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Hepatitis C Virus NS4B

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https://www.readbyqxmd.com/read/29599605/cell-culture-adaptive-mutations-in-hepatitis-c-virus-promote-viral-production-by-enhancing-viral-replication-and-release
#1
Qi Wang, Yue Li, Shun-Ai Liu, Wen Xie, Jun Cheng
AIM: To explore hepatitis C virus (HCV) adaptive mutations or combinations thereof responsible for enhanced viral production and investigate the underlying mechanisms. METHODS: A series of plasmids with adaptive mutations were constructed. After the plasmids were transfected into Huh7.5 cells, we determined the infectious HCV particle titers by NS5A immunofluorescence assays, and detected HCV RNA replication by real-time PCR and protein expression by Western blot...
March 28, 2018: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/29516328/persistence-of-circulating-hepatitis-c-virus-antigens-specific-immune-complexes-in-patients-with-resolved-hcv-infection
#2
Ke-Qin Hu, Wei Cui
BACKGROUND: Our recent study indicated the possible presence of detectable hepatitis C virus antigens (HCV-Ags) after denaturation of sera with resolved HCV (R-HCV) infection. The present study determined and characterized persistent HCV-Ags-specific immune complexes (ICs) in these patients. METHODS: Sixty-eight sera with R-HCV and 34 with viremic HCV (V-HCV) infection were tested for free and IC-bound HCV-Ags using HCV-Ags enzyme immunoassay (EIA), the presence of HCV-Ags-specific ICs by immunoprecipitation and Western blot (IP-WB), HCV ICs containing HCV virions using IP and HCV RNA RT-PCR, and correlation of HCV ICs with clinical presentation in these patients...
March 8, 2018: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/29397939/hepatitis-c-virus-regulates-proprotein-convertase-subtilisin-kexin-type-9-promoter-activity
#3
Zhubing Li, Qiang Liu
Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a secretory serine protease mainly expressed in liver. Although PCSK9 has been shown to inhibit hepatitis C virus (HCV) entry and replication, whether HCV regulates PCSK9 transcription has not been well studied. PCSK9 promoter activity is modulated by numerous transcription factors including sterol-regulatory element binding protein (SREBP)-1a, -1c, -2, hepatocyte nuclear factor-1 (HNF-1), and forkhead box O3 (FoxO3). Since they are differently regulated by HCV, we studied the effects of these transcription factors on PCSK9 promoter activity in the context of HCV infection and replication...
January 31, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29295958/correction-for-yi-et-al-hepatitis-c-virus-ns4b-can-suppress-sting-accumulation-to-evade-innate-immune-responses
#4
Guanghui Yi, Yahong Wen, Chang Shu, Qingxia Han, Kouacou V Konan, Pingwei Li, C Cheng Kao
No abstract text is available yet for this article.
January 15, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29182667/heat-shock-proteins-hspb8-and-dnajc5b-have-hcv-antiviral-activity
#5
Ana Claudia Silva Braga, Bruno Moreira Carneiro, Mariana Nogueira Batista, Mônica Mayumi Akinaga, Cíntia Bittar, Paula Rahal
Hepatitis C is a disease caused by the hepatitis C virus (HCV), and an estimated 3% of the world population is infected with the virus. During replication, HCV interacts with several cellular proteins. Studies have shown that several heat shock proteins (HSPs) have an altered expression profile in the presence of the virus, and some HSPs interact directly with HCV proteins. In the present study, we evaluated the expression levels of heat shock proteins in vitro in the presence and absence of HCV. The differential expression of 84 HSPs and chaperones was observed using a qPCR array, comparing HCV uninfected and infected Huh7...
2017: PloS One
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
#6
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/29037976/characterization-of-a-dengue-ns4b-inhibitor-originating-from-an-hcv-small-molecule-library
#7
Ilane Hernandez-Morales, Peggy Geluykens, Marleen Clynhens, Rudy Strijbos, Olivia Goethals, Sarah Megens, Nick Verheyen, Stefaan Last, David McGowan, Erwin Coesemans, Benoît De Boeck, Bart Stoops, Benoit Devogelaere, Frederik Pauwels, Koen Vandyck, Jan Martin Berke, Pierre Raboisson, Kenneth Simmen, Pedro Lory, Marnix Van Loock
Dengue is the most important mosquito-transmitted viral disease and a major global health concern. Over the last decade, dengue virus (DENV) drug discovery and development has intensified, however, this has not resulted in approved DENV-specific antiviral treatments yet. DENV and hepatitis C virus (HCV) belong to the same Flaviviridae family and, in contrast to DENV, antiviral treatments for HCV have been licensed. Therefore, applying the knowledge gained on anti-HCV drugs may foster the discovery and development of dengue antiviral drugs...
October 14, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28991176/innate-immune-evasion-mediated-by-flaviviridae-non-structural-proteins
#8
REVIEW
Shun Chen, Zhen Wu, Mingshu Wang, Anchun Cheng
Flaviviridae-caused diseases are a critical, emerging public health problem worldwide. Flaviviridae infections usually cause severe, acute or chronic diseases, such as liver damage and liver cancer resulting from a hepatitis C virus (HCV) infection and high fever and shock caused by yellow fever. Many researchers worldwide are investigating the mechanisms by which Flaviviridae cause severe diseases. Flaviviridae can interfere with the host's innate immunity to achieve their purpose of proliferation. For instance, dengue virus (DENV) NS2A, NS2B3, NS4A, NS4B and NS5; HCV NS2, NS3, NS3/4A, NS4B and NS5A; and West Nile virus (WNV) NS1 and NS4B proteins are involved in immune evasion...
October 7, 2017: Viruses
https://www.readbyqxmd.com/read/28743875/hepatitis-c-virus-exploits-death-receptor-6-mediated-signaling-pathway-to-facilitate-viral-propagation
#9
Trang T D Luong, Giao V Q Tran, Dong-Jo Shin, Yun-Sook Lim, Soon B Hwang
The life cycle of hepatitis C virus (HCV) is highly dependent on host proteins for virus propagation. By transcriptome sequencing analysis, we identified host genes that were highly differentially expressed in HCV-infected cells. Of these candidates, we selected Death receptor 6 (DR6) for further characterization. DR6 is an orphan member of the tumor necrosis factor receptor superfamily. In the present study, we demonstrated that both mRNA and protein levels of DR6 were increased in the context of HCV replication...
July 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28727784/an-ns5a-single-optimized-method-to-determine-genotype-subtype-and-resistance-profiles-of-hepatitis-c-strains
#10
Elisabeth Andre-Garnier, Bernard Besse, Audrey Rodallec, Olivier Ribeyrol, Virginie Ferre, Caroline Luco, Laura Le Guen, Nathalie Bourgeois, Jérôme Gournay, Eric Billaud, François Raffi, Marianne Coste-Burel, Berthe-Marie Imbert-Marcille
The objective was to develop a method of HCV genome sequencing that allowed simultaneous genotyping and NS5A inhibitor resistance profiling. In order to validate the use of a unique RT-PCR for genotypes 1-5, 142 plasma samples from patients infected with HCV were analysed. The NS4B-NS5A partial region was successfully amplified and sequenced in all samples. In parallel, partial NS3 sequences were analyzed obtained for genotyping. Phylogenetic analysis showed concordance of genotypes and subtypes with a bootstrap >95% for each type cluster...
2017: PloS One
https://www.readbyqxmd.com/read/28588082/ire1%C3%AE-promotes-viral-infection-by-conferring-resistance-to-apoptosis
#11
Susan L Fink, Teshika R Jayewickreme, Ryan D Molony, Takao Iwawaki, Charles S Landis, Brett D Lindenbach, Akiko Iwasaki
The unfolded protein response (UPR) is an ancient cellular pathway that detects and alleviates protein-folding stresses. The UPR components X-box binding protein 1 (XBP1) and inositol-requiring enzyme 1α (IRE1α) promote type I interferon (IFN) responses. We found that Xbp1 -deficient mouse embryonic fibroblasts and macrophages had impaired antiviral resistance. However, this was not because of a defect in type I IFN responses but rather an inability of Xbp1 -deficient cells to undergo viral-induced apoptosis...
June 6, 2017: Science Signaling
https://www.readbyqxmd.com/read/28551625/intrahepatic-hcv-rna-level-and-genotype-1-independently-associate-with-hepatic-reticulon-3-expression
#12
Chih-Lang Lin, Rong-Nan Chien, Kung-Hao Liang, Po-Yuan Ke, Ya-Hui Huang, Chau-Ting Yeh
Background /Aim: Reticulon 3 (RTN3), resides predominantly in the endoplasmic reticulum and has opposite regulatory effects on Hepatitis C virus (HCV) replication through interacting with NS5A and NS4B proteins. This study aimed to unravel the actual effect of RTN3 on HCV replication. MATERIALS AND METHODS: A total of 115 HCV-related hepatocellular carcinoma patients receiving hepatectomy was enrolled in this study. The hepatic HCV RNA and RTN3 protein levels in the non-cancerous liver tissues were examined for clinical analysis...
June 2017: Anticancer Research
https://www.readbyqxmd.com/read/28545480/effects-of-hepatitis-c-virus-core-protein-and-nonstructural-protein-4b-on-the-wnt-%C3%AE-catenin-pathway
#13
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/28431572/hepatitis-c-virus-ns4b-protein-induces-epithelial-mesenchymal-transition-by-upregulation-of-snail
#14
Bicheng Hu, Shenggao Xie, Yuqian Hu, Wen Chen, Xiaofan Chen, Yi Zheng, Xinxing Wu
BACKGROUND: Chronic hepatitis C virus (HCV) infection is an important cause of hepatocellular carcinoma (HCC). Epithelial to mesenchymal transition (EMT) is a key process associated with tumor metastasis and poor prognosis. HCV infection, HCV core and NS5A protein could induce EMT process, but the role of NS4B on EMT remains poorly understood. METHODS: We overexpressed HCV NS4B protein in HepG2 cells or Huh7.5.1 cells infected by HCVcc, the E-cadherin expression, N-cadherin expression and the EMT-associated transcriptional factor Snail were determined...
April 21, 2017: Virology Journal
https://www.readbyqxmd.com/read/28170421/comprehensive-mapping-of-antigen-specific-t-cell-responses-in-hepatitis-c-virus-infected-patients-with-or-without-spontaneous-viral-clearance
#15
Chao Zhang, Rui Hua, Yuanyuan Cui, Shasha Wang, Hongqing Yan, Dongmei Li, Yonghong Zhang, Zhengkun Tu, Pei Hao, Xinyue Chen, Jin Zhong, Junqi Niu, Xia Jin
Elucidating protective immunity against HCV is important for the development of a preventative vaccine. We hypothesize that spontaneous resolution of acute HCV infection offers clue to protective immune responses, and that DAA therapy affects the quality and quantity of HCV-specific T cell responses. To test these hypotheses, we performed T cell epitope mapping in 111 HCV-infected individuals including 61 chronically HCV-1b (CHC-1b) infected, 24 chronically HCV-2a (CHC-2a) infected and 26 spontaneously recovered (SPR) patients with 376 overlapping peptides covering the entire HCV polyprotein...
2017: PloS One
https://www.readbyqxmd.com/read/27932311/daclatasvir-prevents-hepatitis-c-virus-infectivity-by-blocking-transfer-of-the-viral-genome-to-assembly-sites
#16
Bertrand Boson, Solène Denolly, Fanny Turlure, Christophe Chamot, Marlène Dreux, François-Loïc Cosset
BACKGROUND & AIMS: Daclatasvir is a direct-acting antiviral agent and potent inhibitor of NS5A, which is involved in replication of the hepatitis C virus (HCV) genome, presumably via membranous web shaping, and assembly of new virions, likely via transfer of the HCV RNA genome to viral particle assembly sites. Daclatasvir inhibits the formation of new membranous web structures and, ultimately, of replication complex vesicles, but also inhibits an early assembly step. We investigated the relationship between daclatasvir-induced clustering of HCV proteins, intracellular localization of viral RNAs, and inhibition of viral particle assembly...
March 2017: Gastroenterology
https://www.readbyqxmd.com/read/27923769/recombination-in-hepatitis-c-virus-is-not-uncommon-among-people-who-inject-drugs-in-kolkata-india
#17
Debanjali Gupta, Kallol Saha, Aritra Biswas, Rushna Firdaus, Monika Ghosh, Provash Chandra Sadhukhan
Recombination in RNA virus is a rare event in the survival and evolution to evade host immune system. This is increasing within high risk group population (HRG) due to super infection that occurs by continuous sharing of common drug equipment by HCV infected or HIV-HCV co-infected recurrent drug users. Recombination causes impediment to vaccine development and therapeutic intervention as standard HCV treatment is still genotype specific. Blood samples of 194 people who inject drugs (PWID) were collected from an Opioid Substitution Therapy Centre in Kolkata, India...
March 2017: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/27678340/production-of-infectious-hcv-genotype-1b-virus-in-cell-culture-using-a-novel-set-of-adaptive-mutations
#18
Ken-Ichi Mori, Akihiro Matsumoto, Noboru Maki, Yuki Ichikawa, Eiji Tanaka, Shintaro Yagi
BACKGROUND: Despite the high prevalence of genotype 1b hepatitis C virus (HCV) among patients, a cell culture system that permits entire viral life cycle of genotype 1b isolates is limited. To develop a cell-cultured hepatitis C virus (HCVcc) of genotype 1b, the proper combination of HCV genomic variants and host cells is essential. HCV genomes isolated from patients with distinctive symptoms may provide the variants required to establish an HCVcc of genotype 1b. RESULTS: We first established subgenomic replicons in Huh7 cells using HCV cDNAs isolated from two patients: one with fulminant hepatitis after liver transplantation (TPF1) and another with acute hepatitis and moderate symptoms (sAH)...
September 27, 2016: BMC Microbiology
https://www.readbyqxmd.com/read/27620477/ptc725-an-ns4b-targeting-compound-inhibits-a-hepatitis-c-virus-genotype-3-replicon-as-predicted-by-genome-sequence-analysis-and-determined-experimentally
#19
Jason D Graci, Stephen P Jung, John Pichardo, Frederick Lahser, Xiao Tong, Zhengxian Gu, Joseph M Colacino
PTC725 is a small molecule NS4B-targeting inhibitor of hepatitis C virus (HCV) genotype (gt) 1 RNA replication that lacks activity against HCV gt2. We analyzed the Los Alamos HCV sequence database to predict susceptible/resistant HCV gt's according to the prevalence of known resistance-conferring amino acids in the NS4B protein. Our analysis predicted that HCV gt3 would be highly susceptible to the activity of PTC725. Indeed, PTC725 was shown to be active against a gt3 subgenomic replicon with a 50% effective concentration of ∼5 nM...
December 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27503576/isolation-and-characterization-of-hepatitis-c-virus-resistant-to-a-novel-phenanthridinone-derivative
#20
Wataru Ito, Masaaki Toyama, Mika Okamoto, Masanori Ikeda, Koichi Watashi, Takaji Wakita, Yuichi Hashimoto, Masanori Baba
BACKGROUND: The novel phenanthridinone derivative HA-719 has recently been identified as a highly potent and selective inhibitor of hepatitis C virus replication. To elucidate its mechanism of inhibition, we have isolated and analyzed a clone of hepatitis C virus replicon cells resistant to HA-719. METHODS: To isolate HA-719-resistant replicon cells, Huh-7 cells containing subgenomic hepatitis C virus replicons (genotype 1b) with a luciferase reporter (LucNeo#2) were cultured in the presence of G418 and escalating concentrations of HA-719...
August 8, 2016: Antiviral Chemistry & Chemotherapy
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