The Molecular Biology of Poliovirus

ISBN-13: 9783709174678 / Angielski / Miękka / 2011 / 590 str.

F. Koch; G. Koch

Opis

Years ago when we were asked to write a book on the present-day knowledge of the molecular biology of poliovirus, we did not expect that such an apparently simple task could involve so much time and effort. Our writing was hampered by the fact that both of us are full time "workers," so that this monograph is mainly a spare time expedience. The main attention of this book focuses on a detailed review of the molecular biology of poliovirus and especially on the advances of the last decade; medical and environmental aspects are only briefly mentioned. Observations from older studies are considered in view of more recent information. Some of the older ob servations provided fundamental insights and paved the way for present day research; too often such data has been neglected or independently rediscovered. Today, poliovirus research has again attracted considerable interest. High points gained within the last few years were the elucidation of the complete nucleotide sequences of the RNAs of the three poliovinls serotypes and the corresponding vaccine strains, the demonstration of genome evolution during transmission of poliovirus in an epidemic, further characterization of the antigenic sites on the virus particle and of the antigenic drift, characterization of alternate conforma tional states of the virion capsid, the development of monoclonal antibodies against some of the virus proteins, observations on the role of the plasma membrane, cytoskeleton, and cytoplasmic membranes as mediators in the virus induced redirection of the synthetic machinery of the host cell, and characteriza

Spis treści

I: The Poliovirus.- 1. History.- I. Introduction.- II. Early History-Occasional Nonepidemic Cases of Poliomyelitis.- III. The 18th and 19th Centuries: Polioepidemics, Poliomyelitis Is Described as a Clinical Entity.- IV. Early 20th Century: Research on Polio Begins, Virology Is still a Clinical Discipline.- V. The Development of Vaccines Against the Poliomyelitis Virus.- VI. The Fifties and the Advent of Molecular Biology.- VII. Advances in Polio Research During the Past Two Decades.- 2. Classification.- I. General Considerations.- A. Nature of the Genome.- B. The Cryptogram.- II. The Distinguishing Features of Picornaviruses.- III. Comparison of Different Picornavirus Genera.- A. Disease Aspects.- B. Serotypes.- C. Physical Properties.- D. Relative Relatedness to Polioviruses.- 3. Composition and Structure of the Virion.- I. Introduction.- II. Composition and Physical Properties of the Virion.- III. Overall Architecture of the Viral Capsid.- A. Building Blocks.- 1. Functional Requirements.- 2. Biological Arguments of Building Block Economy and Efficiency of Assembly.- 3. Thermodynamic Forces and Structural Consequences.- B. The Geometric Design: The Icosahedron.- 1. Helical Tubes Versus Spherical Shells.- 2. Cubic Symmetries, the Platonic Polyhedra.- 3. The Icosahedron.- a) Advantages of Icosahedral Symmetry.- b) Limitations of the Icosahedral Skeleton as a Model for Virus Structure.- c) Related Regular Polyhedra with Icosahedral Symmetry.- d) The Bonding Pattern of an Icosahedral Lattice.- C. Experimental Evidence that the Poliovirus Capsid Is an Icosahedral Lattice.- 1. X-Ray Diffraction Studies.- 2. Electron Microscopic Observations.- 3. Resolving the 32 or 60 Capsomers Controversy.- 4. Similar Construction Principles for Picornaviruses and the Small Plant Viruses.- IV. Characterization of the Building Blocks: The Capsid Proteins.- A. Separation and Identification.- B. Amino Acid Composition and Sequence.- C. Microheterogeneity.- V. Relative Localization of the Viral Proteins in the Capsid and Bonds Involved.- A. General Reflections.- 1. Geometric Restrictions.- 2. Structural Principles Borrowed from Plant Picornaviruses.- 3. Implications for the Capsid Features of Poliovirus: The Concept of a Rigid Capsid Backbone and Variable Surface Protrusions.- B. Experimental Results.- 1. Specific Chemical Modifications of Capsid Proteins.- 2. Chemical Crosslinking of Capsid Proteins.- 3. UV Irradiation of Poliovirus.- VI. The Dissociation of Poliovirus.- A. Breakdown During Preparatory Procedures for Electron Microscopy.- B. Alkaline Degradation.- C. Heat Degradation.- D. Guanidine Degradation.- E. Urea Degradation.- F. Reassociation of Poliovirus from Products of Urea Degradation.- G. Conclusions.- VII. Conformational Forms of the Poliovirus Capsid.- A. Poliovirus Capsid Structures During Early Interactions with the Host Cell and upon Experimentally Induced Disruption: Two Conformational States of the Shell.- B. Viral Structures During Maturation.- C. Two Distinct, Reversibly Interconvertible Conformational States of Intact Poliovirions.- D. Conformational Alterations Monitored by Changes in the Intrinsic and Induced Fluorescence of Poliovirus Components.- E. Dense Particles.- F. Possible Functions of the Alternate Conformational States of the Poliovirus Capsid.- VIII. Antigenicity.- A. The Main Poliovirus Antigenic Sites: The D- and C-Antigenic States.- 1. Attempts to Identify the C- and D-Antigenic Determinants in Terms of the Constituent Capsid Proteins with Polyclonal Antisera.- 2. Studies with Monoclonal Antibodies.- B. Other, Minor Antigenic Sites on Poliovirus.- C. Serodifferentiation of Polioviruses.- IX. Summary.- A. Composition.- B. Structure.- C. The Capsid Proteins.- 1. Number of Peptides and Type of Association on the Structure Units.- 2. Relative Localizations.- 3. Heterogeneity.- D. Two Conformational States of the Capsid.- E. Antigenicity.- 4. Structure and Function of the Genome.- II. Genome Structure.- A. Characteristic Features.- B. Structural Organization.- C. Secondary Structure.- D. The Genome-Linked Protein VPg.- III. Nucleotide Sequences.- A. Oligonucleotide Mapping.- B. Cloning of Poliovirus cDNA.- C. The Consensus Sequence of Poliovirus Type I.- D. Terminal Sequences.- 1. 5? End Sequences.- 2. 3? End Sequences.- 3. The Poly (A) Tract.- E. Features of the Coding Region.- 1. Codon Usage.- 2. Cleavage Signals for Proteolytic Processing.- IV. Genome Products and Gene Order.- A. Mapping of the Genome Products on the Polioviral Genome.- 1. Relatedness of Viral Proteins: Tryptic Peptide Analysis.- 2. Biochemical Mapping.- 3. The Genome Map as Deduced from Genetic Studies.- B. Function of the Viral Proteins.- 1. The P-1 Proteins: Coat-Proteins, Proteinkinase, Shut-Off of Protein Synthesis.- 2. The P-2 Proteins: Guanidine Sensitivity, VP0 Protease.- 3. The P-3 Proteins: glu/gly Protease, VPg Replicase, Cytophathic Effect.- V. Genomic Variation of Polioviruses.- VI. Genetics.- A. Mutations.- B. Mutant Types.- 1. Temperature Sensitive Mutants.- 2. Structural Markers.- 3. Non Structural Markers.- C. Genetic Recombination.- D. Mechanism of Recombination.- VII. Summary.- II: The Replication of Poliovirus.- 5. Introduction.- I. The “Life-Cycle” of Poliovirus.- II. Timecourse of Poliovirus Replication.- III. The Host Cell.- A. Constituents of the Cell.- B. The Nucleus.- C. The Plasma Membrane.- D. The Ionic Environment.- E. The Cytoskeleton.- F. Intracellular Membranes.- G. The Cell Cycle.- H. Employment of the Metabolic Machinery of the Host Cell by the Virus.- IV. Some Speculations on Abortive Infections of Poliovirus..- 6. Morphological Alterations of the Host Cell as an Essential Basis for Poliovirus Replication.- I. Introduction.- II. Microscopic Oberservations.- A. Light Microscopy.- B. Electron Microscopy.- 1. The Nucleus.- 2. Ribosomes.- 3. “Viroplasm”.- 4. Alterations of Intracellular Membranes.- a) Nuclear “Extrusions”.- b) Membraneous Cisternae.- c) Biochemical Aspects of Membrane Formation.- 5. Changes in the Cytoskeletal Framework.- 6. Assembly and Release of Progeny Virions.- 7. Lysosomes and Autophagic Vesicles.- 8. Inhibitors of Morphological Alterations.- III. Speculations on the Function of Compartmentalization in Virion RNA Synthesis and Assembly.- A. Concerning the Mode of Vesicle Formation.- B. Concerning the Relative Localization of RNA Synthesis and Virion Assembly with Respect to the Vesicle Membrane.- IV. Poliovirus induced Alterations in Functions of the Plasma Membrane, in the Intracellular Ionic Environment, and in Cell Size.- A. Membrane Changes Accompanying Adsorption and Penetration of Poliovirus.- B. Membrane Alterations Accompanying Virus Replication at the Maximal Rate.- V. Summary.- 7. Early Interactions of Virus and Host Cell.- I. Introduction.- A. Overview and Definition of Terms.- B. The Superposition of Abortive and Productive Pathways in Infection.- II. Adsorption and Attachment.- A. The Reaction Partners.- 1. The Virus Particle.- 2. The Virus Receptor Complex on the Host Cell.- a) Properties of the Poliovirus Receptor.- b) Other Functions and Components of the Receptor Complex.- c) Number of Attachment Sites/Cell.- d) Specificity and Genetics of Virus Receptors.- B. The Interaction of Poliovirions with the Host Cell Membrane.- 1. Adsorption.- 2. Attachment.- 3. Response of the Plasma Membrane.- a) Changes in Membrane Fluidity and Capping of Viruses.- b) Changes in Membrane Permeability and Membrane Potential.- c) Interaction with Modifying and Stabilizing Membrane Components.- III. Penetration of Virus Particles into the Cell: Insertion and Phagocytosis.- IV. Uncoating: A Multistep Process.- A. Possible Steps and Sites of Uncoating.- B. The Fate of the Parental Capsid Proteins.- V. Infection of Cells Lacking Receptors.- A. Introduction.- B. Adsorption of Viral RNA to Cells.- C. Penetration of Isolated Viral RNA into Cells.- 1. RNA-Penetration by Passive Influx of RNA.- 2. Stimulation of Active Uptake of Viral RNA.- 3. Entrance of Poliovirus RNA into Cells Via Lipid Vesicles (Liposomes).- D. Cellular Competence for Infection by Viral RNA.- 1. Optimal Conditions for the Use of Polycations.- 2. Relationship Between RNA Concentration and Yield of Infections Centers.- 3. The Combined Effect of Dimethylsulfoxide and DEAEDextran on the Competence of Cells for Infection by Viral RNA.- 4. Competence of HeLa Cells for Infection by Viral RNA at Different Stages in a Cell Growth Cycle.- E. Conclusions.- VI. Summary.- 8. Translation of the Viral Genome.- I. Mammalian Protein Synthesis.- A. The Protein Synthesizing Machinery.- 1. Ribosomes.- a) Structure and Composition.- b) Monosomes and Polysomes.- c) Free and Membrane Bound Polysomes.- 2. mRNA.- a) The Cap.- b) The 5? Terminal Untranslated Region.- c) The 3? Terminal Untranslated Region and the Poly A Tract.- d) Monocistronic mRNAs and Potential Internal Initiation Sites.- e) mRNPs.- 3. Initiation Factors and the Process of Initiation.- 4. Elongation and Termination of Translation.- 5. Cotranslational Processing and Membrane Insertion of Nascent Polypeptide Chains.- B. The Regulation of Protein Synthesis.- 1. The Role of Culture Conditions.- 2. Competition Between mRNAs.- a) The Role of mRNA Concentration.- b) Relative Translational Efficiencies of mRNAs.- c) The Role of Limiting Initiation Components.- 3. Alteration or Inactivation of the Cap Binding Protein and Other Initiation Factors.- 4. Modification of Ribosomes.- 5. The Role of Uncharged tRNA.- 6. Transfer of mRNAs Between Untranslatable and Translatable Pools.- 7. Control of Free and Membrane Bound Pools of Ribosomes.- II. Translation of the Poliovirus Genome.- A. Overview and Introduction.- B. Translation of Poliovirus RNA in Cell Free Extracts.- 1. General Comments.- 2. Initiation of in vitro Translation.- 3. In vitro Elongation and Termination.- C. The Additional Complexity of in vivo Translation During Infection.- 1. The Shut-Off Phenomenon.- a) The Activation of an Inherent Host-Cell Regulatory Mechanism.- b) Competition Between Viral and Host Cell mRNAs.- c) The Role of Ionic Disturbances and Membrane Leakiness.- d) Alterations of Initiation Factors or Ribosomes.- e) The Role of Virus-Specific Factors in Mediating the Shut-Off.- f) In Summary, a Concert of Mechanisms with a Purpose.- 2. Non-Uniform Synthesis of Viral Proteins.- 3. The Role of Interaction Between Poliovirus Proteins and Intracellular Membranes.- 4. Distribution of Viral Proteins.- 5. Protein Processing.- a) The Role of Cleavage.- b) Types of Cleavages.- c) Types of Proteases.- d) Role of Cleavage in RNA-Replication.- e) Interference with Protein Processing.- f) The Effect of Guanidine on the Processing of Polioviral Proteins.- III. Summary.- 9. Replication of the Viral RNA.- I. Introduction.- II. Isolation and Characterization of Virus Specific RNAs Isolated from Infected Cells.- A. Preparation and Purification of Poliovirus Specific RNAs.- B. Properties of Poliovirus Specific RNAs.- 1. The Single-Stranded Viral RNA.- 2. The Replicative Form-RNA.- 3. The Replicative Intermediate-RNA.- 4. Double Stranded Forms of RNA-Extraction Artefacts?.- III. Time Course and Kinetics of Synthesis of Virus Specific RNAs.- A. The Onset of RNA Synthesis.- B. The Exponential Phase: cRNA ? mRNA ? cRNA.- C. The Linear Phase: cRNA ? vRNA, mRNA.- D. Cessation of RNA Synthesis.- IV. The Sites of RNA Synthesis.- V. The Viral RNA-Polymerases.- A. The Crude Replication Complex: Synthesis of Plus Strand RNA.- B. Soluble Replicase(s): Synthesis of Minus Strand RNA.- VI. The Effects of Guanidine on Poliovirus Replication.- VII. Some Thoughts on the Mode of RNA Replication.- A. Initiation of Viral RNA Synthesis.- B. Elongation of Viral RNA Replication.- C. Inhibition of Host Nuclear Functions.- D. On the Infectivity of RF-RNA.- E. Regulation of Viral RNA Synthesis.- VIII. Summary.- 10. Assembly of the Virion.- I. The Cytoplasmic Sites of Assembly-Virus-Induced Intracellular Membranes.- A. Electron Microscopic Observations.- B. Biochemical Approaches.- II. Subviral Particles in the Infected Cell-Potential Assembly Intermediates.- A. Overview.- B. NCVP1a and the 5S Protomer.- C. The 14S Pentamer.- D. The 55S Particle.- E. The 80S Shell.- F. Ribonucleoprotein Particles.- 1. The Slow Sedimenting (80S) RNPs.- 2. The 125S and 150S Provirion(s).- 3. Association of RNPs with the Replication Complex in Smooth Membranes.- III. Assembly Kinetics.- A. Chasing of Radioactive Precursors: Nucleosides and Amino Acids.- B. Assembly of Isolated Subviral Particles in vitro.- 1. Self Assembly of Isolated Subunits.- 2. Assembly-Enhancing Activity in Extracts of Infected Cells.- C. Studies with Inhibitors of Assembly.- 1. Reversible Inhibition of Assembly by Py-11.- 2. Studies with the Assembly Inhibitor Guanidine.- 3. Inhibition of Poliovirus Maturation Under Hypotonic Culture Conditions.- 4. Assembly Defective Mutants.- IV. The Individual Steps of Assembly.- A. Principles of Assembly.- B. Formation, Activation, and Assembly of the 5S Protomer.- C. Activation and Assembly of the 14S Pentamer.- D. Encapsidation of the Viral RNA.- 1. Condensation of the Viral RNA.- 2. Formation of the RNP.- a) Assembly Around an RNP Core.- b) Insertion of RNA into a Procapsid.- 3. Stepwise Condensation of the RNPs.- 4. The Possible Role of Mg++.- E. The Final Morphogenetic Cleavage.- V. Summary.- 11. Conclusions.- Appendix I: Laboratories Engaged in Poliovirus Research.- Appendix II: Poliovirus Models.- A. A Paper Model of a Prototype Picornavirus.- B. The Apple Model of Poliovirus.- Appendix III: The Geometry of Isometric Polyhedra.- A. The Platonic Polyhedra.- a) Models.- b) Characteristics.- c) Duality.- d) The Golden Proportion.- e) Geometric Restriction of the Maximal Number of Subunits.- B. Other Icosahedron-Related Polyhedra.- a) Characteristics.- b) The Triangulation-Number-Classification of Icosahedral Lattices.- Appendix IV: Complete Nucleotide and Amino Acid Sequences of Poliovirus Type 1, 2 and 3.- References.