is predominantly metabolized by amide hydrolysis followed by oxidative metabolism and is a substrate of P-glycoprotein. Ombitasvir displays linear pharmacokinetics with minimal accumulation and is eliminated via metabolism and biliary excretion. A negligible amount of unchanged drug is excreted in urine...
February 22, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28193518/safety-and-efficacy-of-elbasvir-grazoprevir-in-patients-with%C3%A2-hepatitis-c-virus-infection-and-compensated-cirrhosis-an%C3%A2-integrated-analysis
#11
Ira M Jacobson, Eric Lawitz, Paul Y Kwo, Christophe Hézode, Cheng-Yuan Peng, Anita Y M Howe, Peggy Hwang, Janice Wahl, Michael Robertson, Eliav Barr, Barbara A Haber
BACKGROUND & AIMS: Persons with hepatitis C virus (HCV) infection are at risk of progressive liver disease, cirrhosis, and decompensation. We analyzed the effects of the direct-acting antiviral agents elbasvir and grazoprevir in patients with HCV infection and compensated cirrhosis, combining data from 6 clinical trials. METHODS: We performed an integrated analysis of 402 patients with HCV genotype 1, 4, or 6 infection and Child-Pugh A compensated cirrhosis enrolled in 6 clinical trials...
February 11, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28164628/evaluation-of-truncated-hcv-ns3-protein-for-potential-applications-in-immunization-and-diagnosis
#12
Foozieh Javadi, Pooneh Rahimi, Mohammad Hossien Modarressi, Azam Bolhassani, Mehdi Shafiee Ardestani, Seyed Mehdi Sadat, Mohammad Reza Aghasadeghi
BACKGROUND: Hepatitis C virus infection is one of global health concern. No vaccine is available so far and nonstructural protein 3 (NS3) is one of the main target antigens for developing studies on therapeutic vaccine and diagnostic application. In the current study, we expressed a truncated recombinant HCV-NS3 protein under native condition and evaluated its potential applications in immunization and diagnosis. METHODS: The recombinant pET-NS3 containing a truncated form of HCV NS3 region was constructed, confirmed by sequencing reactions, and expressed into E...
July 1, 2016: Clinical Laboratory
https://www.readbyqxmd.com/read/28112593/oral-combination-vaccine-comprising-bifidobacterium-displaying-hepatitis-c-virus-nonstructural-protein-3-and-interferon-%C3%AE-induces-strong-cellular-immunity-specific-to-nonstructural-protein-3-in-mice
#13
Koichi Kitagawa, Chika Omoto, Tsugumi Oda, Ayame Araki, Hiroki Saito, Katsumi Shigemura, Takane Katayama, Hak Hotta, Toshiro Shirakawa
We previously generated an oral hepatitis C virus (HCV) vaccine using Bifidobacterium displaying the HCV nonstructural protein 3 (NS3) polypeptide. NS3-specific cellular immunity is important for viral clearance and recovery from HCV infection. In this study, we enhanced the cellular immune responses induced by our oral HCV vaccine, Bifidobacterium longum 2165 (B. longum 2165), by combining interferon-α (IFN-α) as an adjuvant with the vaccine in a mouse experimental model. IFN-α is a widely used cytokine meeting the standard of care (SOC) for HCV infection and plays various immunoregulatory roles...
April 2017: Viral Immunology
https://www.readbyqxmd.com/read/28107512/nonstructural-5a-protein-of-hepatitis-c-virus-interferes-with-toll-like-receptor-signaling-and-suppresses-the-interferon-response-in-mouse-liver
#14
Takeya Tsutsumi, Kazuya Okushin, Kenichiro Enooku, Hidetaka Fujinaga, Kyoji Moriya, Hiroshi Yotsuyanagi, Hideki Aizaki, Tetsuro Suzuki, Yoshiharu Matsuura, Kazuhiko Koike
The hepatitis C virus nonstructural protein NS5A is involved in resistance to the host immune response, as well as the viral lifecycle such as replication and maturation. Here, we established transgenic mice expressing NS5A protein in the liver and examined innate immune responses against lipopolysaccharide (LPS) in vivo. Intrahepatic gene expression levels of cytokines such as interleukin-6, tumor necrosis factor-α, and interferon-γ were significantly suppressed after LPS injection in the transgenic mouse liver...
2017: PloS One
https://www.readbyqxmd.com/read/28106726/discrepancy-between-hepatitis-c-virus-genotypes-and-ns4-based-serotypes-association-with-their-subgenomic-sequences
#15
Nan Nwe Win, Shingo Nakamoto, Tatsuo Kanda, Hiroki Takahashi, Azusa Takahashi-Nakaguchi, Shin Yasui, Masato Nakamura, Shuang Wu, Fumio Imazeki, Shigeru Mikami, Osamu Yokosuka, Tohru Gonoi, Hiroshi Shirasawa
Determination of hepatitis C virus (HCV) genotypes plays an important role in the direct-acting agent era. Discrepancies between HCV genotyping and serotyping assays are occasionally observed. Eighteen samples with discrepant results between genotyping and serotyping methods were analyzed. HCV serotyping and genotyping were based on the HCV nonstructural 4 (NS4) region and 5'-untranslated region (5'-UTR), respectively. HCV core and NS4 regions were chosen to be sequenced and were compared with the genotyping and serotyping results...
January 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28067309/the-autophagy-elongation-complex-atg5-12-16l1-positively-regulates-hcv-replication-and-is-required-for-wild-type-membranous-web-formation
#16
Ahmed M Fahmy, Patrick Labonté
Hepatitis C virus (HCV) infection induces intracellular membrane rearrangements, thus forming a membranous web (MW) in which HCV replication and assembly occur. The HCV-induced MW is primarily composed of double membrane vesicles (DMVs) transfused by multi-membrane vesicles. The autophagy machinery has been proposed to participate in the formation of such vesicles. However, no clear evidence has been found linking autophagy to the formation of these DMVs. In this study, we evaluated the role of the autophagy elongation complex (ATG5-12/16L1) in HCV replication and MW formation...
January 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28035485/action-and-function-of-wnt-%C3%AE-catenin-signaling-in-the-progression-from-chronic-hepatitis-c-to-hepatocellular-carcinoma
#17
REVIEW
Wenhui Wang, Qiuwei Pan, Gwenny M Fuhler, Ron Smits, Maikel P Peppelenbosch
Hepatitis C virus (HCV) infection is one of the leading causes of hepatocellular carcinoma (HCC) worldwide but the mechanistic basis as to how chronic HCV infection furthers the HCC process remains only poorly understood. Accumulating evidence indicates that HCV core and nonstructural proteins provoke activation of the Wnt/β-catenin signaling pathway, and the evidence supporting a role of Wnt/β-catenin signaling in the onset and progression of HCC is compelling. Convincing molecular explanations as to how expression of viral effectors translates into increased activity of the Wnt/β-catenin signaling machinery are still largely lacking, hampering the design of rational strategies aimed at preventing HCC...
April 2017: Journal of Gastroenterology
https://www.readbyqxmd.com/read/27898592/the-hepatitis-c-virus-nonstructural-protein-3-q80k-polymorphism-is-frequently-detected-and-transmitted-among-hiv-infected-msm-in-the-netherlands
#18
Astrid M Newsum, Cynthia K Y Ho, Faydra I Lieveld, Thijs J W van de Laar, Sylvie M Koekkoek, Sjoerd P Rebers, Jan T M van der Meer, Anne M J Wensing, Greet J Boland, Joop E Arends, Karel J van Erpecum, Maria Prins, Richard Molenkamp, Janke Schinkel
OBJECTIVES: The Q80K polymorphism is a naturally occurring resistance-associated variant in the hepatitis C virus (HCV) nonstructural protein 3 (NS3) region and is likely transmissible between hosts. This study describes the Q80K origin and prevalence among HCV risk groups in the Netherlands and examines whether Q80K is linked to specific transmission networks. DESIGN AND METHODS: Stored blood samples from HCV genotype 1a-infected patients were used for PCR and sequencing to reconstruct the NS3 maximum likelihood phylogeny...
January 2, 2017: AIDS
https://www.readbyqxmd.com/read/27808515/the-discovery-of-ruzasvir-mk-8408-a-potent-pan-genotype-hcv-ns5a-inhibitor-with-optimized-activity-against-common-resistance-associated-polymorphisms
#19
Ling Tong, Wensheng Yu, Lei Chen, Oleg Selyutin, Michael P Dwyer, Anilkumar Gopinadhan Nair, Robert Mazzola, Jae-Hun Kim, Deyou Sha, Jingjun Yin, Rebecca Tamra Ruck, Ian W Davies, Bin Hu, Bin Zhong, Jinglai Hao, Tao Ji, Shuai Zan, Rong Liu, Sony Agrawal, Ellen Xia, Stephanie Curry, Patricia Mcmonagle, Karin Bystol, Frederick Lahser, Donna Carr, Laura Rokosz, Paul Ingravallo, Shiying Chen, Kung-I Feng, Mark Cartwright, Ernest Asante-Appiah, Joseph A Kozlowski
We describe the research that led to the discovery of compound 40 (ruzasvir, MK-8408), a pan-genotypic HCV nonstructural protein 5A (NS5A) inhibitor with a "flat" GT1 mutant profile. This NS5A inhibitor contains a unique tetracyclic indole core, while maintaining the imidazole-proline-valine Moc motifs of our previous NS5A inhibitors. Compound 40 is currently in early clinical trials and is under evaluation as part of an all-oral DAA regimen for the treatment of chronic HCV infection..
November 3, 2016: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27803188/hepatitis-c-virus-proteins-interact-with-the-endosomal-sorting-complex-required-for-transport-escrt-machinery-via-ubiquitination-to-facilitate-viral-envelopment
#20
Rina Barouch-Bentov, Gregory Neveu, Fei Xiao, Melanie Beer, Elena Bekerman, Stanford Schor, Joseph Campbell, Jim Boonyaratanakornkit, Brett Lindenbach, Albert Lu, Yves Jacob, Shirit Einav
Enveloped viruses commonly utilize late-domain motifs, sometimes cooperatively with ubiquitin, to hijack the endosomal sorting complex required for transport (ESCRT) machinery for budding at the plasma membrane. However, the mechanisms underlying budding of viruses lacking defined late-domain motifs and budding into intracellular compartments are poorly characterized. Here, we map a network of hepatitis C virus (HCV) protein interactions with the ESCRT machinery using a mammalian-cell-based protein interaction screen and reveal nine novel interactions...
November 1, 2016: MBio
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