Download or read book Influenza A Virus A Role for the RNA Polymerase in Viral Particle Assembly written by John F. Regan and published by . This book was released on 2005 with total page 660 pages. Available in PDF, EPUB and Kindle. Book excerpt: Influenza is an RNA virus whose segmented genome is encapsidated into viral ribonucleoprotein complexes (vRNPs). Upon infection, the vRNPs migrate into the nucleus where transcription and replication take place. The vRNPs contain a RNA-dependent RNA polymerase that is responsible for viral transcription and replication. The polymerase is composed of three subunits, PB1, PB2, and PA. PBI has polymerase activity and PB2 is involved in viral transcription. The function of PA is unclear. To help elucidate the role of PA in the viral life cycle, 16 conserved regions of PA were targeted for alanine substitution. A plasmid-based transfection system was used to generate recombinant influenza particles bearing each mutation, which were tested for viral viability and the ability of each mutant polymerase to transcribe and replicate a reporter. Mutations in the N-terminus were not well tolerated and resulted in either non-viable or attenuated viruses. One of the mutants, J10, was capable of RNA synthesis, yet did not create viral particles capable of plaque formation in MDCK cells. Specifically, when compared to wild-type, this mutant synthesized 50+/-7% vRNA, 86+/-12% mRNA, and 128+/-18% cRNA. These levels are compatible with viability, as mutants J8 (27%) and J12 (23%), produced significantly less vRNA than J10, yet were viable by plaque assay. The mRNAs generated from J10 polymerase were found to be translationally-active, and both the mutant protein and its RNA products were appropriately localized in the cytoplasm, where influenza assembly occurs. Nevertheless, J10 failed to generate infectious particles from cells in a plasmid-based influenza assembly assay, and hemagglutinating material from the supernatants of such cells contained little or no nuclease-resistant genomic RNA. These findings suggest that PA has a previously unrecognized role in assembly or release of influenza virions, perhaps influencing core structure or the packaging of vRNAs or other essential components into nascent influenza particles.
Download or read book Assembly of Enveloped RNA Viruses written by Monique Dubois-Dalcq and published by Springer Science & Business Media. This book was released on 2012-12-06 with total page 249 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book is a collection of critical reviews about a diverse group of virus families with two features in common: the stable repository of genetic information in each virus is RNA, and each virus modifies and appropriates a particular patch of the eukaryotic cell membrane system to complete its structure. The reviews take the reader from the level of virus genome structure and expression through the quaternary interactions between virus-specified elements and cellular components that cooperate to produce virus particles. There are spectacular illustrations in this volume, but it is much more than a picture gallery. Reading widely in this book can be an effective antidote to overspecialization: in these pages, you are likely to learn much about viruses and about cells that you didn't know before; you'll discover illuminating parallels between diverse virus families; you'll come away with a sharpened awareness of important things that are still to be learned. Memphis, Tenn. , Summer 1984 David W. Kingsbury Preface This book was written at the suggestion of Dr. David W. Kingsbury made at a work shop on viruses organized by the Multiple Sclerosis Society in Aspen, Colorado, U. S. A. , three years ago. Originally, we had thought to focus on the morphological aspects of viral assembly. Later, during our discussions on the process of budding of enveloped RNA viruses, it became evident that we should include biochemical data in our review and correlate them with the structural aspects of virus maturation.
Download or read book Virally Infected Cells written by J. Robin Harris and published by Springer Science & Business Media. This book was released on 1989-07-31 with total page 490 pages. Available in PDF, EPUB and Kindle. Book excerpt: Cellular virology has made tremendous advances in the past decade due to the availability and application of new immunological techniques together with the vast range of biochemical techniques and the continued impact of transmission electron microscopy. The chapters contained in this volume provide significant coverage of the subject of cellular virology as a whole. Considerable overall emphasis is placed upon the membrane biochemistry of viral proteins and glycoproteins within the infected cell. In the opening chapter Edouard Kurstak and his colleagues provide a useful survey on the detection of viral antigens and antibodies by immunoassays. This chapter, with its emphasis on the important role of immunology in present-day virology, sets the scene for the volume. Following this is an exciting presentation from Stefan Hoglund and his colleagues on ISCOMs and immunostimulation with viral antigens. This unique approach is already proving to be of value, particularly in animal virology. A somewhat pharmacological diversion appears in Chapter 3, by Kazukiyo Onodera and his colleagues, in which the biological activity of the damavaricin C derivatives is discussed. This chapter provides a link between the biochemical and the chemotherapeutic approach in cellular virology. Yet another specialist area is covered in Chapter 4 by Otto Schmidt and hnke Schuchmann-Feddersen, who discuss the role of virus-like particles in para site-host interactions of insects. Contributing a strong biomedical emphasis to the volume is the provocative chapter by Abraham Karpas on human leukemia and retroviruses.
Download or read book Viral Interactions with the Nucleus written by Erin Joanne Walker and published by Frontiers Media SA. This book was released on 2017-08-16 with total page 124 pages. Available in PDF, EPUB and Kindle. Book excerpt: Viruses cause numerous medically important diseases, affecting developing, developed, rich and poor alike. The diseases vary in severity, including chickenpox, smallpox, influenza, shingles, herpes, rabies, polio, Ebola, hanta fever, AIDS and the common cold, amongst others. Regardless of the type of tissue or organ affected, all viruses follow the same basic steps to infect host cells. Once in contact with host cells viruses release their genetic material into the cell followed by genome replication, production of viral proteins, assembly of the virus particle and egress from the infected cell. Viruses disrupt normal host cell processes in order to facilitate their own replication/assembly by re-directing cellular machinery for viral transcription, translation, assembly, release and by inhibiting antiviral responses. Regulated nuclear transport of macromolecules through the nuclear pore complex, the only means of transport across the nuclear membrane, is essential for normal cell function and an effective antiviral response. Many viruses disrupt or exploit the nucleocytoplasmic trafficking pathways in host cells. Cytoplasmic viruses exploit the host cell nucleocytoplasmic trafficking machinery to access nuclear functions and/or disrupt nuclear transport, while several DNA viruses use the trafficking pathways to enable export of their components into the cytoplasm; yet others complete their assembly within the nucleus and use nuclear export pathways to access the cytoplasm. Indeed, the many and varied interactions of viruses and viral proteins with nucleocytoplasmic trafficking components have been invaluable in pathway discovery. Importantly, mounting evidence suggests that these interactions play essential roles in virus replication/assembly and hence may be key to understanding pathophysiology of viral diseases. This Frontiers Research Topic is dedicated to the importance of nucleocytoplasmic trafficking to viral pathogenesis.
Download or read book Phosphorylation Controls Assembly and Activity of the Influenza Virus Replication Machinery written by Anthony Rohit Dawson and published by . This book was released on 2020 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Successful influenza virus replication requires that viral gene expression and genome replication are balanced during viral infection. Both of these tasks occur via the viral ribonucleoprotein (RNP) containing genomic RNA encapsidated by viral nucleoprotein (NP) and bound by the viral RNA-dependent RNA polymerase consisting of subunits PB1, PB2 and PA. RNP function is regulated by multiple host factors and post-translational modifications. In particular, studies presented here provide evidence that phosphorylation by host kinases controls the activities of all RNP proteins. The overall goal of this thesis is to define how host-mediated phosphorylation controls RNA synthesis of the influenza virus replication machinery. Initial studies sought to understand how RNP assembly is regulated. RNP assembly is required only for replication and assembly requires NP to oligomerizes along genomic RNA. We determined that phosphorylation of the oligomeric interface inhibits RNP assembly. These phosphorylation sites are conserved among influenza virus genera suggesting a common regulatory scheme. These studies also identified the host kinase PKC Îþ as a key modifier of NP and regulator of influenza virus RNA synthesis. Additional studies explored how phosphorylation controls the influenza virus polymerase. Each polymerase subunit possesses unique functions to enable transcription and genome replication. PB1 harbors the catalytic activity of the polymerase. We established that phosphorylation of PB1 controls both RNA binding and transcription by the viral polymerase. Moreover, prior studies determined that transcription by the polymerase occurs via a cap-snatching mechanism wherein the polymerase binds capped host mRNA, cleaves the 5' end to produce a short capped oligonucleotide, and uses the cleaved product to prime transcription of viral genes. The PB2 subunit harbors the required cap binding activity. We provide evidence that phosphorylation controls PB2 cap binding. The endonuclease activity required for cap snatching resides in PA. Experiments with PA phospho-mutants display severe defects in transcription, likely caused by impaired endonuclease activity. Some identified phosphorylated residues appear essential for total polymerase function, whereas the function of other phosphorylation events remains elusive. Thus, phosphorylation indirectly regulates genome replication through NP modifications and changes in RNP assembly, and directly regulates transcription and replication by modifying the polymerase. We also analyzed the phosphoproteome of synchronously influenza virus-infected cells. Viral phosphoproteins generally increase throughout infection commensurate with the abundance of these proteins, suggesting that viral protein phosphorylation does not change en masse to segregate functions of viral protein at discrete times during infection. In contrast, host phosphoprotein abundances show multiple patterns, potentially enabling key viral replication events. In sum, directed studies of specific phosphorylation events coupled with broad analysis of the host phosphoproteome during infection provide a larger framework to understand post translational control of the influenza virus replication cycle.
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.
Download or read book Conserved Polymerase Structural Features and Ubiquitination Regulate the Influenza Virus RNA Replication Machinery written by and published by . This book was released on 2016 with total page 158 pages. Available in PDF, EPUB and Kindle. Book excerpt: The influenza A virus polymerase is essential for the virus life cycle. The polymerase is a trimeric complex composed of subunits PA, PB1, and PB2 and associates with viral RNAs and nucleoprotein (NP) to form higher order ribonucleoprotein (RNP) complexes. In the context of these RNPs, the polymerase expresses viral genes and replicates the viral genome. The polymerase is also a major determinant of influenza virus host tropism and pathogenicity. It is a target for species-specific restriction of influenza viruses in mammals. Polymerases encoded by avian influenza viruses do not function efficiently in mammals. This restriction has been mapped to position 627 in the PB2 subunit, which is normally a glutamic acid in avian isolates. Conversely, a lysine is present at position 627 in most mammalian viral isolates and creates a basic face on the domain surface that confers high activity in mammals. In addition to species-specific regulation, the polymerase is also regulated temporally over the course of infection to ensure coordinated expression of viral genes as well as replication of the viral genome. Various host factors and processes have been implicated in regulation of the IAV polymerase function, including post-translational modifications, however the mechanisms are not fully understood. We created a series of mutants in the 627 domain of the PB2 subunit to alter the conserved “P[F/P]AAAPP” sequence motif and a number of conserved basic residues that give the domain surface a basic face. Mutating the basic face or the P[F/P]AAAP motif impaired polymerase activity, assembly of replication complexes and viral replication. We found that the P[F/P]AAAP motif residues were important for polymerase function in both human and chicken cells, suggesting that they play a structural role and are essential for overall polymerase function. We also identified PB2 positions 586 and 589 on the basic surface of the 627 domain to be species-specific determinants of polymerase function that are preferentially required for function in human versus avian cells. Thus, we identified new residues in the 627 domain that regulate overall polymerase function and those that function in a species-specific fashion. This work highlights the importance of the surface charge and structure of the PB2 627 domain for virus replication and host adaptation. We assessed the ubiquitination status of the RNP complex and investigated the effect of ubiquitin expression on polymerase function. We show that all protein subunits in the RNP complex are ubiquitinated and that their levels are not significantly affected, despite the well known activity of ubiquitin-mediated protein degradation. Instead, we found that ubiquitination and an active proteasome enhance polymerase activity. Ubiquitin expression up-regulates polymerase function causing increased accumulation of vRNA, cRNA and mRNA and enhanced viral gene expression during infection. We show that ubiquitin expression enhances polymerase activity independent of NP or RNP assembly. Ubiquitination and the proteasome pathway play multiple roles in the influenza virus cycle, and we now demonstrate that ubiquitination also modulates polymerase activity independent of protein degradation. Overall, we describe here key features of the influenza virus polymerase that regulate its function in a species-specific fashion and a new way in which a host cell process can be co-opted by the virus to enhance its polymerase function.
Download or read book Structure and Physics of Viruses written by Mauricio G. Mateu and published by Springer Science & Business Media. This book was released on 2013-06-04 with total page 734 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book contemplates the structure, dynamics and physics of virus particles: From the moment they come into existence by self-assembly from viral components produced in the infected cell, through their extracellular stage, until they recognise and infect a new host cell and cease to exist by losing their physical integrity to start a new infectious cycle. (Bio)physical techniques used to study the structure of virus particles and components, and some applications of structure-based studies of viruses are also contemplated. This book is aimed first at M.Sc. students, Ph.D. students and postdoctoral researchers with a university degree in biology, chemistry, physics or related scientific disciplines who share an interest or are actually working on viruses. We have aimed also at providing an updated account of many important concepts, techniques, studies and applications in structural and physical virology for established scientists working on viruses, irrespective of their physical, chemical or biological background and their field of expertise. We have not attempted to provide a collection of for-experts-only reviews focused mainly on the latest research in specific topics; we have not generally assumed that the reader knows all of the jargon and all but the most recent and advanced results in each topic dealt with in this book. In short, we have attempted to write a book basic enough to be useful to M.Sc and Ph.D. students, as well as advanced and current enough to be useful to senior scientists with an interest in Structural and/or Physical Virology.
Download or read book Essential Human Virology written by Jennifer Louten and published by Academic Press. This book was released on 2022-05-28 with total page 412 pages. Available in PDF, EPUB and Kindle. Book excerpt: Essential Human Virology, Second Edition focuses on the structure and classification of viruses, virus transmission and virus replication strategies based upon type of viral nucleic acid. Several chapters focus on notable and recognizable viruses and the diseases caused by them, including influenza, HIV, hepatitis viruses, poliovirus, herpesviruses and emerging and dangerous viruses. Additionally, how viruses cause disease (pathogenesis) is highlighted, along with discussions on immune response to viruses, vaccines, anti-viral drugs, gene therapy, the beneficial uses of viruses, research laboratory assays and viral diagnosis assays. Fully revised and updated with new chapters on coronaviruses, nonliving infectious agents, and notable non-human viruses, the book provides students with a solid foundation in virology. - Focuses on human diseases and the cellular pathology that viruses cause - Highlights current and cutting-edge technology and associated issues - Presents real case studies and current news highlights in each chapter - Features dynamic illustrations, chapter assessment questions, key terms, and a summary of concepts, as well as an instructor website with lecture slides, a test bank and recommended activities - Updated and revised, with new chapters on coronaviruses, nonliving infectious agents, and notable non-human viruses
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.
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
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.
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.
Download or read book Ribosome Structure and Protein Biosynthesis written by Aleksandr Sergeevich Spirin and published by Benjamin-Cummings Publishing Company. This book was released on 1986 with total page 440 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book RNA binding Proteins Regulate Influenza Virus Infection written by Mitchell Ledwith and published by . This book was released on 2022 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Viruses are obligate intracellular parasites that depend on host resources andmacromolecular machinery to selfishly replicate and spread genetic material. This genetic material can exist in multiple forms, with viruses utilizing RNA, DNA, and diverse combinations thereof to stably transmit between hosts. These diverse strategies require diverse replication schemes, e.g., DNA viruses must either encode or co-opt host DNA-dependent DNA polymerases to replicate a genome, and negative sense RNA viruses must encode and package RNA-dependent RNA polymerases in virons in order to replicate an RNA genome in the next host. Regardless of scheme, all viruses converge and are absolutely reliant on RNA, and more specifically the host ability to translate RNA molecules into proteins. Thus, both viruses and hosts have devoted significant coding capital in regulating RNA, with emphasis on the evolutionary struggle that exists at this nexus. The over-arching theme of this thesis is to illuminate how and why influenza viruses co- opt, manipulate, and embrace RNA regulation strategies of human hosts. In the first chapter of this thesis, we profiled the RNA-binding characteristics of IFIT2, a canonically anti-viral and interferon-induced host protein, which influenza virus utilizes in a pro- viral manner. Through genome-wide cross-linking immunopreciptation sequencing (CLIP-seq) experiments, we found that IFIT2 binds mRNAs including those of influenza virus. We validated IFIT2 as an mRNA-binding protein, and found that IFIT2 specifically binds AU-rich regions in human RNAs with a preference for binding the mRNAs of other interferon-induced proteins. To accomplish a broadly anti-viral and selectively pro-viral function, we found that IFIT2 binds mRNAs to enhance their translation. Polysome and ribosome-profiling revealed that IFIT2-bound RNAs are poorly translated in the absence of IFIT2, including influenza virus mRNAs. This links the RNA-binding ability of IFIT2 to a functional role in translation, potentially explaining thexi contradiction between the previously observed anti-viral phenotypic role for IFIT2 and the mechanistically observed pro-viral role for IFIT2 in the context of influenza virus. Altogether, these data describe a new node for the regulation of translation during interferon responses and highlight the regulatory volatility that exists at the mRNA interface during infection. In the second chapter of this thesis, we sought to understand the non-specific RNA-binding capability of the influenza virus nucleoprotein, which binds and protects the negative-sense RNA genome to facilitate gene expression and genome replication. Despite this well-established role, the incongruity of the specificity of NP for the viral genome and known biochemical promiscuity of NP is not reconciled. To address this, we perfomed cross-linking immunoprecipitation sequencing to unbiasedly determine the identity of NP-bound RNAs during infection. NP binds the viral genome and anti-genome, but also engages with a number of discrete classes of host small non-coding RNAs. Many of these RNAs have been shown to be host-derived RIG-I agonists during DNA virus infections, or structurally resemble validated RIG-I agonists. We profiled the RNAs bound by RIG-I during infection with quantitative CLIP-seq and found that host RNAs are bound and sampled by RIG-I, and NP likely interferes with the ability of RIG-I to sample endogenous and exogenous agonists. These data show that NP not only acts as a structural component of the influenza gene expression and replication machinery, but also acts as a viral countermeasure for innate sensing of immunogenic RNAs. As a whole, this thesis describes two dissimilar instances by which influenza manipulates host RNA regulation. While the context of these host protein:viral mRNA and viral protein:host non-coding RNA interactions are different, they collectively suggest that RNA regulation during the host innate response to viral infection is an essential and commonplace strategy, but often leaves the host exposed to quickly adapting viral pathogens.
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.
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 443 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.
