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.
