BRIEF CONTENTS SECTION I: INTRODUCTION 11. Picornaviruses 125 TO VIROLOGY Bert L. Semler, University of California, Irvine 1 2. Flaviviruses 137 1. Introduction to Virology 2 Richard Kuhn, Purdue University Nicholas H. Acheson, McGill University 1 3. Togaviruses 148 2. Virus Structure and Assembly 18 Milton Schlesinger, Washington University Stephen C. Harrison, Harvard University in St. Louis Sondra Schlesinger, Washington University 3. Virus Classification: The World in St. Louis of Viruses 31 Revised by: Richard Kuhn, Purdue University Nicholas H. Acheson, McGill University 1 4. Coronaviruses 159 4. Virus Entry 45 Mark Denison, Vanderbilt University Ari Helenius, Swiss Federal Institute of Michelle M. Becker, Vanderbilt University Technology, Zurich SECTION II: VIRUSES OF SECTION IV: NEGATIVE-STRAND BACTERIA AND ARCHAEA AND DOUBLE-STRANDED RNA VIRUSES OF EUKARYOTES 5. Single-Stranded RNA Bacteriophages 59 1 5. Paramyxoviruses and Rhabdoviruses 175 Jan van Duin, University of Leiden Nicholas H. Acheson, McGill University 6. Microviruses 69 Daniel Kolakofsky, University of Geneva Christopher Richardson, Dalhousie University Bentley Fane, University of Arizona Revised by: Laurent Roux, University of Geneva 7. Bacteriophage T7 77 1 6. Filoviruses 188 William C. Summers, Yale University Heinz Feldmann, Division of Intramural Research, MAID, NIH 8. Bacteriophage Lambda 85 Hans-Dieter Klenk, University of Marburg Michael Feiss, University of Iowa Nicholas H. Acheson, McGill University 9. Viruses of Archaea 97 17. Bunyaviruses 200 David Prangishvili, Institut Pasteur Richard M. Elliott, University of St. Andrews SECTION III: POSITIVE-STRAND 1 8. Influenza Viruses 210 RNA VIRUSES OF EUKARYOTES DaliusJ. Briedis, McGill University 1 O. Cucumber Mosaic Virus 112 1 9. Reoviruses 225 Ping XΜ, J. Noble Research Institute Terence S. Dermody, Vanderbilt University Marilyn J. Roosinck, J. Noble Research Institute James D. Chappell, Vanderbilt University VI Brief Contents SECTION V: SMALL DNA VIRUSES 29. Human Immunodeficiency OF EUKARYOTES Virus 354 Alan Cochrane, University of Toronto 20. Parvoviruses 238 Peter Beard, Swiss Institute for Experimental 30. Hepadnaviruses 365 Cancer Research Christopher Richardson, Dalhousie University 21. Polyomaviruses 247 SECTION VIII: VIROIDS Nicholas H. Acheson, McGill University AND PRIONS 22. Papillomaviruses 263 31. Viroids and Hepatitis Greg Matlashewski, McGill University Delta Virus 378 Revised by: Lawrence Banks, International Jean-Pierre Perreault, Universite de Sherbrooke Centre for Genetic Engineering and Martin Pelchat, University of Ottawa Biotechnology, Trieste 32. Prions 387 DaliusJ. Briedis, McGill University SECTION VI: LARGER DNA VIRUSES OF EUKARYOTES SECTION IX: HOST DEFENSES 23. Adenoviruses 274 AGAINST VIRUS INFECTION Philip Branton, McGill University Richard C. Marcellus, McGill University 33. Intrinsic Cellular Defenses Against Virus Infection 398 24. Herpesviruses 285 Karen Mossman, McMaster University Pierre Genin, University Paris Descartes Bernard Roizman, University of Chicago John Hiscott, McGill University Gabriella Campadelli-Fiume, University of Bologna Richard Longnecker, Northwestern University 34. Innate and Adaptive Immune Responses to Virus Infection 415 25. Baculoviruses 302 Malcolm G. Baines, McGill University Eric B. Carstens, Queen s University Karen Mossman, McMaster University 26. Poxviruses 312 Richard C. Condit, University of Florida SECTION X: ANTIVIRAL AGENTS AND VIRUS VECTORS 27. Viruses of Algae and 35. Antiviral Vaccines 428 Mimi virus 325 Brian Ward, McGill University Michael J. Allen, Plymouth Marine Laboratory William H. Wilson, Bigeloro Laboratory for Ocean Sciences 36. Antiviral Chemotherapy 444 Donald M. Coen, Harvard University SECTION VII: VIRUSES THAT USE 37. Eukaryotic Virus Vectors 456 A REVERSE TRANSCRIPTASE Renald Gilbert, NRC Biotechnology Research Institute, Montreal 28. Retroviruses 342 Bernard Massie, NRC Biotechnology Research Institute, Alan Cochrane, University of Toronto Montreal CONTENTS SECTION I: INTRODUCTION Analysis of viral macromolecules reveals the detailed TO VIROLOGY pathways of virus replication 13 STEPS IN THE VIRUS 1. Introduction to Virology 2 REPLICATION CYCLE 13 1. Virions bind to receptors on the cell surface 13 THE NATURE OF VIRUSES 3 2. The virion (or the viral genome) enters the cell 14 Viruses consist of a nucleic acid genome packaged in a 3. Early viral genes are expressed: the Baltimore protein coat 3 classification of viruses 14 Viruses are dependent on living cells for their replication The seven groups in the Baltimore classification system 14 Virus particles break down and release their 4. Early viral proteins direct replication of viral genomes 15 genomes inside the cell 3 5. Late messenger RNAs are made from newly Virus genomes are either RNA or DNA, but not both 4 replicated genomes 15 WHY STUDY VIRUSES? 4 6. Late viral proteins package viral genomes and Viruses are important disease-causing agents 4 assemble virions 16 Viruses can infect all forms of life 4 7. Progeny virions are released from the host cell 16 Viruses are the most abundant form of life on Earth 5 The study of viruses has led to numerous discoveries in 2. Virus Structure and Assembly 18 molecular and cell biology 5 BASIC CONCEPTS OF VIRUS A BRIEF HISTORY OF VIROLOGY: STRUCTURE 18 TH E STU DY OF VI RUSES 6 Virus structure is studied by electron microscopy The scientific study of viruses is very recent 6 and X-ray diffraction 19 Viruses were first distinguished from other Many viruses come in simple, symmetrical packages 19 microorganisms by filtration 6 The crystallization of tobacco mosaic virus challenged CAPSIDS WITH ICOSAHEDRAL conventional notions about genes and the nature SYMMETRY 21 of living organisms 6 Some examples of virions with icosahedral symmetry The "phage group" stimulated studies of bacteriophages The concept of quasi-equivalence 21 and helped establish the field of molecular biology 7 Larger viruses come in more complex packages 2 3 Study of tumor viruses led to discoveries in molecular CAPSIDS WITH HELICAL SYMMETRY 25 biology and understanding of the nature of cancer 8 VIRAL ENVELOPES 26 DETECTION AND TITRATION OF VIRUSES Viral envelopes are made from lipid bilayer membranes 26 Most viruses were first detected and studied by Viral glycoproteins are inserted into the lipid infection of intact organisms 9 membrane to form the envelope 2 7 The plaque assay arose from work with bacteriophages 9 Eukaryotic cells cultured in vitro have been adapted PACKAGING OF GENOMES AND VIRION for plaque assays 9 ASSEMBLY 28 Hemagglutination is a convenient and rapid assay Multiple modes of capsid assembly 2 8 for many viruses 10 Specific packaging signals direct incorporation of Virus particles can be seen and counted by electron viral genomes into virions 2 8 microscopy 10 Core proteins may accompany the viral genome The ratio of physical virus particles to infectious inside the capsid 28 particles can be much greater than 1 11 Formation of viral envelopes by budding is driven by interactions between viral proteins 2 8 THE VIRUS REPLICATION CYCLE: AN OVERVIEW 11 DISASSEMBLY OF VIRIONS: THE DELIVERY The single-cycle virus replication experiment 11 OF VIRAL GENOMES TO THE HOST CELL 29 An example of a virus replication cycle: mouse Virions are primed to enter cells and release polyomavirus 12 their genome 29 VII VIII Contents 3. Virus Classification: The World A variety of cell surface proteins can serve as specific virus of Viruses 31 receptors 47 Receptors interact with viral glycoproteins, surface VIRUS CLASSIFICATION 31 protrusions, or "canyons" on the surface of the virion 48 Many different viruses infecting a wide variety Many viruses enter the cell via receptor-mediated of organisms have been discovered 31 endocytosis 48 Virus classification is based on molecular architecture, Passage from endosomes to the cytosol is often triggered by genetic relatedness, and host organism 3 1 low pH 49 Viruses are grouped into species, genera, and families 32 Membrane fusion is mediated by specific viral "fusion Distinct naming conventions and classification schemes proteins" 50 have developed in different domains of virology 33 Fusion proteins undergo major conformational changes MAJOR VIRUS GROUPS 33 that lead to membrane fusion 50 Study of the major groups of viruses leads to Non-enveloped viruses penetrate by membrane lysis or understanding of shared characteristics pore formation 51 and replication pathways 3 3 Virions and capsids are transported within the cell in Viruses with single-stranded DNA genomes are small and vesicles or on microtubules 52 have few genes 34 Import of viral genomes into the nucleus 52 Viruses with double-stranded DNA genomes include the The many ways in which viral genomes are largest known viruses 3 5 uncoated and released 54 Most plant viruses and many viruses of vertebrates have positive-strand RNA genomes 35 SECTION II: VIRUSES OF Viruses with negative-strand RNA genomes have helical BACTERIA AND ARCHAEA nucleocapsids; some have fragmented genomes 38 Viruses with double-stranded RNA genomes have fragmented genomes and capsids with icosahedral 5. Single-Stranded RNA symmetry 3 8 Bacteriophages 59 Viruses with a reverse transcription step in their replication The discovery of RNA phages stimulated cycle can have either RNA or DNA genomes 39 research into messenger RNA function and Satellite viruses and satellite nucleic acids require a helper RNA replication 59 virus to replicate 40 RNA phages are among the