The Influenza Viruses

The Influenza Viruses

by Robert M. Krug (Editor)

Paperback(Softcover reprint of the original 1st ed. 1989)

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Influenza virus is an important human pathogen, frequently causing widespread disease and a significant loss of life. Much has been learned about the structure of the virus, its genetic variation, its mode of gene expression and replication, and its interaction with the host immu­ nologic system. This knowledge has the potential of leading to ap­ proaches for the control of influenza virus. In addition, research on influ­ enza virus has led to important advances in eukaryotic molecular and cellular biology and in immunology. A major focus of this book is the molecular biology of influenza virus. The first chapter, which serves as an introduction, describes the structure of each of the genomic RNA segments and their encoded pro­ teins. The second chapter discusses the molecular mechanisms involved in the expression and replication of the viral genome. In addition to other subjects, this chapter deals with one of the most distinctive features of influenza virus, namely the unique mechanism whereby viral messenger RNA synthesis is initiated by primers deaved from newly synthesized host-cell RNAs in the nudeus. Among the most significant accomplish­ ments in influenza virus research has been the delineation of the three­ dimensional structure of the two surface glycoproteins of the virus, the hemagglutinin and neuraminidase. This has provided a structural basis for mapping both the antigenic sites and the regions involved in the major biological functions of these two molecules.

Product Details

ISBN-13: 9781461280941
Publisher: Springer US
Publication date: 10/08/2011
Series: The Viruses
Edition description: Softcover reprint of the original 1st ed. 1989
Pages: 450
Product dimensions: 6.69(w) x 9.61(h) x 0.04(d)

Table of Contents

1 Genes and Proteins of the Influenza Viruses.- I. Introduction.- A. Structure of the Genome.- II. RNA Segments 1, 2, and 3: The Three Polymerase-Associated Proteins Form a Complex to Transcribe RNA.- A. Three P Proteins.- B. PB1, PB2, and PA Gene Sequences.- C. Functions of the PB1, PB2, and PA Proteins.- D. P Proteins Form a Complex That Migrates to the Cell Nucleus.- E. Influenza B Virus P Proteins and RNA Segments.- F. Influenza C Viruses.- III. RNA Segment 4: Synthesis, Structure, and Function of the Hemagglutinin.- A. General Introduction to the Hemagglutinin.- B. RNA Segment 4 Gene Structure.- C. Three-Dimensional Structure of the Hemagglutinin.- D. Synthesis of HA, Co-translational and Post-translational Modifications, Oligomerization, and the Exocytotic Pathway.- E. Cleavage Activation.- F. Viral Entry and Membrane Fusion.- G. Influenza B Virus Hemagglutinin.- H. Influenza C Virus Glycoprotein.- IV. RNA Segment 5: The Nucleocapsid Protein Forms the Structural Monomer Unit of the Ribonucleoprotein Particles.- A. Structure of RNPs and Involvement in RNA Synthesis.- B. Properties of the Nucleocapsid Protein.- C. Nuclear Transport and Karyophilic Sequences.- D. RNA-Protein Interactions.- E. NP Is a Major Target for Cytotoxic T Lymphocytes.- F. Influenza B Virus NP Gene and Protein.- G. Influenza C Virus NP Gene and Protein.- V. RNA Segment 6: The Neuraminidase.- A. Neuraminidase Function.- B. Structure of Neuraminidase.- C. General Deductions from the Gene Sequence of Influenza A Virus NA.- D. Influenza A Virus Strain Similarities and Differences.- E. N-Terminal Signal Anchor.- F. Three-Dimensional Structure of NA.- G. Influenza B Virus Neuraminidase.- H. Influenza B Virus RNA Segment 6.- I. NB Glycoprotein of Influenza B Virus.- J. Effect of Mutations and Deletions in the Bicistronic mRNA for NB and NA.- K. Influenza C Virus.- VI. RNA Segment 7 of Influenza A Virus: Structure and Synthesis of the Membrane Protein (M1) and an Integral Membrane Protein (M2) from Unspliced and Spliced mRNAs.- A. RNA Segment 7 and Its mRNAs.- B. Membrane Protein (M1).- C. Influenza Virus M2 Protein Structure and Subcellular Localization.- D. Expression of M2 in Eukaryotic Cells from Cloned cDNA.- E. Characterization of a Monoclonal Antibody to the M2 Extracellular Domain.- F. Initial Interaction of M2 with Membranes.- G. Is M2 a Structural Component of Virions?.- H. Function of M2 in Infected Cells.- I. Effect of Amantadine Hydrochloride on M2.- J. Evolution of the Nucleotide Sequence of RNA Segment 7 and the Amino Acid Sequences of M1 and M2.- K. RNA Segment 7 of Influenza B Virus.- L. Membrane Protein of Influenza C Virus.- VII. Influenza A Virus RNA Segment 8: Unspliced and Spliced mRNAs Encode Nonstructural Proteins NS1 and NS2.- A. RNA Segment 8 and Its mRNAs.- B. NS1 Protein.- C. NS2 Protein.- D. RNA Segment 8 of Influenza B Virus: Unspliced and Spliced mRNAs Code for NS1 and NS2.- E. Influenza C Virus RNA Segment 7: Unspliced and Spliced mRNAs Code for NS1 and NS2.- References.- 2 Expression and Replication of the Influenza Virus Genome.- I. Introduction.- II. Viral mRNA Synthesis.- III. Template RNA Synthesis.- IV. Virion RNA Synthesis.- V. Regulation of Viral Gene Expression in Infected Cells.- VI. Interferon-Induced Mx Protein, a Specific Inhibitor of Influenza Virus Replication.- VII. Regulated Splicing of the Viral NS1 and M1 mRNAs.- VIII. Mechanisms for the Selective and Efficient Translation of Influenza Virus mRNAs.- References.- 3 Structure, Function, and Antigenicity of the Hemagglutinin of Influenza Virus.- I. Introduction.- II. Structure of Hemagglutinin.- III. Antigenic Variation.- A. Antigenic Shift.- B. Antigenic Drift.- C. The Importance of Receptor Specificity in Antigenic Change.- IV. Receptor Binding.- A. Structure of the Receptor-Binding Site.- B. The Binding Site of a Receptor-Binding Mutant.- V. Fusion Properties of Hemagglutinin.- A. Acid-Induced Conformational Change of Hemagglutinin.- VI. Conclusions.- References.- 4 Neuraminidase: Enzyme and Antigen.- I. Introduction.- A. Biological Properties.- B. Physical Characteristics.- C. Gene Structure.- II. Protein Structure.- A. Chemical Aspects.- B. Three-Dimensional Structure of Head.- III. Antigenic Structure.- A. Amino Acid Sequence Variation within Subtypes.- B. Antigenic Analysis with Antibodies.- C. Structure of Immune Complexes.- IV. Summary.- References.- 5 Membrane Insertion and Intracellular Transport of Influenza Virus Glycoproteins.- I. Introduction.- II. Entry of Influenza Glycoproteins into the Exocytic Pathway.- A. Co-translational Events.- B. Post-translational Processing in the Endoplasmic Reticulum.- C. Mutants of Hemagglutinin That Are Defective in Transport from the ER.- III. Protein Transport between the Endoplasmic Reticulum and the Golgi Apparatus.- IV. Transport and Processing within the Golgi Apparatus.- A. Organization of the Golgi Apparatus.- B. Movement of Influenza Virus Glycoproteins through the Golgi Apparatus.- C. Processing of Influenza Virus Oligosaccharides.- D. Role of Glucosylation of Influenza Virus Glycoproteins..- V. The Trans-Reticular Network.- A. Sorting of the Hemagglutinin and the Neuraminidase to the Apical Domain of Polarized Epithelial Cells.- B. Evidence for Proteolytic Processing of Certain Hemagglutinins by Cellular Proteases during Transport to the Cell Surface.- C. Hemagglutinins Defective in Transport from the Golgi Apparatus to the Cell Surface.- VI. Transport to the Cell Surface and Insertion into the Plasma Membrane.- VII. Summary and Perspectives.- References.- 6 Structure of Defective-Interfering RNAs of Influenza Viruses and Their Role in Interference.- I. Introduction.- II. Nature of the DI Particle Genome.- A. Generation and Amplification of Influenza Virus DI Particles.- B. Analysis of DI RNA by PAGE.- C. Primary Structure of DI RNA.- III. Generation of Influenza Virus Subgenomic/DI RNA.- IV. Evolution of DI RNAs.- V. Replication, Transcription, and Translation of DI RNAs.- A. Transcription of DI RNAs.- B. Translation of DI Virus-Specific mRNA.- VI. Mechanism of Interference.- A. Effect of DI Virus Particles on the Transcription and Replication of Standard RNAs.- B. Effect of DI Particles on the Translation of Standard Polypeptides.- C. Possible Role of DI Virus-Specific Polypeptides in Interference.- D. Partial Reversal of DI Virus-Mediated Interference with Increasing Concentration of Standard Virus Particles.- E. Role of DI RNA in Virus Assembly.- F. Summary.- VII. Possible Role of Influenza DI Particles in Modulating Viral Pathogenesis.- VIII. Possible Role of DI Particles in Virus Evolution.- IX. Summary and Conclusion.- References.- 7 Variation in Influenza Virus Genes: Epidemiological, Pathogenic, and Evolutionary Consequences.- I. Introduction.- II. Influenza Viruses in Humans.- III. Homology of Influenza A, B, and C Viruses.- A. HA/HE Genes.- B. NP Genes.- C. M Genes.- D. NS Genes.- E. Conclusion.- IV. Variation in Influenza A Viruses.- A. Reassortants.- B. Animal Viruses Become Virulent for Humans.- C. Re-emergence of Previously Circulating Strains.- D. Genetic Drift.- E. Evolution of Influenza A Viruses.- V. Variation in Influenza C Viruses.- A. HE Genes.- B. NS Genes.- C. Evolution of Influenza C Viruses.- VI. Variation in Influenza B Viruses.- A. HA Genes.- B. NS Genes.- C. Comparison of Evolutionary Pattern of Influenza A, B, and C Viruses.- VII. Genetic Basis of Pathogenicity.- A. Pathogenicity Is Multigenic.- B. HA Genes.- C. NA Genes.- D. M Genes.- VIII. Comparison of Variation among Different RNA Viruses.- A. Tissue-Culture Studies.- B. Variation in Nature of Human RNA Viruses.- References.- 8 Specificity and Function of T Lymphocytes Induced by Influenza A Viruses.- I. Introduction.- A. Why Study T-Lymphocyte Responses to Influenza Virus?.- B. Background Information.- II. General Properties of Antiviral T-Lymphocyte Responses.- A. Assessing Recognition of Viral Antigens by T Lymphocytes.- B. Induction of Influenza Virus-Specific T Lymphocytes.- III. Specificity and Function of Anti-influenza Virus TH.- A. Specificity of TH.- B. Antigen Processing as a Requirement for TH Recognition of Influenza Virus Components.- C. Role of TH in Antiviral Immunity.- IV. Specificity and Function of Anti-influenza Virus TC.- A. Specificity of TC.- B. Role of TC in Antiviral Immunity.- V. Conclusions.- References.

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