Discovery and Characterization of Influenza Virus RNA Secondary Structures

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ISBN 13 :
Total Pages : 156 pages
Book Rating : 4.:/5 (844 download)

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Book Synopsis Discovery and Characterization of Influenza Virus RNA Secondary Structures by : Salvatore F. Priore

Download or read book Discovery and Characterization of Influenza Virus RNA Secondary Structures written by Salvatore F. Priore and published by . This book was released on 2013 with total page 156 pages. Available in PDF, EPUB and Kindle. Book excerpt: "PART I: Influenza virus is a significant public health threat, partially because of its capacity to readily exchange gene segments between different host species to form novel pandemic strains. Even though influenza virus uses RNA exclusively throughout its entire life cycle, little is known about the structure of the Influenza A genome and transcriptome. This works presents bioinformatics efforts to discover and characterize RNA secondary structures in both the (+) and ( - )RNA orientations of influenza A virus. All available unique influenza A sequences from the NCBI database were used to identify 20 likely structured regions, primarily in the (+)RNA. One of these predictions is verified and refined using small molecule mapping and isoenergetic microarrays for a conserved region of the Segment 8 (NS1/NEP) intron. Part II: In addition to locally conserved structure, this work examines the global RNA secondary structure in coding regions of both Influenza A and B. For Influenza A, segments 1, 5, 7 and 8 show evidence of wide-spread structure conservation. This phenomenon is referred to as Global Ordered RNA Structure, or GORS. On average the predicted thermodynamic stability of each coding region segregated based on the host species with avian having the most stable folding free energies followed by swine and then human. Similarly, a study of Influenza B virus, which infects primarily humans, showed GORS in Segments 1, 2, 5 and 8. In silico codon mutations that maintained the amino acid sequence for each segment demonstrate the relatively unstable folding free energies of influenza B coding regions. Together these results highlight some of the molecular similarities and differences between influenza A and B and demonstrate the evolutionary adaptation of Influenza"--Page ix.

RNA Secondary Structure Discovery and Characterization

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ISBN 13 :
Total Pages : 460 pages
Book Rating : 4.:/5 (779 download)

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Book Synopsis RNA Secondary Structure Discovery and Characterization by : Walter Nicholaos Panagiotis Moss

Download or read book RNA Secondary Structure Discovery and Characterization written by Walter Nicholaos Panagiotis Moss and published by . This book was released on 2011 with total page 460 pages. Available in PDF, EPUB and Kindle. Book excerpt: "Part I. Analysis of the R2 retrotransposons from multiple silkmoth and fruit fly species have revealed three segments that contain conserved RNA secondary structures. These conserved structures play important roles in the propagation of the R2 element, including R2 RNA processing and transposon integration into the host genome as well as a likely role in translation. Two of the structured regions comprise protein binding sites: one is located in the 3' untranslated region (UTR) and the other is in the 5' UTR close to the putative start of the R2 open reading frame (ORF). The 5' structure was determined using a combination of chemical mapping, oligonucleotide binding, NMR and sequence analysis and contains an unusual pseudoknot structure. A review of the three conserved structures is presented. The third structure occurs at the 5' end of the R2 RNA and is responsible for self-cleavage of the 5' end of the element from a 28S ribosomal RNA co-transcript. Part II. Influenza A is a negative sense RNA virus of significant public health concern. While much is understood about the life cycle of the virus, knowledge of RNA secondary structure in influenza A virus is sparse. Predictions of RNA secondary structure can focus experimental efforts. The present study analyzes coding regions of the eight viral genome segments in both the (+) and ( - ) sense RNA for conserved secondary structure. The predictions are based on identifying regions of unusual thermodynamic stabilities and are correlated with studies of suppression of synonymous codon usage (SSCU). The results indicate that secondary structure is favored in the (+) sense influenza RNA. Twenty regions with putative conserved RNA structure have been identified, including two previously described structured regions. Of these predictions, eight have high thermodynamic stability and SSCU, with five of these corresponding to current annotations (e.g., splice sites). The remaining 12 are predicted by the thermodynamics alone. Secondary structures with high conservation of base-pairing are proposed within the five regions having known function. A combination of thermodynamics, amino acid and nucleotide sequence comparisons along with SSCU was essential for revealing potential secondary structures"--Leaves viii-ix.

Viral RNA Secondary Structures

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ISBN 13 :
Total Pages : pages
Book Rating : 4.:/5 (14 download)

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Book Synopsis Viral RNA Secondary Structures by : Rachel J. Hagey

Download or read book Viral RNA Secondary Structures written by Rachel J. Hagey and published by . This book was released on 2018 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: RNA viruses cause a variety of acute and chronic diseases in humans. In addition to encoding for viral proteins, the genomes of RNA viruses often harbor secondary and tertiary RNA structures that have been associated with functions essential for successful virus replication and propagation. While antiviral research has focused almost exclusively on targeting viral proteins, the importance of RNA structural elements in virus lifecycles suggest these motifs could be promising therapeutic targets. In this thesis, I will dissect the contributions and druggability of RNA structures and complexes in two distinct phases of the viral lifecycle: first, in the virus packaging and production of influenza A virus (IAV), a negative-strand segmented RNA virus responsible for severe, sometimes fatal respiratory disease with pandemic potential; and second, in the replication complex of hepatitis C virus (HCV), a positive-strand RNA virus associated with chronic liver disease and cancer. To characterize the role of RNA secondary structures in IAV virus packaging, I employed the chemical mapping technique, Selective 2′ Hydroxyl Acylation analyzed by Primer Extension (SHAPE), which uses experimental probing data to guide computational modeling of high resolution RNA structure. This method enabled me to determine the RNA secondary structure of the IAV 5′ packaging signal region of virus genome segment PB2, the structures of known mutations in PB2 that disrupt virus packaging, as well as the discovery and characterization of novel mutants. Cutting-edge multidimensional mapping methods, Mutate-and-Map and Mutate-Map-Rescue, built upon this technical base and provided structural validation through discovery of compensatory mutant partners, which later informed both the in vivo exploration of packaging-defective viruses, as well as the design of locked nucleic acids (LNAs) targeting this structure. In vitro and in vivo drug targeting by LNAs of this IAV packaging signal structure exhibited powerful prophylactic and therapeutic efficacy. Combined, this work points to the promise of RNA secondary structures as valid antiviral targets, and sheds new light on IAV genome packaging mechanisms. The second section of my thesis built upon previous research in the lab. SHAPE was again employed to map both the RNA secondary structure of the HCV 5′ internal ribosomal entry site (IRES) and the structural interaction between the virus's 5′ untranslated region (UTR) and the miR-122 complex found to mediate viral replication. As an extension of this investigation, we sought to better parse the interaction of the viral replication complex with the host membrane in real-time. To do so, we employed a supported lipid-bilayer (SLB) platform and coupled it with quartz crystal microbalance with dissipation (QCM-D) to reconstitute and explore how components of the HCV replicase complex affect viral RNA replication and in vitro RNA transcription. The core enzyme of this complex, the NS5B RNA-dependent RNA polymerase, is required for in vivo virus replication and is a prime drug target for current and future HCV antiviral therapies. The reconstitution of full length NS5B in a membranous environment capable of active polymerase function, however, had not been demonstrated. Here, the SLB/QCM-D platform made it possible to reconstruct an in silico biological mimic of the host membrane to quantitatively probe and observe interactions between the membrane, the HCV viral RNA template and its associated viral proteins in real time. Together, these provide strong proof-of-concept for use of this technique in further understanding of the molecular details of HCV genome replication and future drug screening applications.

RNA Structure and Function of Influenza Virus

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ISBN 13 :
Total Pages : 138 pages
Book Rating : 4.:/5 (11 download)

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Book Synopsis RNA Structure and Function of Influenza Virus by : Tian Jiang

Download or read book RNA Structure and Function of Influenza Virus written by Tian Jiang and published by . This book was released on 2015 with total page 138 pages. Available in PDF, EPUB and Kindle. Book excerpt: "Influenza viruses are negative-sense RNA viruses, which are a significant public health threat. Among the three different species of influenza, influenza A virus poses the biggest health risk. Currently, few drugs treat influenza; neuraminidase inhibitors are essentially the only therapeutics available. Moreover, sporadic cases of drug-resistant influenza viruses have been detected worldwide. The once widely used adamantanes are now mostly ineffective towards currently circulating influenza (H3N2). Thus, it is important to develop novel antiviral treatments as well as more effective vaccines. RNA structure plays key roles in the replication, transcription and translation of many viruses including influenza. However, little is known about influenza RNA structure. Recently, bioinformatics analysis predicted conserved and stable secondary structure in segments 7 and 8 of influenza A, which are alternatively spliced. Part I: A region 79 nucleotides downstream from the 5' splice site in segment 7 was predicted to have an especially stable and conserved secondary structure, using a combination of thermodynamic stability and comparative sequence analysis. This sequence and predicted structure are conserved within influenza A viruses that infect human, swine, and avian species. A multi-branch model was predicted for the consensus sequence of all wild type sequences available in the National Center for Biotechnology Information influenza virus resource. A possible alternative hairpin structure was also hypothesized for this region, with equally conserved base pairing and similar predicted free energy. In this work, a combination of mutagenesis, nondenaturing polyacrylamide gel electrophoresis, enzymatic/chemical mapping, isoenergetic microarray mapping, and NMR indicated that only the multi-branch structure forms in solution. Potential tertiary interactions in the structure were also identified. Part II: The biological function of the conserved structures in influenza A virus segments 7 and 8 were evaluated. A recombinant influenza H1N1 pandemic-causing strain containing mutations in structured regions were generated. Conserved RNA base pairs or loops in segments 7 and 8 were mutated to affect specific regions of secondary structure. In four cases, 2-nt mutations were made as designed with an ensemble defect program to completely change the predicted secondary structure. Virus growth kinetics of the wild type and mutant viruses were measured in vitro in tissue culture and in vivo in mice. qRT-PCR was used to measure the change in mRNA isoforms compared to the wild-type virus. The results show that disrupting conserved RNA structure may inhibit splicing of mRNA and/or attenuate viral replication. These motifs can serve as new targets for designing novel vaccines and therapeutics against influenza. In addition, it is proof of concept that therapeutic targets can be defined through genomic sequence analysis."--Pages vii-viii.

The Threat of Pandemic Influenza

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Publisher : National Academies Press
ISBN 13 : 0309095042
Total Pages : 431 pages
Book Rating : 4.3/5 (9 download)

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Book Synopsis The Threat of Pandemic Influenza by : Institute of Medicine

Download or read book The Threat of Pandemic Influenza written by Institute of Medicine and published by National Academies Press. This book was released on 2005-04-09 with total page 431 pages. Available in PDF, EPUB and Kindle. Book excerpt: Public health officials and organizations around the world remain on high alert because of increasing concerns about the prospect of an influenza pandemic, which many experts believe to be inevitable. Moreover, recent problems with the availability and strain-specificity of vaccine for annual flu epidemics in some countries and the rise of pandemic strains of avian flu in disparate geographic regions have alarmed experts about the world's ability to prevent or contain a human pandemic. The workshop summary, The Threat of Pandemic Influenza: Are We Ready? addresses these urgent concerns. The report describes what steps the United States and other countries have taken thus far to prepare for the next outbreak of "killer flu." It also looks at gaps in readiness, including hospitals' inability to absorb a surge of patients and many nations' incapacity to monitor and detect flu outbreaks. The report points to the need for international agreements to share flu vaccine and antiviral stockpiles to ensure that the 88 percent of nations that cannot manufacture or stockpile these products have access to them. It chronicles the toll of the H5N1 strain of avian flu currently circulating among poultry in many parts of Asia, which now accounts for the culling of millions of birds and the death of at least 50 persons. And it compares the costs of preparations with the costs of illness and death that could arise during an outbreak.

The Pathology of Influenza

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ISBN 13 :
Total Pages : 164 pages
Book Rating : 4.A/5 ( download)

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Book Synopsis The Pathology of Influenza by : Milton C. Winternitz

Download or read book The Pathology of Influenza written by Milton C. Winternitz and published by . This book was released on 1920 with total page 164 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Flu

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Publisher : Farrar, Straus and Giroux
ISBN 13 : 1429979356
Total Pages : 378 pages
Book Rating : 4.4/5 (299 download)

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Book Synopsis Flu by : Gina Kolata

Download or read book Flu written by Gina Kolata and published by Farrar, Straus and Giroux. This book was released on 2011-04-01 with total page 378 pages. Available in PDF, EPUB and Kindle. Book excerpt: Veteran journalist Gina Kolata's Flu: The Story of the Great Influenza Pandemic of 1918 and the Search for the Virus That Caused It presents a fascinating look at true story of the world's deadliest disease. In 1918, the Great Flu Epidemic felled the young and healthy virtually overnight. An estimated forty million people died as the epidemic raged. Children were left orphaned and families were devastated. As many American soldiers were killed by the 1918 flu as were killed in battle during World War I. And no area of the globe was safe. Eskimos living in remote outposts in the frozen tundra were sickened and killed by the flu in such numbers that entire villages were wiped out. Scientists have recently rediscovered shards of the flu virus frozen in Alaska and preserved in scraps of tissue in a government warehouse. Gina Kolata, an acclaimed reporter for The New York Times, unravels the mystery of this lethal virus with the high drama of a great adventure story. Delving into the history of the flu and previous epidemics, detailing the science and the latest understanding of this mortal disease, Kolata addresses the prospects for a great epidemic recurring, and, most important, what can be done to prevent it.

Influenza Virus Sialidase - A Drug Discovery Target

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Publisher : Springer Science & Business Media
ISBN 13 : 3764389273
Total Pages : 184 pages
Book Rating : 4.7/5 (643 download)

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Book Synopsis Influenza Virus Sialidase - A Drug Discovery Target by : Mark Itzstein

Download or read book Influenza Virus Sialidase - A Drug Discovery Target written by Mark Itzstein and published by Springer Science & Business Media. This book was released on 2011-09-01 with total page 184 pages. Available in PDF, EPUB and Kindle. Book excerpt: Influenza continues to be an ongoing problem despite the existence of vaccines and drugs. Disease outbreaks can occur relatively quickly as witnessed with the recent emergence of the influenza virus A/H1N1 pandemic. The development of new anti-influenza drugs is thus a major challenge. This volume describes all aspects of the virus structure and function relevant to infection. The focus is on drug discovery of inhibitors to the enzyme sialidase, which plays a key role in the infectious lifecycle of the virus. Following an overview of the influenza virus, the haemagglutinin, the interactions with the cell receptors and the enzymology of virus sialidase, recent results in drug design are presented. These include a full coverage of the design, synthesis and evaluation of carbohydrate as well as non-carbohydrate influenza virus sialidase inhibitors. Further reviews of the clinical experience with influenza virus sialidase inhibitors and of the development of resistance to these inhibitor drugs complement the topic.

Coronaviruses

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Publisher : Humana
ISBN 13 : 9781071609026
Total Pages : 278 pages
Book Rating : 4.6/5 (9 download)

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Book Synopsis Coronaviruses by : Helena J. Maier

Download or read book Coronaviruses written by Helena J. Maier and published by Humana. This book was released on 2021-09-08 with total page 278 pages. Available in PDF, EPUB and Kindle. Book excerpt: This detailed new edition provides a comprehensive collection of protocols applicable to all members of the Coronavirinae sub-family currently and that are also transferrable to other fields of virology. Beginning with a section on detection, discovery, and evolution, the volume continues with coverage of propagation and titration of coronaviruses, genome manipulation, study of virus-host interactions, as well as imaging coronavirus infections. Written for the highly successful Methods in Molecular Biology series, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and cutting-edge, Coronaviruses: Methods and Protocols, Second Edition serves as a valuable guide to researchers working to identify and control viruses with increased potential to cross the species barrier and to develop the diagnostics, vaccines, and antiviral therapeutics that are required to manage future outbreaks in both humans and animals.

Molecular Virology

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Publisher : Springer
ISBN 13 : 9783642207174
Total Pages : 0 pages
Book Rating : 4.2/5 (71 download)

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Book Synopsis Molecular Virology by : Susanne Modrow

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.

Influenza Virology

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Publisher : Horizon Scientific Press
ISBN 13 : 9781904455066
Total Pages : 367 pages
Book Rating : 4.4/5 (55 download)

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Book Synopsis Influenza Virology by : Yoshihiro Kawaoka

Download or read book Influenza Virology written by Yoshihiro Kawaoka and published by Horizon Scientific Press. This book was released on 2006 with total page 367 pages. Available in PDF, EPUB and Kindle. Book excerpt: World renowned scientists critically review the most important issues in this rapidly expanding field.

SARS, MERS and other Viral Lung Infections

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Publisher : European Respiratory Society
ISBN 13 : 1849840709
Total Pages : 148 pages
Book Rating : 4.8/5 (498 download)

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Book Synopsis SARS, MERS and other Viral Lung Infections by : David S. Hui

Download or read book SARS, MERS and other Viral Lung Infections written by David S. Hui and published by European Respiratory Society. This book was released on 2016-06-01 with total page 148 pages. Available in PDF, EPUB and Kindle. Book excerpt: Viral respiratory tract infections are important and common causes of morbidity and mortality worldwide. In the past two decades, several novel viral respiratory infections have emerged with epidemic potential that threaten global health security. This Monograph aims to provide an up-to-date and comprehensive overview of severe acute respiratory syndrome, Middle East respiratory syndrome and other viral respiratory infections, including seasonal influenza, avian influenza, respiratory syncytial virus and human rhinovirus, through six chapters written by authoritative experts from around the globe.

Virus Protein and Nucleoprotein Complexes

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Publisher : Springer
ISBN 13 : 9811084564
Total Pages : 442 pages
Book Rating : 4.8/5 (11 download)

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Book Synopsis Virus Protein and Nucleoprotein Complexes by : J. Robin Harris

Download or read book Virus Protein and Nucleoprotein Complexes written by J. Robin Harris and published by Springer. This book was released on 2018-06-13 with total page 442 pages. Available in PDF, EPUB and Kindle. Book excerpt: The Subcellular Biochemistry series has recently embarked upon an almost encyclopaedic coverage of topics relating to the structure and function of macromolecular complexes (Volumes 82, 83 and 87). The present multi-author text covers numerous aspects of current research into molecular virology, with emphasis upon viral protein and nucleoprotein structure and function. Structural data from cryo-electron microscopy and X-ray crystallography is displayed throughout the book. The 17 chapters in the book cover diverse interesting topics, all currently under investigation, contributed by authors who are active actively involved in present-day research. Whilst structural aspects predominate, there is much consideration of the structure-function relationship. In addition, the book correlates with and extends from Volume 68 of the series “Structure and Physics of Viruses: An Integrated Textbook”. This book is directed primarily at professionals that work in the broad field of Structural Biology and will be of particular interest to Structural Virologists. The editors, David Bhella and Robin Harris, have much experience in virology and protein structure, respectively. Dr Bhella is Director of the Scottish Macromolecular Imaging Centre. Professor Robin Harris is the long-standing Series Editor of the Subcellular Biochemistry series. He has edited and contributed to several books in the series.

Viral Molecular Machines

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Publisher : Springer Science & Business Media
ISBN 13 : 1461409802
Total Pages : 685 pages
Book Rating : 4.4/5 (614 download)

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Book Synopsis Viral Molecular Machines by : Michael G. Rossmann

Download or read book Viral Molecular Machines written by Michael G. Rossmann and published by Springer Science & Business Media. This book was released on 2012-02-02 with total page 685 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book will contain a series of solicited chapters that concern with the molecular machines required by viruses to perform various essential functions of virus life cycle. The first three chapters (Introduction, Molecular Machines and Virus Architecture) introduce the reader to the best known molecular machines and to the structure of viruses. The remainder of the book will examine in detail various stages of the viral life cycle. Beginning with the viral entry into a host cell, the book takes the reader through replication of the genome, synthesis and assembly of viral structural components, genome packaging and maturation into an infectious virion. Each chapter will describe the components of the respective machine in molecular or atomic detail, genetic and biochemical analyses, and mechanism. Topics are carefully selected so that the reader is exposed to systems where there is a substantial infusion of new knowledge in recent years, which greatly elevated the fundamental mechanistic understanding of the respective molecular machine. The authors will be encouraged to simplify the detailed knowledge to basic concepts, include provocative new ideas, as well as design colorful graphics, thus making the cutting-edge information accessible to broad audience.

Advances in Planar Lipid Bilayers and Liposomes

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Publisher : Academic Press
ISBN 13 : 0123965349
Total Pages : 358 pages
Book Rating : 4.1/5 (239 download)

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Book Synopsis Advances in Planar Lipid Bilayers and Liposomes by : Ales Iglic

Download or read book Advances in Planar Lipid Bilayers and Liposomes written by Ales Iglic and published by Academic Press. This book was released on 2012-09-04 with total page 358 pages. Available in PDF, EPUB and Kindle. Book excerpt: Advances in Planar Lipid Bilayers and Liposomes volumes cover a broad range of topics, including main arrangements of the reconstituted system, namely planar lipid bilayers as well as spherical liposomes. The invited authors present the latest results of their own research groups in this exciting multidisciplinary field. Incorporates contributions from newcomers and established and experienced researchers Explores the planar lipid bilayer systems and spherical liposomes from both theoretical and experimental perspectives Serves as an indispensable source of information for new scientists

Recoding: Expansion of Decoding Rules Enriches Gene Expression

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Publisher : Springer Science & Business Media
ISBN 13 : 0387893822
Total Pages : 473 pages
Book Rating : 4.3/5 (878 download)

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Book Synopsis Recoding: Expansion of Decoding Rules Enriches Gene Expression by : John F. Atkins

Download or read book Recoding: Expansion of Decoding Rules Enriches Gene Expression written by John F. Atkins and published by Springer Science & Business Media. This book was released on 2010-03-10 with total page 473 pages. Available in PDF, EPUB and Kindle. Book excerpt: The literature on recoding is scattered, so this superb book ?lls a need by prov- ing up-to-date, comprehensive, authoritative reviews of the many kinds of recoding phenomena. Between 1961 and 1966 my colleagues and I deciphered the genetic code in Escherichia coli and showed that the genetic code is the same in E. coli, Xenopus laevis, and guinea pig tissues. These results showed that the code has been c- served during evolution and strongly suggested that the code appeared very early during biological evolution, that all forms of life on earth descended from a c- mon ancestor, and thus that all forms of life on this planet are related to one another. The problem of biological time was solved by encoding information in DNA and retrieving the information for each new generation, for it is easier to make a new organism than it is to repair an aging, malfunctioning one. Subsequently, small modi?cations of the standard genetic code were found in certain organisms and in mitochondria. Mitochondrial DNA only encodes about 10–13 proteins, so some modi?cations of the genetic code are tolerated that pr- ably would be lethal if applied to the thousands of kinds of proteins encoded by genomic DNA.

Virus Structure

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Publisher : Elsevier
ISBN 13 : 0080493777
Total Pages : 610 pages
Book Rating : 4.0/5 (84 download)

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Book Synopsis Virus Structure by :

Download or read book Virus Structure written by and published by Elsevier. This book was released on 2003-10-02 with total page 610 pages. Available in PDF, EPUB and Kindle. Book excerpt: Virus Structure covers the full spectrum of modern structural virology. Its goal is to describe the means for defining moderate to high resolution structures and the basic principles that have emerged from these studies. Among the topics covered are Hybrid Vigor, Structural Folds of Viral Proteins, Virus Particle Dynamics, Viral Gemone Organization, Enveloped Viruses and Large Viruses. Covers viral assembly using heterologous expression systems and cell extracts Discusses molecular mechanisms in bacteriophage T7 procapsid assembly, maturation and DNA containment Includes information on structural studies on antibody/virus complexes