Effective epitope identification employing phylogenetic, mutational variability, sequence entropy, and correlated mutation analysis targeting NS5B protein of hepatitis C virus: from bioinformatics to therapeutics

2015 ◽  
Vol 28 (8) ◽  
pp. 492-505
Author(s):  
Rohan J. Meshram ◽  
Rajesh N. Gacche
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Mutation Analysis ◽  
Sequence Entropy ◽  
Epitope Identification ◽  
Correlated Mutation ◽  
Ns5b Protein

Hybrid K-means, fuzzy C-means, and hierarchical clustering for DNA hepatitis C virus trend mutation analysis

2019 ◽  
Vol 121 ◽  
pp. 373-381 ◽  
Author(s):  
Berlian Al Kindhi ◽  
Tri Arief Sardjono ◽  
Mauridhi Hery Purnomo ◽  
Gijbertus Jacob Verkerke
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Hierarchical Clustering ◽  
Mutation Analysis ◽  
Fuzzy C Means

scholarly journals Ribonucleotide reductase M2 promotes RNA replication of hepatitis C virus by protecting NS5B protein from hPLIC1-dependent proteasomal degradation

2019 ◽  
Vol 294 (15) ◽  
pp. 5759-5773 ◽  
Author(s):  
Bouchra Kitab ◽  
Masaaki Satoh ◽  
Yusuke Ohmori ◽  
Tsubasa Munakata ◽  
Masayuki Sudoh ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Ribonucleotide Reductase ◽  
Rna Replication ◽  
Proteasomal Degradation ◽  
Ns5b Protein

scholarly journals Hepatitis C Virus RNA-Dependent RNA Polymerase Is Regulated by Cysteine S-Glutathionylation

2019 ◽  
Vol 2019 ◽  
pp. 1-11
Author(s):  
Marina K. Kukhanova ◽  
Vera L. Tunitskaya ◽  
Olga A. Smirnova ◽  
Olga A. Khomich ◽  
Natalia F. Zakirova ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Recombinant Protein ◽  
Rna Polymerase ◽  
Reducing Agents ◽  
Cysteine Residues ◽  
Rdrp Activity ◽  
Rna Dependent Rna Polymerase ◽  
Redox Switches ◽  
Ns5b Protein

Hepatitis C virus (HCV) triggers massive production of reactive oxygen species (ROS) and affects expression of genes encoding ROS-scavenging enzymes. Multiple lines of evidence show that levels of ROS production contribute to the development of various virus-associated pathologies. However, investigation of HCV redox biology so far remained in the paradigm of oxidative stress, whereas no attention was given to the identification of redox switches among viral proteins. Here, we report that one of such redox switches is the NS5B protein that exhibits RNA-dependent RNA polymerase (RdRp) activity. Treatment of the recombinant protein with reducing agents significantly increases its enzymatic activity. Moreover, we show that the NS5B protein is subjected to S-glutathionylation that affects cysteine residues 89, 140, 170, 223, 274, 521, and either 279 or 295. Substitution of these cysteines except C89 and C223 with serine residues led to the reduction of the RdRp activity of the recombinant protein in a primer-dependent assay. The recombinant protein with a C279S mutation was almost inactive in vitro and could not be activated with reducing agents. In contrast, cysteine substitutions in the NS5B region in the context of a subgenomic replicon displayed opposite effects: most of the mutations enhanced HCV replication. This difference may be explained by the deleterious effect of oxidation of NS5B cysteine residues in liver cells and by the protective role of S-glutathionylation. Based on these data, redox-sensitive posttranslational modifications of HCV NS5B and other proteins merit a more detailed investigation and analysis of their role(s) in the virus life cycle and associated pathogenesis.

scholarly journals Pharmacokinetics of a Cholesterol-conjugated Aptamer Against the Hepatitis C Virus (HCV) NS5B Protein

2015 ◽  
Vol 4 ◽  
pp. e254 ◽  
Author(s):  
Chang Ho Lee ◽  
Soo-Han Lee ◽  
Ji Hyun Kim ◽  
Yook-Hwan Noh ◽  
Gyu-Jeong Noh ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Hcv Ns5b ◽  
Ns5b Protein

scholarly journals Hepatitis C Virus Nonstructural 5B Protein Regulates Tumor Necrosis Factor Alpha Signaling through Effects on Cellular IκB Kinase

2006 ◽  
Vol 26 (8) ◽  
pp. 3048-3059 ◽  
Author(s):  
Soo-Ho Choi ◽  
Kyu-Jin Park ◽  
Byung-Yoon Ahn ◽  
Guhung Jung ◽  
Michael M. C. Lai ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Necrosis Factor Alpha ◽  
Hepatic Cells ◽  
Tnf Α ◽  
Factor Alpha ◽  
Ns5b Protein ◽  
Necrosis Factor

ABSTRACT Hepatitis C virus (HCV) NS5B protein is a membrane-associated phosphoprotein that possesses an RNA-dependent RNA polymerase activity. We recently reported that NS5A protein interacts with TRAF2 and modulates tumor necrosis factor alpha (TNF-α)-induced NF-κB and Jun N-terminal protein kinase (JNK). Since NS5A and NS5B are the essential components of the HCV replication complex, we examined whether NS5B could modulate TNF-α-induced NF-κB and JNK activation. In this study, we have demonstrated that TNF-α-induced NF-κB activation is inhibited by NS5B protein in HEK293 and hepatic cells. Furthermore, NS5B protein inhibited both TRAF2- and IKK-induced NF-κB activation. Using coimmunoprecipitation assays, we show that NS5B interacts with IKKα. Most importantly, NS5B protein in HCV subgenomic replicon cells interacted with endogenous IKKα, and then TNF-α-mediated IKKα kinase activation was significantly decreased by NS5B. Using in vitro kinase assay, we have further found that NS5B protein synergistically activated TNF-α-mediated JNK activity in HEK293 and hepatic cells. These data suggest that NS5B protein modulates TNF-α signaling pathways and may contribute to HCV pathogenesis.

scholarly journals Hepatitis C Virus NS5B Protein Is a Membrane-Associated Phosphoprotein with a Predominantly Perinuclear Localization

Virology ◽  
1997 ◽  
Vol 227 (2) ◽  
pp. 439-446 ◽  
Author(s):  
Soon B. Hwang ◽  
Kyu-Jin Park ◽  
Yong-Sun Kim ◽  
Young Chul Sung ◽  
Michael M.C. Lai
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Ns5b Protein

scholarly journals Chaperonin TRiC/CCT participates in replication of hepatitis C virus genome via interaction with the viral NS5B protein

Virology ◽  
2011 ◽  
Vol 410 (1) ◽  
pp. 38-47 ◽  
Author(s):  
Yasushi Inoue ◽  
Hideki Aizaki ◽  
Hiromichi Hara ◽  
Mami Matsuda ◽  
Tomomi Ando ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Virus Genome ◽  
Ns5b Protein

scholarly journals Diversity of Hepatitis C Virus Quasispecies Evaluated by Denaturing Gradient Gel Electrophoresis

2001 ◽  
Vol 8 (1) ◽  
pp. 62-73 ◽  
Author(s):  
K. A. Harris ◽  
C. G. Teo
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Gel Electrophoresis ◽  
Drug Users ◽  
Denaturing Gradient Gel Electrophoresis ◽  
Hypervariable Region ◽  
Serum Samples ◽  
Sequence Entropy ◽  
Gradient Gel Electrophoresis ◽  
Antibody Levels

ABSTRACT Denaturing gradient gel electrophoresis (DGGE) was used to study the diversity of hepatitis C virus (HCV) quasispecies. Optimized DGGE running conditions were applied to screen for variations in sequences cloned from amplicons originating from the nonstructural 5b (NS5b) gene of HCV in blood of hemophilia patients, intravenous drug users, and blood donors (five specimens from each study group, ca. 40 clones studied per specimen). Clones identified by DGGE as unique were sequenced. NS5b sequence entropy and mean genetic distance in hemophiliacs did not differ significantly from those in the other groups, pointing to a lack of correlation between HCV diversity and the multiplicity of past HCV exposures. DGGE was also applied to investigate variation in the HCV envelope 2/hypervariable region 1 (E2/HVR-1) in serum samples serially taken from two patients during the seroconversion phase of HCV infection. E2/HVR-1 sequence entropy changes were small and not correlated with rising anti-HCV antibody levels, reflecting mutational changes not mediated by antibody selection.

scholarly journals Antiviral effects of the interferon-induced protein guanylate binding protein 1 and its interaction with the hepatitis C virus NS5B protein

Hepatology ◽  
2009 ◽  
Vol 50 (6) ◽  
pp. 1727-1737 ◽  
Author(s):  
Yasuhiro Itsui ◽  
Naoya Sakamoto ◽  
Sei Kakinuma ◽  
Mina Nakagawa ◽  
Yuko Sekine-Osajima ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Binding Protein ◽  
Antiviral Effects ◽  
Ns5b Protein ◽  
Guanylate Binding Protein

Polymorphisms of NS5B protein relates to early clearance of hepatitis C virus by interferon plus ribavirin: a pilot study

2004 ◽  
Vol 11 (3) ◽  
pp. 225-235 ◽  
Author(s):  
N. Kumagai ◽  
N. Takahashi ◽  
M. Kinoshita ◽  
S. Tsunematsu ◽  
K. Tsuchimoto ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Pilot Study ◽  
Ns5b Protein
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