The third volume in the Institute of Animal Health (IAH) Biology of Animal Infections Series, Bluetongue discusses one of the most economically important diseases of domesticated livestock. Affecting primarily sheep particularly the improved mutton and wool breeds, it is now endemic in Africa, India, the Middle and Far East, Australia and the Americas, and over the last six years has caused a series of outbreaks throughout the Mediterranean region and central Europe. Bluetongue represent a paradigm not only for the other orbiviruses (such as African horse sickness virus, which shares the same vector species) but also for other insect transmitted diseases, including those of humans.
* The only single definitive work that provides both historical and up to date data on the disease
* Describes the latest developments in epidemiological modelling, molecular epidemiology and vaccine development, as well as explaining the current global epidemiology of the disease
* Outlines the importance and possible mechanisms of overwintering, and the impact of global warming on the vectors and virus distribution

SARS was the ?rst new plague of the twenty-?rst century. Within months, it spread worldwide from its "birthplace" in Guangdong Province, China, affecting over 8,000 people in 25 countries and territories across ?ve continents. SARS exposed the vulnerability of our modern globalised world to the spread of a new emerging infection. SARS (or a similar new emerging disease) could neither have spread so rapidly nor had such a great global impact even 50 years ago, and arguably, it was itself a product of our global inter-connectedness. Increasing af?uence and a demand for wild-game as exotic food led to the development of large trade of live animal and game animal markets where many species of wild and domestic animals were co-housed, providing the ideal opportunities for inter-species tra- mission of viruses and other microbes. Once such a virus jumped species and attacked humans, the increased human mobility allowed the virus the opportunity for rapid spread. An infected patient from Guangdong who stayed for one day at a hotel in Hong Kong led to the transmission of the disease to 16 other guests who travelled on to seed outbreaks of the disease in Toronto, Singapore, and Vietnam, as well as within Hong Kong itself. The virus exploited the practices used in modern intensive care of patients with severe respiratory disease and the weakness in infection control practices within our health care systems to cause outbreaks within hospitals, further amplifying the spread of the disease. Health-care itself has become a two-edged sword.

Published since 1953, Advances in Virus Research covers a diverse range of in-depth reviews providing a valuable overview of the current field of virology.
In 2004, the Institute for Scientific Information released figures showing that the series has an Impact Factor of 2.576, with a half-life of 7.1 years, placing it 11th in the highly competitive category of Virology.

Until late 1960s the coronaviruses were not recognized as pathogens responsible for human diseases (common cold), and it has been in 2003 when human coronaviruses (HCoVs) recalled worldwide attention with the emergence of the severe and acute respiratory syndrome (SARS), produced by a coronavirus (SARS-CoV) that has infected more than 8000 people, killing about ten percent of them in 32 countries. The increase of research on coronaviruses has soon lead to the discovery of another human coronavirus (HCoV-NL63) which is prevalent in 7% of hospital patients and has been associated with bronchiolitis and, possibly, conjunctivitis.

Retroviruses have been of great importance to biomedical science for the past half century. Initially, studies on oncogenic animal retroviruses provided important insights into molecular processes in carcinogenesis – most notably the existence and mechanisms of action of oncogenes and proto-oncogenes. Moreover, several human diseases are caused by retroviruses, including AIDS, adult T-cell leukemia and the neurological disease HAM/TSP. The topic of this volume is a relatively unknown animal retrovirus, jaagsiekte sheep retrovirus, the causative agent of transmissible lung cancer in sheep –ovine pulmonary adenocarcinoma. The disease was first documented in South Africa in the 1800s, it has a wide geographical distribution, and it is of economic importance in high endemic regions. However, until very recently the nature of the etiologic agent was unclear, and relatively few laboratories actively studied the disease.

Over 50% of known flaviviruses have been associated with human disease. The "Flavivirus" genus constitutes some of the most serious human pathogens including Japanese encephalitis, dengue and yellow fever. Flaviviruses are known for their complex life cycles and epidemic spread, and are considered a globally-emergent viral threat.
Detection, Diagnosis and Vaccine Development, the third volume of The Flaviviruses details the current status of technologies for detection and differentiation of these viruses, their use in surveillance and outbreak investigation, and also reviews the latest clinical research.
* Comprehensive approach to the scientific disciplines needed to unravle the complexities of virus-host interactions
* Descibes the technologies that have contributed to our current knowledge about the Flaviviruses
* Identifies the major problems faced in understanding the virus-host interactins that result in disease
* An exhaustive compendium of current and past knowledge on the Flavivirus family

This volume covers the full spectrum of modern structural virology. Its goal is to describe the means for defining moderate to high resolution structures and the basic principles that have emerged from these studies. Among the topics covered are Hybrid Vigor, Structural Folds of Viral Proteins, Virus Particle Dynamics, Viral Gemone Organization, Enveloped Viruses and Large Viruses.
* Covers viral assembly using heterologous expression systems and cell extracts
* Discusses molecular mechanisms in bacteriophage T7 procapsid assembly, maturation and DNA containment
* Includes information on structural studies on antibody/virus complexes

The third edition of this volume expands upon the previous two editions with new and up-to-date methods and protocols. Chapters include step-by-step procedures involved in quantifying cell growth, baculovirus infection and cell metabolism, methods to isolate new cell lines and develop your own serum-free medium, and routine maintenance and storage of insect cell lines and baculoviruses, small- and large-scale recombinant protein production with the BEVS in both insect and mammalian cell culture and in insect larvae, production and characterization of baculoviruses, green fluorescent protein, tubular reactors and RNAi, and baculovirus/insect cell system to study apoptosis and generating envelop-modified baculovirus for gene delivery into mammalian cells. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and key tips on troubleshooting and avoiding known pitfalls. Authoritative and practical, Baculovirus and Insect Cell Expression Protocols, Third Edition aims to not only aid the user in successfully completing the tasks described, but also stimulate the development of improved techniques and new applications of baculoviruses and insect cell culture.

For a virus to invade a host cell it needs to penetrate the physical barrier imposed by the plasma membrane. Viruses have evolved specialized surface proteins to meet this challenge. These proteins facilitate delivery of the viral genetic information into the host cell by either fusing the viral envelope with a host cell membrane or by forming membrane pores. Membrane fusion and pore formation critically depend on the engagement of host cell receptors and receptor choice is a key determinant of viral tropism. The multi-faceted interplay between viral and cellular factors during virus entry is a fascinating field of study, which can provide important insight into viral pathogenesis and define new targets for intervention. This book provides a comprehensive overview of this exciting field of research.

One hundred years ago, when Martinus W. Beijerinck in Delft and Friedrich Loeffler on Riems Island discovered a new class of infectious agents in plants and animals, a new discipline was born. This book, a compilation of papers written by well-recognized scientists, gives an impression of the early days, the pioneer period and the current state of virology. Recent developments and future perspectives of this discipline are sketched against a historic background. With contributions by A. Alcami, D. Baulcombe, F. Brown, L. W. Enquist, H. Feldmann, A. Garcia-Sastre, D. Griffiths, M. C. Horzinek, A. van Kammen, H.-D. Klenk, F. A. Murphy, T. Muster, R. O'Neill, P. Palese, C. Patience, R. Rott, H.- P. Schmiedebach, S. Schneider-Schaulies, G. L. Smith, J. A. Symons, Y. Takeuchi, V. ter Meulen, P. J. W. Venables, V. E. Volchkov, V. A. Volchkova, R. A. Weiss, W. Wittmann, H. Zheng

Advances in Applied Microbiology, Volume 119 continues the comprehensive reach of this widely read and authoritative review source in microbiology. Users will find invaluable references and information on a variety of areas relating to the topics of microbiology.

Plant Virology Protocols: New Approaches to Detect Viruses and Host Responses addresses recent developments in genome analyses and cytological technologies being used today to learn more about plant virology. Opening with chapters covering techniques relevant to the detection of unknown viruses and disease diagnosis, this detailed volume continues with chapters on the utilization of meta-genome sequencing and global gene expression analyses for the search and identification of viruses, as well as the elucidation of host responses to viral infection, construction methods of infectious cDNAs, and methods relevant to plant virus control. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and practical, Plant Virology Protocols: New Approaches to Detect Viruses and Host Responses will be an invaluable guide to researchers working in the field of plant sciences.

Although there have been many books on HIV and AIDS, surprisingly little has been published that focuses on the immunology of retroviral infections in general, and HIV in particular. Retroviral Immunology: Immune Response and Restoration is the first book of its kind to address the most important aspects of the immunology of retroviruses, including not only the virus-specific immune responses, but also genetic and virologic factors modulating these responses. The book also deals directly with the emerging concept of immune restora tion in retroviral infections, a particularly important subject to the thousands of clinicians who deal with this problem on a daily basis. With the advent of highly effective antiviral drug regimens to slow down the replication of HIV and the progression of AIDS, new challenges and opportunities are arising. Restoration of general immune function has brought with it not only complica tions of immune restoration-mediated disease, but also the realistic hope for meaningful restoration of the ability to control HIV replication with the immune system. Leading scientists in the field have summarized the most current informa tion regarding experimental and clinical aspects of retroviral infections. Retroviral Immunology: Immune Response and Restoration should prove an impor tant point of reference for basic scientists and clinicians in this area of research. We are indebted to all of our authors for their excellent contributions."

Recombinant viruses provide an efficient mechanism for the transfer and expression of DNA in eukaryotic cells. First, the transfer of DNA by viral infection-utilizing specific cell surface receptors and cellular intern- ization mechanisms-occurs much more readily than DNA transfer via uptake induced by such physical methods as calcium phosphate coprecipitation or electroporation. Second, the novel strategies employed by the virus to express its own genes can then be "hijacked" in the recombinant virus to express the researcher's gene of interest The purpose of Practical Molecular Virology isthus to compile a coll- tion of readily repeatable gene transfer and expression methods from wo- ers expert in the use of a variety of recombinant viral vectors . These include those designed for the production of recombinant antigens, such as pol- virus and yeast Ty-VLPs; those giving very high levels of recombinant protein expression, for example, baculovirus, vaccinia virus, and SV40; and finally viral vectors used for efficient, stable gene transfer to eu otic cells, such as retroviruses and herpesviruses . The first chapter describes the viral life cycle for each virus, and explains how this can be adapted to allow construction of recombinant vectors. Subsequent chapters deal with methods for producing and char- terizing recombinant viruses . I make no apology for the hyperproliferation of chapters dealing with recombinant retroviral methods and applications, since I believe this is clearly proportional to the recent expansion of interest in these techniques.

Structure-Function Relationships of Human Pathogenic Viruses provides information on the mechanisms by which viruses enter the cell, replicate, package their DNA into capsids and mature into new virions. The relation between structural features and the pathogenicity and oncogenicity of some of the most relevant human viral pathogens are demonstrated and the acquisition of defense mechanisms through virus-host interactions are presented. In contrast to textbooks, this volume combines timely research data to provide a holistic view of viral pathogenesis.

Furthermore Structure-Function Relationships of Human Pathogenic Viruses illustrates in a single volume the fundamental processes involved in viral life cycles using up-to-date information from research laboratories around the world. Knowledge of these processes is crucial to develop rationales for the design of future drugs. The timeliness of the data and the comprehensive yet concise approach this book takes in order to present the world of viral pathogens should make it a frontrunner in higher education and R&D.

Negative-strand RNA viruses, so named because of the polarity of their genomic RNA to mRNA, include important human and non-human pathogens. This volume covers major advances in reverse genetics techniques over the past decade, state-of-the-art basic science and the clinical implications of experimental findings. This should rekindle interest in negative-strand RNA viruses among readers, including those in other disciplines, leading to further progress in understanding these important viruses and in developing effective measures of control.

Viruses and RNAi share an intricate relationship at many levels. RNAi is an important antiviral defense mechanism in plants and invertebrates, microRNAs of viral or cellular origin affect many aspects of virus biology, and replication of many, if not all, mammalian viruses can be suppressed by RNAi." Antiviral RNAi: Concepts, Methods, and Applications "provides a collection of protocols for the analysis of viral small RNAs and natural antiviral RNAi responses as well as for the development and optimization of RNAi-based antiviral drugs. As RNAi is a central regulatory mechanism in the cell, the methods in this volume can also be applied out of the context of a virus infection. Divided into five convenient parts, this detailed volume reviews important basic concepts in the field of antiviral RNAi, provides experimental and bio-informatic tools for the analysis of small silencing RNAs, covers methods to biochemically dissect RNAi-based antiviral defense and viral counter-defense mechanisms, describes methods for the design, expression, and delivery of therapeutic antiviral siRNAs, and finally presents genome-wide RNAi approaches for the identification of factors involved in virus replication. Written in the highly successful "Methods in Molecular Biology " series format, chapters contain introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and notes on troubleshooting and avoiding known pitfalls.

Authoritative and accessible, "Antiviral RNAi: Concepts, Methods, and Applications" serves as an ideal guide for both novice and experienced researchers alike striving to dissect the role of RNAi in the viral life cycle or to further boost the development of novel therapeutics and experimental tools based on RNAi technology.

After three volumes on adenoviruses in 1995 the past years have seen rapid progress in the field of adenovirus research. Moreover, adenoviruses have attracted considerable interest as vectors in gene transfer regimens. After the first volume on virion and structure, viral replication and host-cell interaction this second volume deals with the immune system, oncogenesis and gene therapy.

The history of research on hog cholera (HC)/classical swine fever (CSF) can be roughly divided into three phases which are characterized by the methods available at the time for demonstrati ng the causati ve agent. Phase covered the period before the viral etiology of HC was discovered by de Schweinitz and Dorset (1904)*. Thereafter (Phase II) the detection of HC virus (HCV) was accomplished by laborious, time-consuming and costly pig inoculation experiments. This explains the extensive search for methods not only for detection but also for accurate infectivity titration as well as for applicable serological techniques to solve urgent problems concerning the pathogenesis, diagnosis, epidemiology and prophylaxis of HC. It was not before the late fifties that HC research entered Phase III when fluorescent antibody techniques offered not only the means for detection and titration of HCV in porcine cell cultures but also for more intensive research on hog cholera and its virus. And yet, there are a number of questions to be answered, e. g. on the genetic and antigenic relation of HCV to bovine viral diarrhea (BVD) virus. There are indications that Phase IV of HC research will bear the stamp of biotechnology. In view of this development it appears appropriate to give an up-dating and summarizing account of HC/CSF including comparative aspects of infections caused by structurally related viruses. The editIon of the present volume would have been impossible without the cooperation of several known scientists who instantly agreed when asked for contribution.

The articles in this volume provide a comprehensive overview of our current understanding of the roles played by cellular factors in the early steps of retroviral replication. A better understanding of these functions will provide critical new insights into retrovirus-host cell interactions and is likely to prove useful for the future development of effective antiretroviral therapies.

Hepatobiliary cancer refers to primary malignant tumors originating in cells of the liver, bile ducts, and gallbladder. Globally, primary liver cancer, which includes hepatocellular carcinoma (~75 % of all cases) and intrahepatic biliary cancer or cholangiocarcinoma (~10-15 % 0f all cases) is the 6th most commonly diagnosed cancer and 3rd leading cause of cancer deaths worldwide. The vast majority of these highly malignant cancers are diagnosed at an advanced stage where treatment options are limited and patient survival outcomes are poor. The biological and therapeutic challenges posed by hepatobililiary cancers such as hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) are daunting, emphasizing a critical need to review and assess current and evolving basic, translational, and clinical research focused on addressing the critical obstacles that continue to limit progress towards achieving significant improvements in HCC and CCA clinical management and patient survival outcomes. Towards this goal, this special edition of Advances in Cancer Research is focused on providing a comprehensive, timely and authoritative reviews covering such topics of significant scientific and clinical relevance, including hepatobiliary cancer risk mechanisms and risk-predictive molecular biomarkers; causes and functional intricacies of inter- and intratumor heterogeneity; novel insights into the role of tumor microenvironment and key signaling pathways in promoting hepatobiliary cancer progression, therapeutic resistance and immunosuppression; emerging biomarkers of HCC and CCA prognosis; advances in molecular genomics for personalizing tumor classification and targeted therapies; innovative preclinical cell culture modeling for hepatobiliary cancer drug discovery; and current and emerging trends in hepatobiliary cancer molecular therapeutic targeting and immunotherapies.

Baculovirus Expression Protocols, Second Edition, provides the detailed steps required to perform the techniques involved with the use of baculoviruses and insect cell culture and discusses problems that may be encountered. This newly-revised and updated edition provides a cutting edge step-by-step guide for biochemists, molecular biologists, biochemical engineers and others using the BEVS and/or insect cells for producing recombinant proteins. Furthermore, Baculovirus Expression Protocols, Second Edition, provides assistance to scientists and engineers interested in developing and producing baculovirus insecticides. Authors list all available insect cell lines and provide methods for isolating new cell lines. The procedures involved in producing products, both at laboratory scale and large scale, are discussed, as well as the production in insect larvae. It is hoped that this volume will not only aid the user in successfully completing the tasks described herein, but will also stimulate the development of improved techniques and new applications of baculoviruses and insect cell culture. Timely and thorough, this volume will become an essential reference for anyone using baculoviruses and insect cell culture.

Advances in Virus Research serial highlights new advances in the field with this new volume presenting interesting chapters. Each chapter is written by an international board of authors.

Viral Genomic RNA as a Single Translation Unit 100 Initiation Codon Choice and Translation in Plants 100 Conventional Scanning and Initiation 100 Non-AUG Initiation Codons in Plant Virus RNAs 101 Role of5'- and 3'- Noncoding Regions in Initiation of Translation 101 Access to Internal Genes 103 Divided versus Monopartite Genomes 104 Transcriptional Control: Subgenomic RNAs 104 Non-Orthodox Mechanisms of Initiation 107 Leaky Scanning 107 Internal Ribosome Entry Sites (IRES Elements) 107 Non-Orthodox Mechanisms of Elongation and Termination 108 Readthrough of Leaky Stop Codons 108 Ribosomal Frameshifiting 109 Proteolytic Processing 110 Chymotrypsin-like Serine or Cysteine Proteinases 112 Papain-like Cysteine Proteinases 112 Conclusions 113 References 114 5. Molecular Basis of Genetic Variability in RNA Viruses 121-141 Jozef J. Bujarski Introduction 121 Genetic Mechanisms of Variability 121 Mutation 121 Point Mutations 122 Insertions and Deletions 123 Frameshift Mutations 123 Mutant Stability 124 Effects of Mutations on Host-Virus Interactions 124 RNA Recombination 125 Natural Sequence Rearrangement 126 Recombination between Viral and Host RNAs 126 Role of RNA Structure 127 Role of Replicase Proteins 130 Pseudorecombination 131 Defective Interfering RNAs 132 Conclusions 134 Acknowledgements 136 References 136 viii 6. Genetic Variability and Evolution 143-159 F. Garcia-Arenal, A. Fraile, and J. M. Malpica Introduction 143 Variability under Experimental Conditions 143 Variability under Natural Conditions 145 Factors Determining Genetic Structure of Virus Populations 149 Founder Effects 149 Selection 150 Complementation 152 Conclusions 153 Acknowledgements 155 References 155 7. Molecular Basis of Virus Transport in Plants 161-182 Scott M.

Years ago when we were asked to write a book on the present-day knowledge of the molecular biology of poliovirus, we did not expect that such an apparently simple task could involve so much time and effort. Our writing was hampered by the fact that both of us are full time "workers," so that this monograph is mainly a spare time expedience. The main attention of this book focuses on a detailed review of the molecular biology of poliovirus and especially on the advances of the last decade; medical and environmental aspects are only briefly mentioned. Observations from older studies are considered in view of more recent information. Some of the older ob servations provided fundamental insights and paved the way for present day research; too often such data has been neglected or independently rediscovered. Today, poliovirus research has again attracted considerable interest. High points gained within the last few years were the elucidation of the complete nucleotide sequences of the RNAs of the three poliovinls serotypes and the corresponding vaccine strains, the demonstration of genome evolution during transmission of poliovirus in an epidemic, further characterization of the antigenic sites on the virus particle and of the antigenic drift, characterization of alternate conforma tional states of the virion capsid, the development of monoclonal antibodies against some of the virus proteins, observations on the role of the plasma membrane, cytoskeleton, and cytoplasmic membranes as mediators in the virus induced redirection of the synthetic machinery of the host cell, and characteriza"