Latency: an Interaction of Herpesviruses with Their Hosts.- 5. Genetic Engineering of HSV Genomes.- A. Basic Strategy.- B. Properties of the HSV TK.- C. Construction of Novel HSV Genomes.- The AlphaTK/miniMu System.- D. The Minimum and Maximum Sizes of HSV Genomes that Can Be Packaged.- E. Sites and Sequences Not Essential for Growth in Cell Culture.- F. Insertion of HSV and Foreign Sequences into HSV Genome.- G. Requirements for the Expression of Foreign Genes.- H. Stability of Genetically Engineered HSV-1 Genomes...- Cell-specific restrictions.- Equalization of genetically related duplicated genes.- Insert-dependent defective genomes.- Priviledged sites.- Acknowledgements.- 6. References.- Section V: the Maratea Conference.- The Maratea Conference.- List of Participants.
Overview of the Cycle.- Penetration.- Primary Transcription.- Translation of the Glycoprotein mRNA.- Posttranslational Processing of Viral Proteins.- The NS Protein.- Viral RNA Replication.- Viral Maturation.- B. Transcription.- Single vs Multiple Initiation Events.- C. The Polymerase Complex and Its Multiple Functions.- Posttranscriptional Processing of Viral mRNAs.- "Cap" Formation.- Polyadenylation.- D. Replication.- E. Generation of Defective Interfering Particles.- F. Viral Mutations.- 4. Relevant Problems in Rhabdovirology.- 5. References.- 12: The Molecular Biology of Paramyxoviruses.- 1. The Paramyxovirus Family.- A. Classification.- 2. The Virion.- A. The Viral Genome.- 3. The Replicative Cycle.- A. Primary Transcription and Translation.- B. Genome Replication (Amplification).- C. Genetic Stability of Paramyxoviruses and Their Evolution.- 4. The Generation and Biology of Defective Interfering Particles.- 5. References.- 13: Influenza Viruses: Genome Structure, Transcription and Replication of Viral RNA.- 1. Structure of the Influenza a Particle.- 2. Structure of the RNA Genome.- A. RNA Segments 1, 2 and 3: Polymerase Proteins PB1, PB2 and PA.- B. RNA Segment 4: Hemagglutinin Protein (HA).- C. RNA Segment 5: Nucleoprotein (NP).- D. RNA Segment 6: Neuraminidase (NA).- E. RNA Segment 7: Matrix Protein (Ml); Nonstructural Protein (M2).- F. RNA Segment 8: Nonstructural proteins (NSl and NS2).- 3. Transcription and Replication of Influenza a Virus RNA.- A. Transcriptional Controls.- B. Mechanism of Viral mRNA Synthesis.- B. Synthesis of Full-length cRNA Transcripts.- D. Synthesis of vRNA (Replication).- E. Effect of Interferon on Influenza Virus Replication.- 4. References.- 14: The Molecular Biology of Arenaviruses.- 1. Molecular Attributes of the Arenaviridae.- A. The Members of the Arenaviridae.- B. Arenavirus Structural Components.- C. The Infection Cycle.- D. The Genetic Attributes of Arenaviruses.- E. The Ambisense Coding Arrangement of the S RNA Species.- F. How an Ambisense Genome May Arise?.- 2. References.- 15: The Reovirus Family at the Molecular Level.- A. General Characteristics of Reoviridae.- Virion symmetry.- Enzymic component.- B. General Properties of Mammalian Reoviruses: The Model System.- 1. The Reovirus Virions.- A. Morphology.- The spikes.- Top component.- B. Protein Constitution.- Proteolytic cleavage.- Post-translational modifications.- C. Nucleic Acid Composition.- The composite RNA complement.- The single-stranded oligonucleotides.- D. Virion-associated Enzymes.- Location of the enzymes.- 2. Biological Functions of Reovirus-Coded Peptides.- A. Structural Proteins.- Gene shuffling and the genetic approach.- Function assignement.- B. Non-structural Proteins.- 3. Reovirus Replication Cycle.- A. Virus Adsorption.- B. Penetration and Uncoating.- The two-step model.- C. Viral Transcription.- Early and late transcription.- Pre-early and early transcription.- Pre-early/early transition.- Regulation of RNA synthesis.- D. Virus Replication.- Location of RNA synthesis.- E. Translation of Reovirus mRNAs.- Intrinsic translation ability of reovirus mRNAs.- Translation of host vs. reovirus mRNAs.- F. Virion Morphogenesis and Maturation.- RNA segment selection.- The intermediate structures.- 6. Concluding Remarks.- Acknowledgements.- 7. References.- 16: The Molecular Biology of Retroviruses.- 1. Classification.- 2. Structure of the Virions.- A. Morphology.- A-type particles.- B-type particles.- C-type particles.- D-type particles.- B. Protein Components.- The reverse transcriptase.- Envelope proteins.- C. The RNA Genome.- The R Regions.- The U5 region.- The L region.- The U3 region.- D. Oncogenes.- Definition.- Historical background.- Src.- V-sis.- V-fms.- erb.- Oncogenes in non virus-induced tumors.- Mechanism(s) of action of oncogenes.- 3. The Replication Cycle.- A. The Synthesis of the DNA Provirus.- B. Expression of the Viral Genome.- Regulatory sequences.- Synthesis of the gag gene products.- The pol gene protein.- The env gene proteins.- v-onc.- C. Virion Assembly.- 4. Molecular Basis of Pathology.- A. Non-Pathogenic Infections and Endogenous Retroviruses.- B. Acute Neoplasms.- C. Chronic Neoplasms.- D. Tumors Induced by Mouse Mammary Tumor Viruses.- 5. Human T Leukemia Viruses.- A. HTLV Genome.- B. Products of HTLV Genome.- C. Cellular Pathology.- 6. Concluding Remarks.- Acknowledgements.- 7. References.- 17: The Molecular Biology of Hepatitis B Virus.- 1. The HBV Carrier State.- 2. The Virion Particle.- A. Genome Organization.- B. Structural Genes.- C. HBV RNA Transcripts.- D. HBV Gene Products.- E. Regulatory Sequences.- 3. Hepadnavirus Replication.- A. Similarities between Hepadna Viruses and Retroviruses in Genome Organization and Replication Mechanisms..- B. Cis- and Trans-acting Factors in Viral Gene Expression..- C. HBV DNA in Serum.- D. Replicating Versus Nonreplicating States of Persistent HBV Infection.- 4. HBV-DNA Integration in Hepato Cellular Carcinoma.- A. Possible Role of Chemical Carcinogens.- B. Unifying Hypothesis Relating Viral and Nonviral Factors in Hepatic Oncogenesis.- Acknowledgements.- 5. References.- 18: The Biology of the Papillomaviruses.- 1. Biological Properties.- A. Virus Growth.- B. Transforming Papillomaviruses.- 2. Genomic Organization.- 3. Transcription.- 4. Replication.- 5. Transforming Functions.- 6. Viruses and Carcinogenic Progression.- Acknowledgement.- 7. References.- 19: Biological and Molecular Aspects of Simian Virus 40 (SV-40) and Polyomavirus Replication.- 1. General Overview.- A. Classification.- B. Isolation of Polyomaviruses.- C. The Permissive and Nonpermissive Virus/Cell Interactions.- D. SV40 and Polyoma Virions.- E. The Viral Minichromosome.- F. The Physical Maps of SV40 and Polyoma.- 2. The Lytic Cycle.- A. The SV40 Early Promoter.- B. The Products of the Early Region.- SV40.- Polyoma.- Polyoma Middle-T.- The Role of T Antigens.- C. The SV40 Late Promoter.- Attenuation.- D. Transcription Termination.- E. Processing of the Late RNA and Generation of the mRNAs.- SV40.- Polyoma.- F. Replication of SV-40 DNA and the Minimum Replication Origin.- T-Antigen and DNA Replication.- Termination of Replication.- G. Virus Assembly.- 3. Integration of Viral DNAs into the Cellular Genome.- Acknowledgements.- 4. References.- 20: The Molecular Biology of Adenoviruses.- A. Virion Structure.- B. Classification.- C. Questions under Study.- 1. The Molecular Biology of the Adenovirus Replication Cycle.- A. The Early Events in Viral Gene Expression.- B. The Late Events.- C. VA-RNA Translational Controls.- 2. The Molecular Biology of Adenovirus Transformation and Tumorigenesis.- 3. Conclusions.- 4. References.- 21: The Molecular Biology of Poxviruses.- 1. Classification.- 2. Basic Virion Structure.- A. DNA Genome.- B. Virion Polypeptides.- 3. The Infectious Cycle.- A. Virus Entry into Cells.- B. Early Transcription.- C. Late Transcription.- D. Host Factors in Virus Expression.- E. DNA Replication.- F. Virus Assembly and Release.- G. Cell Proliferation.- 4. Poxvirus Expression Vectors.- 5. Conclusions.- 6. References.- 22: Herpesviruses: biology, Gene Regulation, Latency, and Genetic Engineering.- 1. The Family Herpesviridae.- 2. The Herpes Virion and its Components.- A. Architecture, Composition, and Requirements for Infection.- B. The Polymorphism of Herpesvirus Genomes.- C. Micropolymorphism of Herpesvirus Genomes: An Epidemiologic Tool.- 3. Regulation of Gene Expression.- A. The General Pattern of Gene Expression.- B. Induction of Alpha Gene Expression by a Virion Structural Component.- C. A Specific Sequence Confers Inducibility upon Alpha Genes by Alpha-TIF.- D. Protein Binding Sites in Alpha Promoter-regulatory Domains.- E. The Regulation of Alpha Genes: A Microcosm of the General Pattern of Viral Gene Regulation.- F. Herpesvirus Genome Arrangement and Gene Structure..- G. The Synthesis of Herpesvirus DNAs.- H. Viral Replication and Cell Death.- 4.
Section I: Viruses at the Molecular Level.- 1: Viruses: An Overview.- 1. Historical Background.- 2. Viral Structure.- Helical Structure.- Icosahedrical Viruses.- Complex Viruses.- 3. Classification of Viruses.- 4. Viral Oncogenesis.- 5. Origin of Viruses.- 6. Viral Evolution.- 7. References.- 2: Viral Particles at Atomic Resolution.- 1. Virion Structure.- The Protein Component.- The "Canyon".- The Immunogenic Sites.- RNA-triggered Cleavage of VP2/VP4.- The Structure of Mengovirus.- Assembly.- The Canyon as Receptor Binding Site.- 2. Antiviral Drug Binding.- 3. Concluding Remarks.- Acknowledgements.- 4. References.- Section II: The Basic Processes Involved in Viral Replication.- 3: Strategy of Replication of the Viral Genome.- Viral One-Step Synchronized Growth Cycle.- 1. RNA Viruses.- A. Positive-strand RNA Viruses.- Picornavirus replication and the role of VPg.- Alphaviruses, Flaviviruses, Coronaviruses, and timing of (-) and (+) strand synthesis.- B. Negative-strand RNA Viruses.- Rhabdoviruses and Paramyxovirus.- Orthomyxoviruses and Bunyaviruses.- C. Reovirus and Double-stranded RNA Replication.- D. RNA Circles: Viroids, Virusoids and Plant Satellite Viruses.- E. RNA Replication: A Summary.- 2. DNA Viruses.- A. Simple Circles: Papova Viruses.- B. Modified Circular Replication: Rolling Circles and Concatamer Formation.- C. Concatamerization by Recombination: T-Phage and Iridoviruses.- D. Hairpin Structures and Viral Replication.- Parvovirus replication.- Poxvirus replication.- E. The Direct Approach: Protein Primers.- Adenovirus.- F. Viral Integration and Transposition.- Site-specific integration.- Integration at non-specific sites.- Integration at preferred sites.- Adenovirus integration.- Integration of Hepatitis B virus DNA.- Transposition and integration.- Bacteriophage Mu.- 3. Viruses that Use Reverse Transcriptase.- Hepadnaviruses.- Cauliflower Mosaic Virus.- 4. Concluding Remarks.- 5. References.- 4: Posttranscriptional Processing (Splicing and 3?-End Formation) of Nuclear Messenger RNA Precursors in Vitro.- General Outline.- A. Intermediates and Products of in vitro Pre-mRNA Splicing.- B. Comparison to Other Systems.- C. The Selection of Splice Sites in Self-splicing RNA: Cis-Alignment.- D. The Selection of Splice Sites in Nuclear Pre-mRNA: Trans-Alignment.- 1. 3?processing.- 2. Outlook.- 3. References.- 5: Regulation of Translation of Viral mRNAs.- 1. Strategies of Expression.- A. Group I: 1 AUG ? 1 Protein.- I-1. Multipartite genome.- I-2. Subgenomic RNAs.- I-3. Spliced mRNAs.- I-4. Ambisense RNAs.- B. Group II: 2 AUGs ? 2 Proteins.- II-1. Polycistronic mRNA.- II-2. Internal in-phase initiation within a gene.- II-3. Gene overlap in distinct reading frames.- C. Group III: 1 AUG ? 2 Proteins.- III-1. Readthrough or suppression of a termination codon.- III-2. Arrest of elongation independent of termination codons.- III-3. Frameshift during translation.- III-4. Post-translational cleavage.- 2. Regulation at the Level of Initiation.- A. Nature of the 5? Terminus of Viral RNAs and Role of this Terminus in Initiation Efficiency.- Structures encountered: Cap, VPg or ppX.- Cap structure and initiation efficiency.- Cap binding protein (CBP) and cap recognition.- Virus-induced shut-off based on cap recognition.- Secondary structure and length of leader.- Competition between viral mRNAs.- B. Choice of Initiator AUG.- Polycistronic viral mRNAs.- Bona fide polycistronic mRNAs.- mRNAs encoding "agnogenes".- Internal in-frame initiation within a gene.- Gene overlap in distinct reading frames.- C. Virus-encoded Regulation Factors.- RSV and its protein pl2.- Adenovirus and its VA RNAs.- 3. Regulation at the Level of Elongation and Termination.- A. Strategies of Regulation at the Level of Elongation and Termination among Plant and Animal Viral mRNAs: A Description.- Natural suppression.- Arrest of elongation independent of termination codons.- TYMV.- Alfalfa Mosaic Virus (AMV).- Encephalomyocarditis Virus (EMCV).- Frameshift during translation.- B. Molecular Bases of Translational Regulation at the Level of Elongation and Termination.- 4. Post-Translational Processing of Viral Polypeptides.- A. Definition and Overview of Virus Specific Proteolytic Processing.- Definition.- Overview of virus-specific proteolytic processing.- B. Proteolytic Processing in Various Virus Families.- Poliovirus and Cowpea Mosaic Virus.- Turnip Yellow Mosaic Virus.- Retroviruses.- C. Discussion.- Implications of the strategy of proteolytic processing.- Processing as a regulating step.- Cleavage and host-range pathogenicity.- Cleavage inhibitors and resistance to virus.- 5. Conclusions.- Acknowledgements.- 6. References.- Section III: Interference and Interferon.- 6: Biochemical Aspects of Interferon Action.- 1. IFN Receptors.- Receptors for g-IFN.- Binding Affinity.- 2. Interferon Induced Genes and Proteins.- A. IFN-induced Proteins.- The 56 kDa and Related Proteins.- Guanylate-binding Proteins.- Major Histocompatibility Antigens.- Metallothionein, Thymosin B4, and b-Thromoglobulin.- The Mx Gene.- IFN-induced Enzymatic Activities.- 3. dsRNA Dependent IFN-Induced Enzymatic Activities.- A. The Interferon-induced Protein Kinase Pathway.- B. The 2-5A Synthetase Pathway.- Enzymatic Components of the 2-5A System.- Genetics of the System.- Related Enzymic Activities.- The Multiple Forms of 2-5A Synthetases.- Biological Role of the 2-5A Pathway in the Antiviral Activities of IFN.- 4. Do We Understand the Biochemical Mechanisms of Antiviral Activity of IFN?.- Vaccinia virus.- Stable 2-5A oligonucleotide analogs.- DNA-dependent Kinase.- 5. Regulation of the Expression of the IFN-Induced Genes.- The Friedman-Stark Consensus Sequence.- 6. IFN, 2-5A and the Control of Cell Growth.- Acknowledgements.- 7. References.- 7: The Role of Defective Interfering (DI) Particles in Viral Infection.- Generation and Biology of DI.- Their Role in Infection.- DI Particles and Persistent Infection.- Acknowledgements.- References.- Section IV: The Strategies of Replication.- 8: Picornaviruses at the Molecular Level.- Overview.- Classification.- 1. The Virion.- A. The Protein Shell.- Topological relationships among structural proteins.- B. The RNA Component.- 2. The Replication Cycle.- A. Adsorption, Penetration and Uncoating.- B. Shut Off of Host Cell Synthesis.- C. Translation of Picornavirus RNA.- Initiation.- The extra-cistronic regions.- Two initiation sites.- Proteolytic processing.- D. Replication of Picornavirus RNA.- Viral replicase, VPg, and host factor.- 3. Genetic Recombination.- 4. Molecular Cloning.- A. Infectious cDNA.- Chimeras.- B. Conservation, Homology and Divergency.- 5. Open Questions.- 6. References.- 9: The Replication of Togaviridae and Flaviviridae at the Molecular Level.- 1. The Virion Structure.- A: Togaviridae.- B: Flaviviridae.- 2. Genomic Organization.- A: Togaviridae.- B. Flaviviridae.- 3. Virus Replication.- A. Togaviridae.- Virus Tropism.- Virus Uptake and Uncoating.- Translation of the Virion RNA.- Virus RNA Replication and Transcription.- Virus Structural Protein Formation.- Post Translational Events and Assembly of Virus.- B. Flaviviridae.- 4. Genetic Engineering of Togaviruses.- 5. Unsolved Problems.- 6. References.- 10: The Molecular Biology of Coronaviruses.- 1. Biological Properties.- 2. Coronavirus Structure: Genome RNA and Polypeptides.- A. The N Polypeptide.- B. The M Polypeptide.- C. The S Polypeptide.- D. Other Proteins.- 3. Replication.- A. Virus-specific RNA in Infected Cells.- B. Mechanism of RNA Synthesis.- C. Recombination.- D. Virus Assembly and Morphogenesis.- 4. Concluding Remarks.- Acknowledgements.- 5. References.- 11: Molecular Basis of Rhabdovirus Replication.- 1. The Virion.- 2. Genome Organization.- 3. Molecular Basis of Viral Replication.- A.