Main description:

the discovery of the "splicing" of the gene transcripts, the list would include the whole molecular genetics of the lambda bacteriophage, the notions of "promotor," "repressor," and "integration," the discovery of the reverse flow of genetic information, the very existence of oncogenes, the S'-terminal "cap" struc ture of eukaryotic mRNAs, ... Electronmicroscopy, ultracentrifugation and tissue culture were the landmarks on the way of the young science. During the past few years, however, a major (and not so silent) revolution took place: recombinant DNA technology with all its might entered in our laboratories, and restriction mapping of cloned genomes and sequencing gels have replaced plaque counting and sucrose gradients. The new techniques have made it possible to "dissect" the entire genome of a virus at the molecular level, and studies that would have been dreamt of just in the mid-seventies became the everyday experiments of our days. With new insight into the structure of viral genomes, and a deeper understanding of the mechanisms that regulate their expression, our view of viruses was bound to change: this volume bears witness to this impressive advance.

Contents:

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. 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. 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.