Basic Virology

MARTINEZ J. HEWLETT is Professor Emeritus in the Department of Molecular and Cellular Biology at the University of Arizona.

DAVID CAMERINI is Assistant Professor in the Department of Molecular Biology and Biochemistry at the University of California Irvine.

DAVID C. BLOOM is Associate Professor in the Department of Molecular Genetics and Microbiology at University of Florida.

Preface


Preface to the Second Edition


Preface to the Third Edition


Preface to the Fourth Edition


Acknowledgements


[PN]PART I


[PT]VIROLOGY AND VIRAL DISEASE


[PTOC]INTRODUCTION-THE IMPACT OF VIRUSES ON OUR VIEW OF LIFE


AN OUTLINE OF VIRUS REPLICATION AND VIRAL PATHOGENESIS


PATHOGENESIS OF VIRAL INFECTION


VIRUS DISEASE IN POPULATIONS AND INDIVIDUAL ANIMALS


VIRUSES IN POPULATIONS


ANIMAL MODELS TO STUDY VIRAL PATHOGENESIS


THE DYNAMICS OF VIRUS- HUMAN INTERACTIONS


PATTERNS OF SPECIFIC VIRAL DISEASES OF HUMANS


ADDITIONAL READING FOR PART I


PROBLEMS FOR PART I


[CN]CHAPTER 1


[CT]INTRODUCTION-THE IMPACT OF VIRUSES ON OUR VIEW OF LIFE


[CTOC] THE SCIENCE OF VIROLOGY


The effect of virus infections on the host organism and populations-viral pathogenesis, virulence, and epidemiology


The interaction between viruses and their hosts


The history of virology


Examples of the impact of viral disease on human history


Examples of the evolutionary impact of the virus-host interaction


The origin of viruses


Viruses have a constructive as well as destructive impact on society


Viruses are not the smallest self-replicating pathogens


QUESTIONS FOR CHAPTER 1


[CN]CHAPTER 2


[CT]AN OUTLINE OF VIRUS REPLICATION AND VIRAL PATHOGENESIS


[CTOC] VIRUS REPLICATION


Stages of virus replication in the cell


PATHOGENESIS OF VIRAL INFECTION


Stages of virus-induced pathology


Initial stages of infection-entry of the virus into the host


The incubation period and spread of virus through the host


Multiplication of virus to high levels-occurrence of disease symptoms


The later stages of infection-the immune response


The later stages of infection-virus spread to the next individual


The later stages of infection-fate of the host


QUESTIONS FOR CHAPTER 2


[CN]CHAPTER 3


[CT]VIRUS DISEASE IN POPULATIONS AND INDIVIDUAL ANIMALS


[CTOC] THE NATURE OF VIRUS RESERVOIRSSome viruses with human reservoirs


Some viruses with vertebrate reservoirs


VIRUSES IN POPULATIONS


Viral epidemiology in small and large populations


Factors affecting the control of viral disease in populations


ANIMAL MODELS TO STUDY VIRAL PATHOGENESIS


A mouse model for studying poxvirus infection and spread


Rabies: where is the virus during its long incubation period?


Herpes simplex virus latency


Murine models


Rabbit models


Guinea pig models


QUESTIONS FOR CHAPTER 3


[CN]CHAPTER 4


[CT]PATTERNS OF SOME VIRAL DISEASES OF HUMANS


[CTOC] THE DYNAMICS OF HUMAN-VIRUS INTERACTIONS


The stable association of viruses with their natural host places specific constraints on the nature of viral disease and mode of persistence


Classification of human disease-causing viruses according to virus-host dynamics


Viral diseases leading to persistence of the virus in the host are generally associated with viruses having long associations with human populations


Viral diseases associated with acute, severe infection are suggestive of zoonoses


PATTERNS OF SPECIFIC VIRAL DISEASES OF HUMANS


Acute infections followed by virus clearing


Colds and respiratory infections


Influenza


Variola


Infection of an "accidental" target tissue leading to permanent damage despite efficient clearing


Persistent viral infections


Papilloma and polyomavirus infections


Herpesvirus infections and latency


Other complications arising from persistent infections


Viral and subviral diseases with long incubation periods


Rabies


HIV-AIDS


Prion diseases


SOME VIRAL INFECTIONS TARGETING SPECIFIC ORGAN SYSTEMS


Viral infections of nerve tissue


Examples of viral encephalitis with grave prognosis


Rabies


Herpes encephalitis


Viral encephalitis with favorable prognosis for recovery


Viral infections of the liver (viral hepatitis)


Hepatitis A


Hepatitis B


Hepatitis C


Hepatitis D


Hepatitis E


QUESTIONS FOR CHAPTER 4


Part I Additional Reading


[PN]PART II


[PT]BASIC PROPERTIES OF VIRUSES AND VIRUS-CELL INTERACTION


[PTOC]VIRUS STRUCTURE AND CLASSIFICATION


CLASSIFICATION SCHEMES


THE VIROSPHERE


THE BEGINNING AND END OF THE VIRUS REPLICATION CYCLE


LATE EVENTS IN VIRAL INFECTION: CAPSID ASSEMBLY AND VIRION RELEASE


HOST IMMUNE RESPONSE TO VIRAL INFECTION


NATURE OF THE VERTEBRATE IMMUNE RESPONSE


LOCAL IMMUNITY


PRESENTATION OF ANTIGENS TO IMMUNE REACTIVE CELLS


CONTROL AND DYSFUNCTION OF IMMUNITY


MEASUREMENT OF THE IMMUNE REACTION


STRATEGIES TO PROTECT AGAINST AND COMBAT VIRAL INFECTION


VACCINATION-INDUCTION OF IMMUNITY TO PREVENT VIRUS INFECTION


EUKARYOTIC CELL-BASED DEFENSES AGAINST VIRAL REPLICATION


ANTIVIRAL DRUGS


BACTERIAL ANTIVIRAL SYSTEMS-RESTRICTION ENDONUCLEASES


ADDITIONAL READING FOR PART II


PROBLEMS FOR PART II


[CN]CHAPTER 5


[CT]VIRUS STRUCTURE AND CLASSIFICATION


[CTOC] THE FEATURES OF A VIRUS


Viral genomes


Viral capsids


Viral envelopes


CLASSIFICATION SCHEMES


The Baltimore scheme of virus classification


Disease-based classification schemes for viruses


THE VIROSPHERE


QUESTIONS FOR CHAPTER 5


[CN]CHAPTER 6


[CT]THE BEGINNING AND END OF THE VIRUS REPLICATION CYCLE


[CTOC] VIRAL ENTRY


Animal virus entry into cells-the role of the cellular receptor


Mechanisms of entry of nonenveloped viruses


Entry of enveloped viruses


Entry of virus into plant cells


Entry of virus into plant cells


Nonspecific methods of introducing viral genomes into cells


LATE EVENTS IN VIRAL INFECTION: CAPSID ASSEMBLY AND VIRION RELEASE


Assembly of helical capsids


Assembly of icosahedral capsids


Generation of the virion envelope and egress of the enveloped virion


QUESTIONS FOR CHAPTER 6


[CN]CHAPTER 7


[CT] THE INNATE IMMUNE RESPONSE: EARLY DEFENSE AGAINST PATHOGENS


HOST CELL-BASED DEFENSES AGAINST VIRUS REPLICATION


Toll-like receptors


Defensins


Interferon


Induction of interferon


The antiviral state


Measurement of interferon activity


Other cellular defenses against viral infection


Micro RNAs


THE ADAPTIVE IMMUNE RESPONSE AND THE LYMPHATIC SYSTEM


Two pathways of helper T response: the fork in the road


The immunological structure of a protein


Role of the antigen-presenting cell in initiation of the immune response


Clonal selection of immune reactive lymphocytes


Immune memory


Complement-mediated cell lysis


CONTROL AND DYSFUNCTION OF IMMUNITY


Specific viral responses to host immunity


Passive evasion of immunity-antigenic drift


Passive evasion of immunity-internal sanctuaries for infectious virus


Passive evasion of immunity-immune tolerance


Active evasion of immunity-immunosuppression


Active evasion of immunity-blockage of MHC antigen presentation


Consequences of immune suppression to virus infections


MEASUREMENT OF THE IMMUNE REACTION


Measurement of cell-mediated (T-cell) immunity


T-cell proliferation assay


Tetramer Assay


Measurement of antiviral antibody


Enzyme-linked immunosorbent assays (ELISAs)


Neutralization tests


Inhibition of hemagglutination


Complement fixation


QUESTIONS FOR CHAPTER 7


[CN]CHAPTER 8


[CT]STRATEGIES TO PROTECT AGAINST AND COMBAT VIRAL INFECTION


[CTOC]VACCINATION-INDUCTION OF IMMUNITY TO PREVENT VIRUS INFECTION


Antiviral vaccines


Smallpox and the history of vaccination


How a vaccine is produced


Live-virus vaccines


Killed-virus vaccines


Recombinant virus vaccines


Capsid and Subunit vaccines


DNA vaccines


Problems with vaccine production and use


EUKARYOTIC CELL-BASED DEFENSES AGAINST VIRUS REPLICATION


Other cellular defenses against viral infection


Small RNA-based defenses


Enzymatic modification of viral genomes


ANTIVIRAL DRUGS


Targeting antiviral drugs to specific features of the virus replication cycle


Other approaches


BACTERIAL ANTIVIRAL SYSTEMS-RESTRICTION ENDONUCLEASES


QUESTIONS FOR CHAPTER 8


[PN]PART III


[PT]WORKING WITH VIRUS


[PTOC]VISUALIZATION AND ENUMERATION OF VIRUS PARTICLES


REPLICATING AND MEASURING BIOLOGICAL ACTIVITY OF VIRUSES


THE OUTCOME OF VIRUS INFECTION IN CELLS


MEASUREMENT OF THE BIOLOGICAL ACTIVITY OF VIRUSES


PHYSICAL AND CHEMICAL MANIPULATION OF THE STRUCTURAL


COMPONENTS OF VIRUSES


VIRAL STRUCTURAL PROTEINS


CHARACTERIZING VIRAL GENOMES


CHARACTERIZATION OF VIRAL PRODUCTS EXPRESSED IN THE


INFECTED CELL


CHARACTERIZATION OF VIRAL PROTEINS IN THE INFECTED CELL


DETECTING AND CHARACTERIZING VIRAL NUCLEIC ACIDS


IN INFECTED CELLS


VIRUSES USE CELLULAR PROCESSES TO EXPRESS THEIR GENETIC


INFORMATION


THE MOLECULAR GENETICS OF VIRUSES


GENETIC MANIPULATION OF VIRAL GENOMES


DELIBERATE AND ACCIDENTAL ALTERATIONS IN VIRAL GENOMES


AS A RESULT OF LABORATORY REPLICATION


PROBLEMS FOR PART III


ADDITIONAL READING FOR PART III


[CN]CHAPTER 9


[CT]VISUALIZATION AND ENUMERATION OF VIRUS PARTICLES


[CTOC]Using the electron microscope to study and count viruses


Counting (enumeration) of virions in the electron microscope


Atomic Force Microscopy-a rapid and sensitive method for visualization of viruses and infected cells, potentially in real time.


Indirect methods for "counting" virus particles


QUESTIONS FOR CHAPTER 9


[CN]CHAPTER 10


[CT]REPLICATING AND MEASURING BIOLOGICAL ACTIVITY OF VIRUSES


[CTOC]Cell culture techniques


Maintenance of bacterial cells


Plant cell cultures


Culture of animal and human cells


Maintenance of cells in culture


Types of cells


Loss of contact inhibition of growth and immortalization of primary cells


THE OUTCOME OF VIRUS INFECTION IN CELLS


Fate of the virus


Fate of the cell following virus infection


Cell-mediated maintenance of the intra- and intercellular environment


Virus-mediated Cytopathology-changes in the physical appearance of cells


Virus-mediated Cytopathology-changes in the biochemical properties of cells


MEASUREMENT OF THE BIOLOGICAL ACTIVITY OF VIRUSES


Quantitative measure of infectious centers


Plaque assays


Generation of transformed cell foci


Use of virus titers to quantitatively control infection conditions


Examples of plaque assays


Statistical analysis of infection


Dilution endpoint methods


The relation between dilution endpoint and infectious units of virus


QUESTIONS FOR CHAPTER 10


[CN]CHAPTER 11


[CT]PHYSICAL AND CHEMICAL MANIPULATION OF THE STRUCTURAL COMPONENTS OF VIRUSES


[CTOC]VIRAL STRUCTURAL PROTEINS


Isolation of structural proteins of the virus


Size fractionation of viral structural proteins


Determining the stoichiometry of capsid proteins


The poliovirus capsid-a virion with equimolar capsid proteins


Analysis of viral capsids that do not contain equimolar numbers of proteins


CHARACTERIZING VIRAL GENOMES


Sequence analysis of viral genomes


Sanger sequencing


High-throughput sequencing (HTS)


Measuring the size of viral genomes


Direct measure of DNA genome lengths in the electron microscope


Rate zonal sedimentation and gel electrophoresis for measuring viral genome size


The polymerase chain reaction-detection and characterization of extremely small quantities of viral genomes or transcripts


QUESTIONS FOR CHAPTER 11


[CN]CHAPTER 12


[CT]CHARACTERIZATION OF VIRAL PRODUCTS EXPRESSED IN THE INFECTED CELL


[CTOC]CHARACTERIZATION OF VIRAL PROTEINS IN THE INFECTED


CELL


Pulse labeling of viral proteins at different times following infection


Use of immune reagents for study of viral proteins


Working with antibodies


The structure of antibody molecules


Monoclonal antibodies


Detection of viral proteins using immunofluorescence


Related methods for detecting antibodies bound to antigens


Use of bacterial staphylococcal A and streptococcal G proteins to detect


and isolate antibody-antigen complexes


Immunoaffinity chromatography


DETECTING AND CHARACTERIZING VIRAL NUCLEIC ACIDS IN


INFECTED CELLS


Detecting the synthesis of viral genomes


Characterization of viral mRNA expressed during infection


In situ hybridization


Further characterization of specific viral mRNA molecules


USE OF MICROARRAY TECHNOLOGY FOR GETTING A COMPLETE


PICTURE OF THE EVENTS OCCURRING IN THE INFECTED CELL


QUESTIONS FOR CHAPTER 12


[CN]CHAPTER 13


[CT]VIRUSES USE CELLULAR PROCESSES TO EXPRESS THEIR GENETIC INFORMATION


[CTOC] Prokaryotic DNA replication is an accurate enzymatic model for the process generally


The replication of eukaryotic DNA


The replication of viral DNA


The effect of virus infection on host DNA replication


Expression of mRNA


Prokaryotic transcription


Prokaryotic RNA polymerase


The prokaryotic promoter and the initiation of transcription


Control of prokaryotic initiation of transcription


Termination of transcription


Eukaryotic transcription


The promoter and initiation of transcription


Control of initiation of eukaryotic transcription


Processing of precursor mRNA


Posttranscriptional modification of precursor mRNA


Visualization and location of splices in eukaryotic transcripts


Post-transcriptional Regulation of eukaryotic mRNA function


Virus-induced changes in transcription and posttranscriptional processing


The mechanism of protein synthesis


Eukaryotic translation


Prokaryotic translation


Virus-induced changes in translation


QUESTIONS FOR CHAPTER 13


[PN]PART IV


[PT]REPLICATION PATTERNS OF SPECIFIC VIRUSES


[PTOC]REPLICATION OF POSITIVE-SENSE RNA VIRUSES


REPLICATION OF POSITIVE-SENSE RNA VIRUSES WHOSE GENOMES ARE TRANSLATED AS THE FIRST STEP IN GENE EXPRESSION


POSITIVE-SENSE RNA VIRUSES ENCODING A SINGLE LARGE OPEN READING FRAME


POSITIVE-SENSE RNA VIRUSES ENCODING MORE THAN ONE TRANSLATIONAL READING FRAME


REPLICATION OF PLANT VIRUSES WITH RNA GENOMES


REPLICATION OF BACTERIOPHAGE WITH RNA GENOMES


REPLICATION STRATEGIES OF RNA VIRUSES REQUIRING RNA-DIRECTED mRNA TRANSCRIPTION AS THE FIRST STEP IN VIRAL GENE EXPRESSION REPLICATION STRATEGIES OF SINGLE-STRANDED RNA


REPLICATION OF NEGATIVE-SENSE RNA VIRUSES WITH A MONOPARTITE GENOME


INFLUENZA VIRUSES-NEGATIVE-SENSE RNA VIRUSES WITH A MULTIPARTITE GENOME


OTHER NEGATIVE-SENSE RNA VIRUSES WITH MULTIPARTITE GENOMES


VIRUSES WITH DOUBLE-STRANDED RNA GENOMES


SUBVIRAL PATHOGENS


REPLICATION STRATEGIES OF SMALL AND MEDIUM-SIZED DNA VIRUSES


PAPOVAVIRUS REPLICATION


THE REPLICATION OF ADENOVIRUSES


REPLICATION OF SOME SINGLE-STRANDED DNA VIRUSES


REPLICATION OF SOME NUCLEAR REPLICATING EUKARYOTIC DNA VIRUSES WITH LARGE GENOMES


HERPESVIRUS REPLICATION AND LATENCY


BACULOVIRUS, AN INSECT VIRUS WITH IMPORTANT PRACTICAL USES IN MOLECULAR BIOLOGY


REPLICATION OF VIRUSES WITH DNA GENOMES THAT ENCODE THEIR OWN TRANSCRIPTION ENZYMES


POXVIRUSES-DNA VIRUSES THAT REPLICATE IN THE CYTOPLASM OF EUKARYOTIC CELLS


REPLICATION OF "LARGE" DNA-CONTAINING BACTERIOPHAGE


A GROUP OF ALGAL VIRUSES SHARES FEATURES OF ITS GENOME STRUCTURE WITH POXVIRUSES AND BACTERIOPHAGES


RETROVIRUSES: CONVERTING RNA TO DNA


RETROVIRUS FAMILIES AND THEIR STRATEGIES OF REPLICATION


MECHANISMS OF RETROVIRUS TRANSFORMATION


DESTRUCTION OF THE IMMUNE SYSTEM BY HIV


EUKARYOTIC CELLULAR GENETIC ELEMENTS RELATED TO RETROVIRUSES


HIV AND OTHER LENTIVIRUSES


HEPADNAVIRUSES: VARIATIONS ON THE RETROVIRUS THEME


DISCUSSION AND STUDY QUESTIONS FOR PART IV


ADDITIONAL READING FOR PART IV





[CN]CHAPTER 14


[CT]REPLICATION OF POSITIVE-SENSE RNA VIRUSES


[CTOC] RNA VIRUSES-GENERAL CONSIDERATIONS


A general picture of RNA-directed RNA replication


REPLICATION OF POSITIVE-SENSE RNA VIRUSES WHOSE GENOMES ARE TRANSLATED AS THE FIRST STEP IN GENE EXPRESSION


POSITIVE-SENSE RNA VIRUSES ENCODING A SINGLE LARGE OPEN READING FRAME


Picornavirus replication


The poliovirus genetic map and expression of poliovirus proteins


The poliovirus replication cycle


Picornavirus cytopathology and disease


Flavivirus replication


POSITIVE-SENSE RNA VIRUSES ENCODING MORE THAN ONE TRANSLATIONAL READING FRAME


Two viral mRNAs are produced in different amounts during togavirus infection


The viral genome


The virus replication cycle


Togavirus cytopathology and disease


A somewhat more complex scenario of multiple translational reading frames and subgenomic mRNA expression: coronavirus replication


Coronavirus replication


Cytopathology and disease caused by coronaviruses


REPLICATION OF PLANT VIRUSES WITH RNA GENOMES


Viruses with one genome segment


Viruses with two genome segments


Viruses with three genome segments


REPLICATION OF BACTERIOPHAGE WITH RNA GENOMES


Regulated translation of bacteriophage mRNA


[CS] Case Study


QUESTIONS FOR CHAPTER 14


[CN]CHAPTER15


[CT]REPLICATION STRATEGIES OF RNA VIRUSES REQUIRING RNA-DIRECTED mRNA TRANSCRIPTION AS THE FIRST STEP IN VIRAL GENE EXPRESSION


[CTOC] REPLICATION OF NEGATIVE-SENSE RNA VIRUSES WITH A MONOPARTITE GENOME


The replication of vesicular stomatitis virus-a model for Mononegavirales


The vesicular stomatitis virus virion and genome


Generation, capping, and polyadenylation of mRNA


The generation of new negative-sense virion RNA


The mechanism of host shutoff by vesicular stomatitis virus


The cytopathology and diseases caused by rhabdoviruses


Paramyxoviruses


The pathogenesis of paramyxoviruses


Filoviruses and their pathogenesis


Bornaviruses


INFLUENZA VIRUSES-NEGATIVE-SENSE RNA VIRUSES WITH A MULTIPARTITE GENOME


Involvement of the nucleus in flu virus replication


Generation of new flu nucleocapsids and maturation of the virus


Influenza A epidemics


OTHER NEGATIVE-SENSE RNA VIRUSES WITH MULTIPARTITE GENOMES


Orthobunyaviruses


Virus structure and replication


Pathogenesis


Arenaviruses


Virus gene expression


Pathogenesis


VIRUSES WITH DOUBLE-STRANDED RNA GENOMES


Orthoreovirus structure


The orthoreovirus replication cycle


Pathogenesis


SUBVIRAL PATHOGENS


Hepatitis delta virus


Viroids


Prions


[CS] Case Study


QUESTIONS FOR CHAPTER15


[CN]CHAPTER 16


[CT]REPLICATION STRATEGIES OF SMALL AND MEDIUM-SIZED DNA VIRUSES


[CTOC] DNA VIRUSES EXPRESS GENETIC INFORMATION AND REPLICATE THEIR GENOMES IN SIMILAR, YET DISTINCT, WAYS


PAPOVAVIRUS REPLICATION


Replication of SV40 virus-the model polyomavirus


The SV40 genome and genetic map


Productive infection by SV40


Abortive infection of cells nonpermissive for SV40 replication


The replication of papillomaviruses


The HPV-16 genome


Virus replication and cytopathology


THE REPLICATION OF ADENOVIRUSES


Physical properties of adenovirus


Capsid structure


The adenovirus genome


The adenovirus replication cycle


Early events


Adenovirus DNA replication


Late gene expression


VA transcription and cytopathology


Transformation of nonpermissive cells by adenovirus


REPLICATION OF SOME SINGLE-STRANDED DNA VIRUSES


Replication of parvoviruses


Dependovirus DNA integrates in a specific site in the host cell genome


Parvoviruses have potentially exploitable therapeutic applications


DNA viruses infecting vascular plants


Geminiviruses


The single-stranded DNA bacteriophage ?X174 packages its genes very compactly


[CS] Case Study


QUESTIONS FOR CHAPTER 16


[CN]CHAPTER 17


[CT]REPLICATION OF SOME NUCLEAR-REPLICATING EUKARYOTIC


DNA VIRUSES WITH LARGE GENOMES


[CTOC]HERPESVIRUS REPLICATION AND LATENCY


The herpesviruses as a group


Genetic complexity of herpesviruses


Common features of herpesvirus replication in the host


The replication of the prototypical alphaherpesvirus-HSV


The HSV virion


The viral genome


HSV productive infection


HSV latency and the LAT


HSV transcription during latency and reactivation


How do the LAT and other specific HSV genes function to accommodate reactivation?


EBV latent infection of lymphocytes, a different set of problems and answers


Pathology of herpesvirus infections


BACULOVIRUS, AN INSECT VIRUS WITH IMPORTANT PRACTICAL USES IN MOLECULAR BIOLOGY


Virion structure


Viral gene expression and genome replication


Pathogenesis


Importance of baculoviruses in biotechnology


[CS] Case Study


QUESTIONS FOR CHAPTER 17


[CN]CHAPTER 18


[CT]REPLICATION OF CYTOPLASMIC DNA VIRUSES AND "LARGE" BACTERIOPHAGES


[CTOC]POXVIRUSES-DNA VIRUSES THAT REPLICATE IN THE CYTOPLASM OF EUKARYOTIC CELLS


The pox virion is complex and contains virus-coded transcription enzymes


The poxvirus replication cycle


Early gene expression


Genome replication


Intermediate and late stages of replication


Pathogenesis and history of poxvirus infections


Is smallpox virus a potential biological terror weapon?


REPLICATION OF "LARGE" DNA-CONTAINING BACTERIOPHAGES


Components of large DNA-containing phage virions


Replication of phage T7


The genome


Phage-controlled transcription


The practical value of T7


T4 bacteriophage: the basic model for all DNA viruses


The T4 genome


Regulated gene expression during T4 replication


Capsid maturation and release


Replication of phage ?-- a "simple" model for latency and reactivation


The phage ? genome


Phage ? gene expression immediately after infection


Biochemistry of the decision between lytic and lysogenic infection in E. coli


Factors affecting the lytic/lysogenic "decision"


A GROUP OF ALGAL VIRUSES SHARES FEATURES OF ITS GENOME STRUCTURE WITH POXVIRUSES AND BACTERIOPHAGES


QUESTIONS FOR CHAPTER 18


[CN]CHAPTER 19


[CT]RETROVIRUSES: CONVERTING RNA TO DNA


[CTOC]RETROVIRUS FAMILIES AND THEIR STRATEGIES OF REPLICATION


The molecular biology of retrovirus replication


Replication of retroviruses: an outline of the replication process


Initiation of infection


Capsid assembly and maturation


Action of reverse transcriptase and RNase H in synthesis of cDNA


Integration of the retroviral cDNA into the host genome


Transcription and translation of viral mRNA


Capsid assembly and morphogenesis


MECHANISMS OF RETROVIRUS TRANSFORMATION


Transformation through the action of a viral oncogene-a subverted cellular growth control gene


Oncornavirus alteration of normal cellular transcriptional control of growth regulation


Oncornavirus transformation by growth stimulation of neighboring cells


CELLULAR GENETIC ELEMENTS RELATED TO RETROVIRUSES


Retrotransposons


The relationship between transposable elements and viruses


QUESTIONS FOR CHAPTER 19


[CN]Chapter 20


[CT]HUMAN IMMUNODEFICIENCY VIRUS TYPE 1 (HIV-1) AND RELATED LENTIVIRUSES


[CTOC] HIV-1 and related lentiviruses


The origin of HIV-1 and AIDS


HIV-1 and lentiviral replication


Destruction of the immune system by HIV-1


[CS] Case Study


[CN]CHAPTER 21


[CT]HEPADNAVIRUSES: VARIATIONS ON THE RETROVIRUS THEME


[CTOC]The virion and the viral genome


The viral replication cycle


The pathogenesis of hepatitis B virus


Prevention and treatment of hepatitis B virus infection


Hepatitis D virus


A plant "hepadnavirus": cauliflower mosaic virus


The evolutionary origin of hepadnaviruses


[CS] Case Study


QUESTIONS FOR CHAPTER 21


[PN]PART V:


[PT]MOLECULAR GENETICS OF VIRUSES


[PT]MOLECULAR PATHOGENESIS


[PT]VIRAL BIOINFORMATICS AND BEYOND


[PT]VIRUSES AND THE FUTURE: PROBLEMS AND PROMISES


DISCUSSION AND STUDY QUESTIONS FOR PART V


ADDITIONAL READING FOR PART V


[CN]CHAPTER 22


[CT]THE MOLECULAR GENETICS OF VIRUSES


[CTOC]Mutations in genes and resulting changes to proteins


Analysis of Mutations


Complementation


Recombination


Isolation of mutants


Selection


HSV thymidine kinase-a portable selectable marker


Screening


A TOOL KIT FOR MOLECULAR VIROLOGISTS


Viral genomes


Locating sites of restriction endonuclease cleavage on the viral genome-restriction mapping


Cloning Vectors


Cloning of fragments of viral genomes using bacterial plasmids/


Cloning using phage l


Cloning single stranded DNA with bacteriophage M13


DNA animal virus vectors


RNA virus expression systems


Defective virus particles


Mutagenesis of viral genes


Site directed mutagenesis


Generation of recombinant viruses


Bacterial artificial chromosomes


CRISPR-Cas


QUESTIONS FOR CHAPTER 22


[CN]CHAPTER 23


[CT]MOLECULAR PATHOGENESIS


[CTOC] AN INTRODUCTION TO THE STUDY OF VIRAL PATHOGENESIS


ANIMAL MODELS


Choosing a model: natural host vs. surrogate models


Development of new models: transgenic animals


Hybrid models: the SCID-hu mouse


Considerations regarding the humane use of animals


METHODS FOR THE STUDY OF PATHOGENESIS


Assays of virulence


Analysis of viral spread within the host


Resolving the infection to the level of single cells.


CHARCTERIZATION OF THE HOST RESPONSE


Immunological Assays


Use of transgenic mice to dissect critical components of the host immune response that modulate the viral infection


QUESTIONS FOR CHAPTER 23


[CN]Chapter 24


[CT]Viral Bioinformatics


[CTOC] Bioinformatics


Biological Databases


Biological Applications


Systems Biology and Viruses


Viral Internet Resources


Questions for Chapter 24


[CN]CHAPTER 25


[CT]VIRUSES AND THE FUTURE-PROBLEMS AND PROMISES


[CTOC]Clouds on the horizon-emerging disease


What are the prospects of using medical technology to eliminate specific viral and other infectious diseases?


Silver linings-viruses as therapeutic agents, viruses as technological tools, the place of viruses in the biosphere.


Why study virology?


QUESTIONS FOR CHAPTER 25


Appendix


Resource Center


Technical Glossary


Index