Download or read book Functional Characterization of Conserved Domains Within the L Protein Component of the Vesicular Stomatitis Virus RNA dependent RNA Polymerase written by Summer E. Galloway and published by . This book was released on 2008 with total page 220 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Dependence of Vesicular Stomatitis Virus Polymerase Function on Structural Flexibility and Domain domain Interactions written by John Barragan Ruedas and published by . This book was released on 2013 with total page 89 pages. Available in PDF, EPUB and Kindle. Book excerpt: Gene expression and replication of nonsegmented negative strand (NNS) RNA viruses is performed by an RNA-dependent RNA polymerase. The polymerase large (L) protein catalyzes all functions including addition of a cap 1 (m7GpppNm) structure on nascent transcripts. Alignment studies show L proteins are modular consistent with a multi-domain protein. Reports of L functions being coupled suggest orchestrated interactions among its domains occur however specific domain interactions have not been experimentally confirmed. At the start of this dissertation virtually no structural information was known for NNS L proteins other than an EGFP-tolerant hinge region just upstream of a methyltransferase domain was discovered in the measles L protein. This dissertation shows a homologous hinge region is also present in the NNS prototype vesicular stomatitis virus (VSV) L protein and aims to gain fundamental insight into putative interactions involving domains near this hinge. Insertion of EGFP in VSV L produced a temperature sensitive polymerase in minigenome assays with minimal effects at 33°C but severe attenuation of RNA synthesis at 37°C. This phenotype was also observed in engineered recombinant virus encoding this modified polymerase. Moreover, this virus exhibited an inability to synthesize transcripts in vitro. The specific effect on RNA synthesis led to the proposal here that the insert restricts hinge movement thus impeding critical domain interactions. Four domains adjacent to the hinge were exchanged with VSV serotype counterparts to determine the effect on polymerase function. Exchanging the methyltransferase domain had no impact on L functions in minigenome assays and recombinant virus indicating it enjoyed a degree of autonomy. Exchange of the other domains however abolished RNA synthesis showing polymerase activity depends heavily on peptide sequences in these domains, supporting a model of interaction between these domains and other polymerase components. Combination exchanges of all four domains also yielded polymerase inactivity with one exception. Co-exchange of the methyltransferase and adjacent C-terminal domain partially rescued a defect that occurred by exchanging the C-terminal domain alone. This combination rescued replication activity substantially more than transcription (avg. 67% and 13%, respectively) providing evidence of an essential domain-domain interaction for RNA synthesis that is more favorable for replication.
Download or read book Roles of P and L Proteins in Regulating Vesicular Stomatitis Virus RNA Synthesis Analyzed by a Reverse Genetic Approach written by David Marc Canter and published by . This book was released on 1997 with total page 320 pages. Available in PDF, EPUB and Kindle. Book excerpt: Nonsegmented, negative strand RNA viruses are medically important in that they represent a broad class of infectious agents (three families - Rhabdoviridae, Paramyxoviridae and Filoviridae), including such afflictions as rabies (Rhabdoviridae) and Ebola virus (Filoviridae). Much of what we know about these viruses comes from studies carried out with vesicular stomatitis virus, the prototypic member of the family rhabdoviridae. VSV encodes a 29-kD phosphoprotein (P) and 241-kD large (L) protein which together form the polymerase complex responsible for transcription and replication. The mechanism regulating the switch between these two distinct modes of RNA synthesis is unknown and is the focus of this dissertation. Previous studies suggested involvement of an ATP-dependent function. Initially, a novel in vitro transcription reconstitution system was developed using plasmid encoded P and L proteins that both faithfully and efficiently mimicked in vitro transcription from disrupted virion cores. L protein was shown to be highly unstable (half-life 3 to 6 hours) when expressed alone and required P protein coexpression for its stability. Using the in vitro transcription reconstitution assay, constitutive phosphorylation of P protein was shown to be non-essential for transcription despite the claims of other labs; however, this modification appears to play a role in P multimerization and polymerase complex formation. L proteins containing mutations in a universally conserved NTP-binding motif were engineered and analyzed by an in vivo transcription/replication assay. All such mutants were shown to stimulate replication over wild-type L protein in a promoter-specific manner while they concomitantly down regulating transcription in a promoter-independent manner. Glycerol gradient analysis revealed that wild-type L protein, but not mutant L, displayed a higher sedimentation rate in the presence of ATP. Taken together, these results suggest that different modes of polymerization are likely dependent on a conformational switch of the L protein and that the ATP-bound form of the polymerase is a transcriptase while the unbound form is a replicase. These findings reveal a new mechanism by which polymerases are regulated and define a new target for antiviral strategies.
Download or read book Analysis of Conserved Domains in the ScVL1 RNA dependent RNA Polymerase written by Eric Routhier and published by . This book was released on 1999 with total page 284 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Roles of P and L Proteins in Regulating Vesicular Stomatitis Virus RNA Synthesis Analyzed by a Reverse Genetic Approach written by and published by . This book was released on 1997 with total page 286 pages. Available in PDF, EPUB and Kindle. Book excerpt: Nonsegmented, negative strand RNA viruses are medically important in that they represent a broad class of infectious agents (three families - Rhabdoviridae, Paramyxoviridae and Filoviridae), including such afflictions as rabies (Rhabdoviridae) and Ebola virus (Filoviridae). Much of what we know about these viruses comes from studies carried out with vesicular stomatitis virus, the prototypic member of the family rhabdoviridae. VSV encodes a 29-kD phosphoprotein (P) and 241-kD large (L) protein which together form the polymerase complex responsible for transcription and replication. The mechanism regulating the switch between these two distinct modes of RNA synthesis is unknown and is the focus of this dissertation. Previous studies suggested involvement of an ATP-dependent function. Initially, a novel in vitro transcription reconstitution system was developed using plasmid encoded P and L proteins that both faithfully and efficiently mimicked in vitro transcription from disrupted virion cores. L protein was shown to be highly unstable (half-life 3 to 6 hours) when expressed alone and required P protein coexpression for its stability. Using the in vitro transcription reconstitution assay, constitutive phosphorylation of P protein was shown to be non-essential for transcription despite the claims of other labs; however, this modification appears to play a role in P multimerization and polymerase complex formation. L proteins containing mutations in a universally conserved NTP-binding motif were engineered and analyzed by an in vivo transcription/replication assay. All such mutants were shown to stimulate replication over wild-type L protein in a promoter-specific manner while they concomitantly down regulating transcription in a promoter-independent manner. Glycerol gradient analysis revealed that wild-type L protein, but not mutant L, displayed a higher sedimentation rate in the presence of ATP. Taken together, these results suggest that different modes of polymerization are likely dependent on a conformational switch of the L protein and that the ATP-bound form of the polymerase is a transcriptase while the unbound form is a replicase. These findings reveal a new mechanism by which polymerases are regulated and define a new target for antiviral strategies.
Download or read book Cumulated Index Medicus written by and published by . This book was released on 1997 with total page 1860 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Research Advances in Rabies written by and published by Academic Press. This book was released on 2011-07-13 with total page 487 pages. Available in PDF, EPUB and Kindle. Book excerpt: Volume 79 of Advances in Virus Research focuses on developments surrounding rabies, an ancient disease that remains a prominent public health problem for humans. This volume highlights important research advances extending from our understanding of how the rabies virus replicates and assembles to how the disease can be prevented and treated in humans and how rabies can be controlled in wildlife hosts. Experts in the field provide insightful and up-to-date chapters that summarize our current state of knowledge in diverse aspects of this very interesting and important viral disease. - Contributions from leading authorities and industry experts - Informs and updates on all the latest developments in the field
Download or read book Dissertation Abstracts International written by and published by . This book was released on 2008 with total page 886 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Structural and Functional Characterization of the Phosphoprotein Subunit of the Sendai Virus RNA dependent RNA Polymerase written by Mary Catherine Bowman and published by . This book was released on 1997 with total page 340 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 Viral Polymerases written by Satya Prakash Gupta and published by Academic Press. This book was released on 2018-10-29 with total page 498 pages. Available in PDF, EPUB and Kindle. Book excerpt: Viral Polymerases: Structures, Functions and Roles as Antiviral Drug Targets presents in-depth study information on the structure and functions of polymerases and their roles in the lifecycle of viruses, and as drug targets. Viral polymerases constitute a vital component in the lifecycle of many viruses, such as human immunodeficiency virus (HIV), hepatitis viruses, influenza virus, and several others. They are essentially required for the replication of viruses. Thus, the polymerases that can be found in viruses (called viral polymerases) represent favorable targets for the design and development of antiviral drugs. - Provides comprehensive, state-of-the-art coverage on virus infections, the virus lifecycle, and mechanisms of polymerase inhibition - Analyzes the structure-activity relationships of inhibitors of each viral polymerase - Presents a consistent and comprehensive coverage of all aspects of viral polymerases, including structure, function and their role as antiviral drug targets
Download or read book Methylation written by Anica Dricu and published by Inst za onkologiju i radiol. This book was released on 2012-11-28 with total page 311 pages. Available in PDF, EPUB and Kindle. Book excerpt: Alterations in the normal DNA methylation processes are known to have major consequences for embryonic development and are associated with congenital defects, autoimmunity, aging and malignant transformation. The main purpose of this book is to provide information about the importance of methylation mechanisms in human health and disease. The book, covers the basic mechanism of DNA and protein methylation, aiming at the advanced undergraduate and graduate biomedical students and researchers working in the epigenetic area. The textbook chapters provide background as well as advanced information in the methylation area. On the other hand, it provide readers with both classical and relevant recent discoveries that have been made in the field, pointing out pathways where questions remain.
Download or read book Negative Strand RNA Virus written by Ming Luo and published by World Scientific. This book was released on 2011 with total page 323 pages. Available in PDF, EPUB and Kindle. Book excerpt: Ch. 1. Overview of negative-strand RNA viruses / Biao He -- ch. 2. Rhabdovirus entry into the host cell / Aurelie Albertini and Yves Gaudin -- ch. 3. Virus entry : parainfluenza viruses / Masato Tsurudome -- ch. 4. What controls the distinct VSV RNA synthetic processes of replication and transcription? / Gail Williams Wertz, Summer E. Galloway and Djamila Harouaka -- ch. 5. mRNA capping by vesicular stomatitis virus and other related viruses / Tomoaki Ogino and Amiya K. Banerjee -- ch. 6. Structural disorder within the measles virus nucleoprotein and phosphorprotein : functional implications for transcript and replication / Sonia Longhi -- ch. 7. Biochemical and structural insights into vesicular stomatitis virus transcription / Amal A. Rahmeh and Sean P.J. Whelan -- ch. 8. Transcription of vesicular stomatitis virus RNA genome / Debasis Panda and Asit K. Pattnaik -- ch. 9. Assembly of vesicular stomatitis virus / Ming Luo, Todd J. Green and Z. Hong Zhou -- ch. 10. Paramyxovirus budding mechanisms / Megan S. Harrison, Takemasa Sakaguchi and Anthony P . Schmitt -- ch. 11. Virus-host interaction by members of the family rhabdoviridae and filoviridae / Douglas S. Lyles -- ch. 12. Paramyxovirus and rig-like helicases : a complex molecular interplay driving innate immunity / Denis Gerlier -- ch. 13. The molecular and cellular biology of emerging bunyaviruses / John N. Barr -- ch. 14. Ebolaviruses : what we know and where we are on potential therapeutics / Peter Halfmann, Gabriele Neumann and Yoshihiro Kawaoak
Download or read book Measles Virus Nucleoprotein written by Sonia Longhi and published by Nova Publishers. This book was released on 2007 with total page 180 pages. Available in PDF, EPUB and Kindle. Book excerpt: Measles virus possesses a non segmented, single stranded, negative sense RNA genome that is encapsidated by the nucleoprotein to form a helical nucleocapsid. This ribonucleoproteic complex is the substrate for both transcription and replication. The RNA-dependent RNA polymerase binds to the nucleocapsid template via its co-factor, the phosphoprotein. This book focuses on the main structural information available on the nucleoprotein, showing that it consists of a structured core (NCORE) and of an intrinsically disordered C-terminal domain (NTAIL). The functional implications of the disordered nature of NTAIL are discussed in light of the ability of disordered regions to establish interactions with multiple partners, thus leading to multiple biological effects. Indeed, beyond the phosphoprotein, NTAIL also interacts with cellular partners, including the major heat shock protein, hsp72, the interferon regulator factor 3, IRF3, and a yet unidentified cellular receptor referred to as NR. This book consists of two chapters devoted to the general functions of the nucleoprotein in transcription and replication and to a detailed overview of its structural properties, and of three chapters focused on the functional relevance of the interaction between NTAIL and its various intracellular and extracellular partners.
Download or read book Rabies written by Anthony R. Fooks and published by Academic Press. This book was released on 2020-05-05 with total page 732 pages. Available in PDF, EPUB and Kindle. Book excerpt: Rabies: Basis of the Disease and Its Management, Fourth Edition is an authoritative reference on the current status of rabies, including the virological, clinical, and public health aspects and management recommendations. Rabies remains one of the most important global public health problems worldwide. Although many important developments have been made over the past century to combat this disease, rabies has become a re-emergent infection in the resource-constrained countries. The Fourth Edition updates this classic reference with comprehensive coverage of the molecular virology, pathogenesis, immunology, vaccines, public health aspects, and epidemiology of rabies and is completely revised, with new chapters that will cover historical developments in rabies intervention strategies, the evolution of rabies virus, modeling rabies control, and on the strategy for rabies elimination. Rabies, Fourth Edition, provides physicians, veterinarians, public health advisors, epidemiologists, and research scientists with a single source for authoritative and up-to-date information on the diagnosis, treatment, control, and prevention of this fatal infectious virus. Edited by renowned researchers in this subject and has gathered a team of experts to detail the science, treatment, and control of rabies Completely revised, the Fourth Edition presents rabies as a re-emergent infection with emphasis on a global perspective of the disease Includes new chapters the evolution of the rabies virus and on modeling rabies control and includes many full-color figures that highlight important information
Download or read book Viral Replication Enzymes and their Inhibitors Part B written by and published by Academic Press. This book was released on 2021-12-01 with total page 430 pages. Available in PDF, EPUB and Kindle. Book excerpt: Viral Replication Enzymes and their Inhibitors, Part B, Volume 50 in The Enzymes series, highlights new advances in the field, with this new volume presenting interesting chapters on a variety of topics surrounding enzymes. - Provides the authority and expertise of leading contributors from an international board of authors - Presents the latest release in The Enzymes series
Download or read book Advances in Virus Research written by Karl Maramorosch and published by Gulf Professional Publishing. This book was released on 2005-11-16 with total page 290 pages. Available in PDF, EPUB and Kindle. Book excerpt: Published since 1953, Advances in Virus Research covers a diverse range of in-depth reviews providing a valuable overview of the current field of virology. In 2004, the Institute for Scientific Information released figures showing that the series has an Impact Factor of 2.576, with a half-life of 7.1 years, placing it 11th in the highly competitive category of Virology.
