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Author : Chunhong Yin
Publisher :
ISBN 13 :
Total Pages : 230 pages
Book Rating : 4.:/5 (15 download)
Download or read book Functional Analysis of Domain I of the Hepatitis C Virus Non-structural NS5A Protein written by Chunhong Yin and published by . This book was released on 2018 with total page 230 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Structural and Functional Analysis of the Hepatitis C Virus Non-structural Protein 5A. written by and published by . This book was released on 2004 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Das Hepatitis C Virus (HCV) ist ein umhülltes RNA Virus aus der Familie der Flaviviridae. Sein Genom kodiert für ein ca. 3000 Aminosäuren langes Polyprotein, welches co- und posttranslational in seine funktionellen Einheiten gespalten wird. Eines dieser viralen Proteine ist NS5A. Es handelt sich hierbei um ein stark phosphoryliertes Protein, das eine amphipatische α-Helix im Amino-Terminus trägt, welche für die Membran-Assoziation von NS5A verantwortlich ist. Welche Rolle die Phosphorylierung für die Funktion des Proteins spielt, bzw. welche Funktion NS5A überhaupt ausübt, ist zur Zeit noch unklar. Beobachtungen lassen Vermutungen über eine Funktion von NS5A bei der Resistenz infizierter Zellen gegenüber Interferon-alpha zu. Weiterhin wird vermutet, das NS5A als Komponente des membranständigen HCV Replikasekomplexes an der RNA Replikation beteiligt ist. Das Ziel dieser Doktorarbeit war es, die Funktion von NS5A für die RNA Replikation zu untersuchen. Zu diesem Zweck wurde eine Serie von Phosphorylierungsstellen-Mutanten generiert, die auf Ihre Replikationsfähigkeit und den Phosphorylierungsstatus hin untersucht wurden. Wir fanden, dass bestimmte Serin-Substitutionen im Zentrum von NS5A zu einer gesteigerten RNA Replikation führten, bei gleichzeitig reduzierter NS5A Hyperphosphorylierung. Weiterhin studierten wir den Einfluß von Mutationen in der Amino-terminalen amphipatischen α-Helix von NS5A auf die RNA-Replikation, sowie Phosphorylierung und subzelluläre Lokalisation des Proteins. Wir fanden, dass geringfügige strukturelle Veränderungen der amphipatischen Helix zu einer veränderten subzellulären Lokalisation von NS5A führten, was mit einer reduzierten oder komplett inhibierten RNA Replikation einherging. Zudem interferierten die strukturellen Veränderungen mit der Hyperphosphorylierung des Proteins, was den Schluß nahe legt, dass die amphipatische Helix eine wichtige strukturelle Komponente des Proteins darstellt, die für die korrekte Faltung und Phosphorylierung.
Author : Nicole Appel
Publisher :
ISBN 13 :
Total Pages : 20 pages
Book Rating : 4.:/5 (614 download)
Download or read book Structural and Functional Analysis of the Hepatitis C Virus Non-structural Protein 5A written by Nicole Appel and published by . This book was released on 2004 with total page 20 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Functional Analysis of Hepatitis C Virus Non-structural Protein (NS) 3 Protease and Viral Cofactor NS4A. written by and published by . This book was released on 2008 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: The hepatitis C virus (HCV) was identified in 1989 as the major causative agent of transfusion-associated non-A, non-B hepatitis and today represents a worldwide health crisis with prevalence estimates of 2.2%. HCV-specific therapeutics have never been more urgently needed. One of the validated drug targets is the non-structural (NS) protein 3 (NS3) membrane-bound protease. The major aim of this thesis was characterization of NS3 allosteric activation by its viral cofactor, NS4A. We hypothesized that there would be specific residues that dominate the interaction between NS3 and NS4A, and further hypothesized that binding and activation may be separate events mediated by different residues. This thesis details the development of novel cell-based assays for detection of NS3-4A protease activity and heterocomplex formation. The protease assay substrate was a membrane-targeted intracellular protein, which upon proteolysis released a red fluorescent protein (FP) reporter, DsRed-Express, into the cytoplasm; this change was detected by microscopy or quantified by Western blotting. The complex formation assay detected fluorescence resonance energy transfer (FRET) between yellow and cyan FP-tagged NS3 and NS4A, respectively. Our data shows binding can be functionally separated from activation. We identified two NS4A residues (I25 and I29) important for NS3 binding and two NS4A residues (V23 and I25) important for NS3 activation. Therefore the binding-pockets of these residues are prime targets for small-molecule therapeutic development. In addition, I have compared the NS3-4A substrate sequence cleavage efficiencies in vivo. I have been able to show that the activation-dependent NS4B/NS5A junction is processed efficiently and the NS4A/NS4B junction is not. I have also shown NS3-4A substrate specificity is not modulated by replicase components; however the specific activity of this enzyme is increased. The strength of this thesis work stems from the novel and creative develop.
Author : Marianne Ngure
Publisher :
ISBN 13 :
Total Pages : pages
Book Rating : 4.:/5 (11 download)
Download or read book Protein-protein Interactions of the Unstructured Domain II of Hepatitis C Virus NS5A written by Marianne Ngure and published by . This book was released on 2017 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: "The hepatitis C virus (HCV) non-structural 5A (NS5A) protein is a multi-functional, RNA binding protein and an essential component of the HCV replication complex. It is subdivided into 3 domains; a highly structured domain I (DI), while DII and DIII are intrinsically unstructured yet mediate crucial interactions with several viral and cellular host factors. NS5A-DII protein mediates the interaction with Cyclophilin A (CypA), a cellular cis/trans isomerase essential for viral replication. Cyclosporine A (CsA), an inhibitor of CypA, inhibits this interaction and suppresses HCV replication. Mutations that confer resistance to CsA and derivatives have been identified within NS5A-DII (D320E and Y321N in Con 1b). These mutations revive HCV replication in vivo, but the underlying mechanism for resistance remains elusive. Using a Förster Resonance Energy Transfer (FRET)-based approach, we determined a slower rate of dissociation of the resistant NS5A-DII complex with CypA, in the presence of CsA. The slow complex dissociation directly correlated with the increasing level of resistance conferred by either single or double mutations within NS5A-DII. By prolonging the protein-protein complex, D320E and Y321N specifically limit the inhibitory effect of CsA on the NS5A-DII complex with CypA, providing a possible biochemical mechanism of resistance to CypA inhibitors. Apart from its CypA binding properties, NS5A-DII also binds RNA, and interacts with the HCV RNA-dependent RNA polymerase NS5B. However, the largely disordered nature of NS5A-DII has limited the characterization of the structure and functional relevance of these interactions. A mass spectrometry (MS)-assisted foot-printing approach provided an in-depth biochemical characterization of the molecular determinants of protein-protein and nucleoprotein interactions of HCV NS5A-DII with CypA, NS5B and RNA. Overlapping but definitive binding sites for each of the three macromolecules were determined. The conserved residue W316 was identified as a principle mediator of protein-protein interaction (CypA and NS5B) while an arginine-rich region of NS5A-DII was crucial for RNA binding. Specifically, NS5A-DII K308 residue was indispensable for RNA-binding. A novel binding site of NS5A-DII on the NS5B polymerase was mapped predominantly to a region associated with RNA binding. Additionally, binding of NS5A-DII diminished the RNA binding and RNA synthesis activity of NS5B polymerase. This implies a potential regulatory function of NS5A-DII on NS5B polymerase activity. Taken together, this work pinpoints key residues in the intrinsically disordered NS5A-DII that necessitate specific viral and host interactions. NS5A-DII has been plucked from obscurity as we begin to understand the biochemical functional relevance for these interactions, and their significance to HCV replication." --
Author : Vladimir Uversky
Publisher : John Wiley & Sons
ISBN 13 : 0470618310
Total Pages : 532 pages
Book Rating : 4.4/5 (76 download)
Download or read book Flexible Viruses written by Vladimir Uversky and published by John Wiley & Sons. This book was released on 2012-02-07 with total page 532 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book provides up-to-date information on experimental and computational characterization of the structural and functional properties of viral proteins, which are widely involved in regulatory and signaling processes. With chapters by leading research groups, it features current information on the structural and functional roles of intrinsic disorders in viral proteomes. It systematically addresses the measles, HIV, influenza, potato virus, forest virus, bovine virus, hepatitis, and rotavirus as well as viral genomics. After analyzing the unique features of each class of viral proteins, future directions for research and disease management are presented.
Author : Stuart G. Siddell
Publisher : Springer Science & Business Media
ISBN 13 : 1489915311
Total Pages : 424 pages
Book Rating : 4.4/5 (899 download)
Download or read book The Coronaviridae written by Stuart G. Siddell and published by Springer Science & Business Media. This book was released on 2013-06-29 with total page 424 pages. Available in PDF, EPUB and Kindle. Book excerpt: Coronaviruses were recognized as a group of enveloped, RNA viruses in 1968 and accepted by the International Committee on the Taxonomy of Viruses as a separate family, the Coronaviridae, in 1975. By 1978, it had become evident that the coronavirus genomic RNA was infectious (i. e. , positive strand), and by 1983, at least the framework of the coronavirus replication strategy had been per ceived. Subsequently, with the application of recombinant DNA techniques, there have been remarkable advances in our understanding of the molecular biology of coronaviruses, and a mass of structural data concerning coronavirus genomes, mRNAs, and pro teins now exists. More recently, attention has been focused on the role of essential and accessory gene products in the coronavirus replication cyde and a molecular analysis of the structure-function relation ships of coronavirus proteins. Nevertheless, there are still large gaps in our knowledge, for instance, in areas such as the genesis of coronavirus subgenomic mRNAs or the function of the coronavirus RNA-dependent RNA polymerase. The diseases caused by coronaviruses have been known for much longer than the agents themselves. Possibly the first coronavirus-related disease to be recorded was feline infectious peritonitis, as early as 1912. The diseases associ ated with infectious bronchitis virus, transmissible gastroenteritis virus, and murine hepatitis virus were all well known before 1950.
Author : Satya Prakash Gupta
Publisher : Academic Press
ISBN 13 : 0128096829
Total Pages : 518 pages
Book Rating : 4.1/5 (28 download)
Download or read book Viral Proteases and Their Inhibitors written by Satya Prakash Gupta and published by Academic Press. This book was released on 2017-07-03 with total page 518 pages. Available in PDF, EPUB and Kindle. Book excerpt: Viral Proteases and Their Inhibitors provides a thorough examination of viral proteases from their molecular components, to therapeutic applications. As information on three dimensional structures and biological functions of these viral proteases become known, unexpected protein folds and unique mechanisms of proteolysis are realized. This book investigates how this facilitates the design and development of potent antiviral agents used against life-threatening viruses. Users will find descriptions of each virus that detail the structure and function of viral proteases, discuss the design and development of inhibitors, and analyze the structure-activity relationships of inhibitors. This book is ideal biochemists, virologists and those working on antiviral agents. Provides comprehensive, state-of-the-art coverage of virus infections, the virus lifecycle, and mechanisms of protease inhibition Analyzes structure-activity relationships of inhibitors of each viral protease Presents an in-depth view of the structure and function of viral proteases
Author : Hamed Gouklani
Publisher :
ISBN 13 :
Total Pages : 362 pages
Book Rating : 4.:/5 (11 download)
Download or read book Functional Interactions of Structural and NS Proteins of Hepatitis C Virus written by Hamed Gouklani and published by . This book was released on 2011 with total page 362 pages. Available in PDF, EPUB and Kindle. Book excerpt: Hepatitis C virus (HCV) is a small enveloped virus with a positive-sense single stranded RNA genome. Based on its molecular genetic characteristics, the virus has been classified into the Hepacivirus genus of the family Flaviviridae. HCV is one of the major causes of chronic hepatitis which can lead to liver cirrhosis and hepatocellular carcinoma. According to the recent WHO published data, 123 million individuals are infected with HCV (approximately 3% of the world's population) throughout the world. Due to its highly variable nature, HCV is classified into six major genotypes. The HCV genome encodes a single polyprotein that is cleaved to yield at least 10 mature proteins (C, E1, E2, p7, NS2, NS3, NS4A, NS4B, NS5A and NS5B). The recently developed HCV cell culture system, based on the JFH1 strain of HCV, has provided an opportunity to study the role of the viral proteins in the complete HCV replication cycle in human hepatoma cells. How the viral proteins functionally interact during replication of HCV in cell culture is not completely understood. Passage of cell cultures transfected with HCV genomic RNA containing attenuating mutations allows for the selection of genomes with second site compensatory mutations that restore replication to wild type levels. Using this approach, the functional interactions of p7 and E2 with other viral proteins during HCV replication was investigated.A small protein of 63 amino acids, p7 is encoded at the junction of the structural and non-strucutural region. p7 is a highly hydrophobic, integral membrane protein and is classified in the viroporin family. In this thesis, it is shown that p7 is critical for production of viral particles and is implicated in a late step of particle assembly. Since the protein plays a critical role in the virus life cycle, chemical compounds that block p7 function are potential candidates for anti-viral therapy. In this thesis, a chimeric JFH1 genome that encodes the p7 protein of genotype (GT) 1b strain J4 was generated. The intergenotypic chimeric genome was nonviable in human hepatoma cells and infectious chimeric virions were only produced after cells harboring the chimeric genomes were passaged several times. To investigate the emergence of compensatory mutations in the viral proteins during cell passaging, the consensus sequences of the entire polyprotein coding regions of the wild type JFH1 and three chimeric viruses were determined. Sequence analysis revealed mutations in core, NS2, NS5A and NS5B. Reverse genetic analysis demonstrated that any one of the single mutations restored the infectivity of the defective chimeric genomes. These data suggest that there are critical genetic interactions between p7 with core, NS2, NS5A and NS5B. In addition, a stable physical interaction between p7 and NS2 is shown in a transient expression system. The HCV glycoproteins E1 and E2 are present on the surface of virions as a heterodimer that attach virions to host cell receptors and facilitate virus fusion and entry. HCV entry proceeds via attachment to glycosaminoglycans followed by binding to scavenger receptor type B class I, and the tetraspanin CD81. Recently, claudin-1 and occludin have emerged as additional receptors required for entry. E2 has a receptor binding domain (E2661RBD) that conatins three variable regions, hypervariable regions 1 (HVR1), HVR2 and the intergenotypic variable region (igVR). In this thesis, HVR1 of E2 was deleted in the context of full-length replication comptetent HCV. Deletion of HVR1 increases CD81-binding ability of the mutant and also increases its susceptibility to neutralizing antibody MAb 24. The infectivity of the HVR1 deleted virions was attenuated approximately 10-fold prior to accumulation of compensatory mutations. Sequencing of cDNA obtained from reverted virions revealed mutations in E1 (I262L) and E2 (N415D). Reverse genetic studies revealed that I262L improved the infectivity of HVR1 deleted virions 2.5 fold while N415D restored infectivity to wild type levels. These data suggest that mutations within E1 or E2 can compensate for the reduction in infectivity observed for HVR1 deleted viruses.In summary, this thesis demonstrates the importance of functional interactions between HCV proteins during virus morphogenesis and infectivity.
Author : Wang-Shick Ryu
Publisher : Academic Press
ISBN 13 : 0128009993
Total Pages : 441 pages
Book Rating : 4.1/5 (28 download)
Download or read book Molecular Virology of Human Pathogenic Viruses written by Wang-Shick Ryu and published by Academic Press. This book was released on 2016-03-30 with total page 441 pages. Available in PDF, EPUB and Kindle. Book excerpt: Molecular Virology of Human Pathogenic Viruses presents robust coverage of the key principles of molecular virology while emphasizing virus family structure and providing key context points for topical advances in the field. The book is organized in a logical manner to aid in student discoverability and comprehension and is based on the author’s more than 20 years of teaching experience. Each chapter will describe the viral life cycle covering the order of classification, virion and genome structure, viral proteins, life cycle, and the effect on host and an emphasis on virus-host interaction is conveyed throughout the text. Molecular Virology of Human Pathogenic Viruses provides essential information for students and professionals in virology, molecular biology, microbiology, infectious disease, and immunology and contains outstanding features such as study questions and recommended journal articles with perspectives at the end of each chapter to assist students with scientific inquiries and in reading primary literature. Presents viruses within their family structure Contains recommended journal articles with perspectives to put primary literature in context Includes integrated recommended reading references within each chapter Provides access to online ancillary package inclusive of annotated PowerPoint images, instructor’s manual, study guide, and test bank
Author : Irwin M. Arias
Publisher : John Wiley & Sons
ISBN 13 : 1119436826
Total Pages : 1156 pages
Book Rating : 4.1/5 (194 download)
Download or read book The Liver written by Irwin M. Arias and published by John Wiley & Sons. This book was released on 2020-03-09 with total page 1156 pages. Available in PDF, EPUB and Kindle. Book excerpt: Bridging the gap between basic scientific advances and the understanding of liver disease — the extensively revised new edition of the premier text in the field. The latest edition of The Liver: Biology and Pathobiology remains a definitive volume in the field of hepatology, relating advances in biomedical sciences and engineering to understanding of liver structure, function, and disease pathology and treatment. Contributions from leading researchers examine the cell biology of the liver, the pathobiology of liver disease, the liver’s growth, regeneration, metabolic functions, and more. Now in its sixth edition, this classic text has been exhaustively revised to reflect new discoveries in biology and their influence on diagnosing, managing, and preventing liver disease. Seventy new chapters — including substantial original sections on liver cancer and groundbreaking advances that will have significant impact on hepatology — provide comprehensive, fully up-to-date coverage of both the current state and future direction of hepatology. Topics include liver RNA structure and function, gene editing, single-cell and single-molecule genomic analyses, the molecular biology of hepatitis, drug interactions and engineered drug design, and liver disease mechanisms and therapies. Edited by globally-recognized experts in the field, this authoritative volume: Relates molecular physiology to understanding disease pathology and treatment Links the science and pathology of the liver to practical clinical applications Features 16 new “Horizons” chapters that explore new and emerging science and technology Includes plentiful full-color illustrations and figures The Liver: Biology and Pathobiology, Sixth Edition is an indispensable resource for practicing and trainee hepatologists, gastroenterologists, hepatobiliary and liver transplant surgeons, and researchers and scientists in areas including hepatology, cell and molecular biology, virology, and drug metabolism.
Author : Manoj C. Desai
Publisher : Royal Society of Chemistry
ISBN 13 : 1849737819
Total Pages : 551 pages
Book Rating : 4.8/5 (497 download)
Download or read book Successful Strategies for the Discovery of Antiviral Drugs written by Manoj C. Desai and published by Royal Society of Chemistry. This book was released on 2013-06-17 with total page 551 pages. Available in PDF, EPUB and Kindle. Book excerpt: The antiviral therapeutic area continues to rapidly generate meaningful new chemical entities; for example, for HIV alone more than 25 drugs have been approved, and in the next few years many individual drugs and single tablet regimens will be approved for the treatment of hepatitis C virus infection. The increasing success in the antiviral area could be due to targeting drugs at "non-self" genomes and to the patient population that is tolerant of manageable side effects and adaptable to inconvenient dosing. Aimed at medicinal chemists and emerging drug discovery scientists, the book is organized according to the various strategies deployed for the discovery and optimization of initial lead compounds. This book focuses on capturing tactical aspects of problem solving in antiviral drug design, an approach that holds special appeal for those engaged in antiviral drug development, but also appeals to the broader medicinal chemistry community based on its focus on tactical aspects of drug design.
Author : National Academies of Sciences, Engineering, and Medicine
Publisher : National Academies Press
ISBN 13 : 0309438020
Total Pages : 187 pages
Book Rating : 4.3/5 (94 download)
Download or read book Eliminating the Public Health Problem of Hepatitis B and C in the United States written by National Academies of Sciences, Engineering, and Medicine and published by National Academies Press. This book was released on 2016-06-01 with total page 187 pages. Available in PDF, EPUB and Kindle. Book excerpt: Hepatitis B and C cause most cases of hepatitis in the United States and the world. The two diseases account for about a million deaths a year and 78 percent of world's hepatocellular carcinoma and more than half of all fatal cirrhosis. In 2013 viral hepatitis, of which hepatitis B virus (HBV) and hepatitis C virus (HCV) are the most common types, surpassed HIV and AIDS to become the seventh leading cause of death worldwide. The world now has the tools to prevent hepatitis B and cure hepatitis C. Perfect vaccination could eradicate HBV, but it would take two generations at least. In the meantime, there is no cure for the millions of people already infected. Conversely, there is no vaccine for HCV, but new direct-acting antivirals can cure 95 percent of chronic infections, though these drugs are unlikely to reach all chronically-infected people anytime soon. This report, the first of two, examines the feasibility of hepatitis B and C elimination in the United States and identifies critical success factors. The phase two report will outline a strategy for meeting the elimination goals discussed in this report.
Author : Mei Hwei Chang
Publisher : Springer Science & Business Media
ISBN 13 : 3642389651
Total Pages : 293 pages
Book Rating : 4.6/5 (423 download)
Download or read book Viruses and Human Cancer written by Mei Hwei Chang and published by Springer Science & Business Media. This book was released on 2013-09-06 with total page 293 pages. Available in PDF, EPUB and Kindle. Book excerpt: Research on oncogenic viruses and related human cancers has advanced rapidly in the past decade. Most articles, however, focus on a specific oncogenic virus and cancer. There is consequently a need for a comprehensive, up-to-date monograph that offers broad and integrated knowledge. Viruses and Human Cancer – From Basic Science to Clinical Prevention is designed to meet this need by providing an advanced overview on the basic and clinical aspects of oncogenic viruses and the human cancers that they cause. Virology, virus-induced inflammation and tissue injuries, oncogenic mechanisms, epidemiology, and current and emerging preventive and therapeutic strategies are all discussed in detail. In addition, the book covers the individual aspects of seven oncogenic viruses, i.e., hepatitis B virus, hepatitis C virus, human papilloma virus, Epstein-Barr virus, human T-cell lymphotropic virus, Kaposi sarcoma-associated herpes virus, and Merkel cell polyomavirus, and the related human cancers.
Author : Michela Marongiu
Publisher :
ISBN 13 :
Total Pages : 246 pages
Book Rating : 4.:/5 (111 download)
Download or read book Studies on the hyperphosphorylation of hepatitis C virus non structural protein NS5A written by Michela Marongiu and published by . This book was released on 2009 with total page 246 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Author : Ralf Bartenschlager
Publisher : Springer Science & Business Media
ISBN 13 : 3642273408
Total Pages : 353 pages
Book Rating : 4.6/5 (422 download)
Download or read book Hepatitis C Virus: From Molecular Virology to Antiviral Therapy written by Ralf Bartenschlager and published by Springer Science & Business Media. This book was released on 2013-03-12 with total page 353 pages. Available in PDF, EPUB and Kindle. Book excerpt: Hepatitis C virus (HCV), a major causative agent of chronic liver disease, is spread throughout the world and around 170 million people are persistently infected. In this volume, world-leading experts in the field of HCV research have compiled the most recent scientific advances to provide a comprehensive and very timely overview of the various facets of HCV. The book starts with a discussion of the possible origin of HCV and its spread among the human population. The focus of the subsequent chapters is on available cell culture and in vivo models before shifting to the molecular and cellular principles underlying the viral replication cycle. These chapters are complemented by insightful descriptions of the innate and adaptive immune responses to HCV as well as the virus-associated pathogenesis. Finally, the development of antiviral therapies, which is closely linked with progress in basic research, and the implementation of those therapies into present and future daily clinical practice are highlighted.
Author : Susanne Modrow
Publisher : Springer
ISBN 13 : 9783642207174
Total Pages : 0 pages
Book Rating : 4.2/5 (71 download)
Download or read book Molecular Virology written by Susanne Modrow and published by Springer. This book was released on 2013-09-18 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: The book gives a comprehensive overview on the knowledge of virus infection relevant for humans and animals. For each virus family the molecular details of the virus particle and the viral replication cycle are described. In the case of virus types with relevance for human and/or animal health the data on molecular biology, genetics and virus-cell interaction are combined with those concerning, pathogenesis, epidemiology, clinics, prevention and therapy.
