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 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 Textbook of Influenza written by Robert G. Webster and published by John Wiley & Sons. This book was released on 2014-01-06 with total page 684 pages. Available in PDF, EPUB and Kindle. Book excerpt: The Textbook of Influenza is a comprehensive resource covering all aspects of influenza, from the genetic and molecular biology of the virus through to clinical aspects of the disease and the latest drug developments and treatments. This new edition has been completely revised and reflects the integration of disciplines concerning the emergence, evolution, pathogenesis and control of influenza viruses in the field of human and veterinary public health. Textbook of Influenza examines the lessons learnt from the latest pandemic and provides the current state of knowledge for many yet unresolved issues related to virus origin, spread, pathogenesis and disease severity to better prepare for future pandemics. It covers the background to recent advances in influenza genomics and reverse genetics which have allowed the identification of virus virulence factors and the analysis and reconstruction of influenza viruses such as the 1918 Spanish flu strain. This new edition is divided into eight key sections, containing chapters co-written by international experts from both the clinical and scientific communities, covering: • Influenza Perspectives • Structure and Replication • Evolution and Ecology • Epidemiology and Surveillance • Immunology • Vaccines and Vaccine Development • Clinical Aspects and Antivirals • Public Health Textbook of Influenza is for all those working in the area of influenza including clinical and basic scientists, immunologists, molecular and structural virologists, public health officials and global pandemic control planners.

Download or read book The Fate of RNA and RNA Binding Proteins in Sindbis Virus Infection written by Shuai Ni and published by . This book was released on 2020 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:

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.

Download or read book The Eukaryotic Ribosome written by Heinz Bielka and published by Walter de Gruyter GmbH & Co KG. This book was released on 1982-12-31 with total page 340 pages. Available in PDF, EPUB and Kindle. Book excerpt: No detailed description available for "The Eukaryotic Ribosome".

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.

Download or read book Virus Bioinformatics written by Manja Marz and published by MDPI. This book was released on 2020-02-21 with total page 330 pages. Available in PDF, EPUB and Kindle. Book excerpt: Virus bioinformatics is evolving and succeeding as an area of research in its own right, representing the interface of virology and computer science. Bioinformatic approaches to investigate viral infections and outbreaks have become central to virology research, and have been successfully used to detect, control, and treat infections of humans and animals. As part of the Third Annual Meeting of the European Virus Bioinformatics Center (EVBC), we have published this Special Issue on Virus Bioinformatics.

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 248 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 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 RNA Tagging written by Manfred Heinlein and published by Humana. This book was released on 2021-08-08 with total page 490 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book provides a compendium of state-of-the-art methods for the labeling, detection, and purification of RNA and RNA-protein complexes and thereby constitutes an important toolbox for researchers interested in understanding the complex roles of RNA molecules in development, signaling, and disease. Beginning with a section on in situ detection of RNA molecules using FISH techniques, the volume continues with parts exploring in vivo imaging of RNA transport and localization, imaging and analysis of RNA uptake and transport between cells, identification and analysis of RNA-binding proteins, guide RNAs in genome editing, as well as other specific analytical techniques. 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 practical, RNA Tagging: Methods and Protocols serves as a vital reference for researchers looking to further the increasingly important research in RNA biology.

Download or read book Host RNA Degradation Pathways and Influenza A Virus Interplay written by Marion Declercq and published by . This book was released on 2019 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: RNA decay is a central cellular process as it regulates RNA stability and quality and thereby gene expression, which is essential to ensure proper cellular physiology and establishment of adapted responses to viral infection. Global takeover of gene expression machineries and rewiring of the cellular environment is key to the success of viral infection. Cellular proteome and viral replication are tightly connected and cellular RNA processing, stability, quality and decay accordingly influence the fate of the viral cycle. Growing evidence points towards the existence of a large interplay between eukaryotic RNA turnover machineries and viral proteins. Viruses not only evolved mechanisms to evade those RNA degradation pathways, but they also manipulate them to promote viral replication.Influenza A viruses (IAV) are major pathogens responsible for yearly epidemics and occasional pandemics. To complete their viral cycle, IAVs rely on many cellular proteins and establish a complex and highly coordinated interplay with the host proteome. Growing evidence supports the existence of a complex interplay between IAV viral proteins and RNA decay machineries. Unraveling such interplay is therefore essential to gain a better understanding of the IAV life cycle, required for the development of antiviral strategies. This led us to systematically screen interactions between viral proteins involved in IAV replication and a selected set of 75 cellular proteins carrying exoribonucleases activities or associated with RNA decay machineries. A total of 18 proteins were identified as interactors of at least one viral protein tested. Analysis of the interaction network highlighted a specific and preferential targeting of RNA degradation pathways by IAV proteins. Among validated interactors, a targeted RNAi screen identified nine factors as required for viral multiplication. We chose to focus on the 3'-5' exoribonuclease 1 (ERI1), found in our screen as an interactor of several components of the vRNPs (viral RiboNucleoProtein) (PB2, PB1 and NP). The ERI1 protein is a major player in the control of cellular gene expression as it is essential for the maturation and decay of histone mRNA, maturation of 5.8S rRNA and miRNA homeostasis in mammalian cells. Exploring the interplay between ERI1 and viral proteins during the course of IAV infection we found that i) ERI1 promotes viral transcription, and both of its activities - RNA binding and exonuclease - are required, ii) ERI1 interacts with viral proteins in an RNA dependent manner, iii) ERI1 interacts with the transcribing vRNPs, iv) viral proteins interact with a form of ERI1 that is associated to histone mRNA. Ultimately, our data point to a model where ERI1 associated to histone mRNA is co-opted by the transcribing viral polymerase, thereby promoting IAV multiplication, through a mechanism that remains to be precisely determined. Targeting of ERI1 by IAV is another example further supporting the intricate interplay between IAV and RNA decay machineries, used to rewire cellular gene expression in order to create a favorable environment for viral replication.

Download or read book Antiviral RNAi written by Ronald P. van Rij and published by Humana Press. This book was released on 2011-03-08 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Viruses and RNAi share an intricate relationship at many levels. RNAi is an important antiviral defense mechanism in plants and invertebrates, microRNAs – of viral or cellular origin – affect many aspects of virus biology, and replication of many, if not all, mammalian viruses can be suppressed by RNAi. Antiviral RNAi: Concepts, Methods, and Applications provides a collection of protocols for the analysis of viral small RNAs and natural antiviral RNAi responses as well as for the development and optimization of RNAi-based antiviral drugs. As RNAi is a central regulatory mechanism in the cell, the methods in this volume can also be applied out of the context of a virus infection. Divided into five convenient parts, this detailed volume reviews important basic concepts in the field of antiviral RNAi, provides experimental and bio-informatic tools for the analysis of small silencing RNAs, covers methods to biochemically dissect RNAi-based antiviral defense and viral counter-defense mechanisms, describes methods for the design, expression, and delivery of therapeutic antiviral siRNAs, and finally presents genome-wide RNAi approaches for the identification of factors involved in virus replication. Written in the highly successful Methods in Molecular BiologyTM series format, chapters contain introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and notes on troubleshooting and avoiding known pitfalls. Authoritative and accessible, Antiviral RNAi: Concepts, Methods, and Applications serves as an ideal guide for both novice and experienced researchers alike striving to dissect the role of RNAi in the viral life cycle or to further boost the development of novel therapeutics and experimental tools based on RNAi technology.

Download or read book Studies on the Functional Involvement of Cellular RNA binding Proteins in Translation Regulation of Picornaviruses and Hepatitis C Virus written by Eleni Tzima and published by . This book was released on 2006 with total page 306 pages. Available in PDF, EPUB and Kindle. Book excerpt:

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 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 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