Arboviruses: Molecular Biology, Evolution and Control
"a thorough and compelling review ... an outstanding book ... highly recommended" (Am. J. Trop. Med. Hyg.)
"high standard ... extremely timely ... a must-have book" (Vaccine)
"would suit any audience" (Micro. Today)
Caister Academic Press
Nikos Vasilakis and Duane J. Gubler
University of Texas Medical Branch, Galveston, USA and Emerging Infectious Diseases Program, Duke-NUS Graduate Medical School, Singapore; respectively
xii + 398
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Arthropod-borne viruses (arboviruses) are the causative agents of significant morbidity and mortality among humans and domestic animals globally. They are maintained in complex biological life cycles, involving a primary vertebrate host and a primary arthropod vector. While all known arboviruses are zoonotic pathogens, their emergence as human pathogens is associated with dramatic increases of human population growth leading to uncontrolled urbanization, changes in land and water use, changes in agricultural practices, new irrigation systems and deforestation.
This book brings together a panel of expert arbovirologists to produce a timely review of the rapidly expanding arbovirus research literature. In addition authors identify the most pressing questions that remain to be answered, thus providing a stimulus for future research. Topics include: taxonomy, genome organization, virus-host and virus-vector interactions, evolutionary history, role of vertical transmission in arbovirus maintenance and evolution, epidemiology, arbovirus replication, pathogenesis, arbovirus diagnostics and control, including vaccines, novel anti-viral drugs, RNA interference and genetically modified vectors. Essential reading for every arbovirologist and highly recommended for all virologists and public health officials.
"provides a thorough and compelling review on the current status of arbovirology ... Overall, Arboviruses: Molecular Biology, Evolution and Control is an outstanding book. An impressive team of contributors was involved in its conception, and each contributor provides an excellent review of their particular research niche. This is arguably the first comprehensive book devoted specifically to arboviruses to be published in the last few decades. The book is highly recommended for every arbovirologist whether it be a first-year graduate student or an established researcher." from Am. J. Trop. Med. Hyg.
"authored by prominent and well-known scientists in the arbovirus field. The author list is commendable and is a key selling point of this book ... The chapters are extremely detailed and well-written ... There is an effective use of figures and tables throughout each chapter, all of which are of a high standard ... extremely timely ... the way in which the book as a whole has been brought together is commendable, with a logical order of chapters, and a wide-range of subject matter ... the book should be considered a must-have book for both experienced researchers and students interested in studying arbovirology as well as scientists and policymakers wishing to increase their understanding and knowledge of emerging arboviruses." from Vaccine
"Leaders in the field, such as Marco Vignuzzi, Richard Kuhn and Goro Kuno, present chapters on basic and applied aspects of arbovirus biology on topics ranging from taxonomy, pathogenesis, vaccines and antivirals to the ability to generate genetically modified mosquitos ... this book would suit any audience." from Microbiology Today
Table of contents
1. The Arboviruses: Quo Vadis?
Duane J. Gubler and Nikos Vasilakis
Arthropod-borne viruses (arboviruses) are the causative agents of significant morbidity and mortality among humans and domestic animals globally. They are maintained in complex biological life cycles, involving a primary vertebrate host and a primary arthropod vector. These cycles exist in natural sylvatic or urban foci of transmission. Arboviruses may emerge from their ecologically distinct nidus when humans or domestic animals unknowingly encroach on their environment, leading to local, regional or in some instances global epidemics. The principal drivers of epidemic arboviral disease emergence are anthropogenic, fueled by uncontrolled human population growth, economic development and globalization, combined with societal and technological changes. Other factors contributing to arboviral disease emergence are environmental changes, including urbanization, changes in land and water use, agricultural and animal husbandry practices, new irrigation systems and deforestation. Unless these trends are controlled and eventually reversed, the future will likely see more widespread and larger epidemics of arboviral disease.
2. The Taxonomy of Arboviruses
Nicole C. Arrigo, Scott C. Weaver and Charles H. Calisher
The purpose of viral taxonomy, as with all taxonomy, is to categorize viruses in a way that reflects their evolutionary relatedness, and the taxonomy of arboviruses is based on the same principles as that of all other viruses. Arboviruses are considered together only because of their unique biological characteristics and complex natural cycles, and are not collectively a rational taxonomic grouping based on ancestry. Historically, the definition of an arbovirus is a virus transmitted between vertebrate hosts by hematophagous (blood-feeding) arthropods, such as mosquitoes, ticks, sandflies, and culicoids. However, recent findings brought about by remarkable advances and applications of molecular techniques and viral genetics have revealed the presence of "arthropod viruses" (sometimes called "insect-only viruses") within taxa traditionally including arboviruses, causing arbovirologists to reconsider the traditional definition of an arbovirus and to determine how best to organize them into a logical and useful taxonomic framework. Here we present a historical and contemporary perspective of arbovirus taxonomy, and provide a current listing of conventionally defined arboviruses, as well as those "arthropod viruses" currently challenging convention.
3. Genomic Organization of Arboviral Families
Nikos Vasilakis, Amy Lambert, N. James MacLachlan and Aaron C. Brault
Arboviruses (arthropod-borne viruses) are represented almost exclusively by viruses comprised of RNA genomes for which a number of genomic organization and replication strategies have been observed. Herein, we have reviewed five viral families that comprise the majority of arboviruses transmissible to humans and livestock including: alphaviruses (Togaviridae), flaviviruses (Flaviviridae), rhabdoviruses (Rhabdoviridae), bunyaviruses (Bunyaviridae) and reoviruses (Reoviridae). Descriptions of the overall genomic architecture, viral proteins and replicative strategies have been included and serve to compare and contrast the breadth of variation that can be observed among these diverse groups of viruses that are transmitted by arthropod vectors. This diversity indicates the likelihood of convergence of disparate viral groups for arthropod transmission yet such a comparison can serve to highlight conserved genetic strategies between dipartite viruses for elucidation of the evolutionary pressures imposed by the necessity for replication in both vertebrate and invertebrate hosts.
4. Host Metabolism and its Contribution in Flavivirus Biogenesis
Rushika Perera and Richard J. Kuhn
Intracellular communication is key to cellular homeostasis. During infection of their hosts, viruses require a subversion of normal cellular communication pathways such that attention is focused towards efficient viral replication and virion biogenesis. Thus, the cellular environment is converted to a viral replication factory. Many viruses achieve this by significantly rearranging the intracellular membrane environment to form 'viral cobwebs' that extend throughout the cytoplasm. These cobwebs increase membrane contact sites within the cell and enhance cellular communication through signaling and transport of raw materials required for viral replication. Any form of intracellular conversion is directly linked to the metabolic pathways that drive cellular homeostasis. This chapter will therefore focus on the specific cellular metabolic pathways that are hijacked by viruses to achieve the formation of these viral replication factories. Specifically, we discuss how flaviviruses achieve an optimal cellular environment for replication and how these mechanisms seem conserved across species barriers as they replicate in both the human host and mosquito vector.
5. Vector-borne Bunyavirus Pathogenesis and Innate Immune Evasion
Brian Friedrich, Birte Kalveram and Shannan L. Rossi
The family Bunyaviridae is comprised of viruses that include several human and veterinary pathogens of note with signs and symptoms ranging from hemorrhagic fever to severe encephalitis in humans and fetal malformations and abortion storms in livestock. These viruses are found on every continent except Antarctica and use a variety of methods for transmission ranging from direct spread between vertebrates, use of hemophilic insects, sexual transmission among insects and even thrips that infect plants. Two non-structural proteins, NSs and NSm, serve as major virulence factors which act to subvert the host anti-viral response by interrupting signaling cascades leading to interferon induction, suppressing transcription of interferon and other host-response genes, inhibiting interferon-stimulated genes, and modulating the regulation of cell death. This chapter will focus on virus-host interactions of the arthropod-borne genera orthobunyavirus, phlebovirus and nairovirus.
6. Vector-borne Rhabdoviruses
Ivan V. Kuzmin and Peter J. Walker
Rhabdoviruses constitute a large group of single-stranded negative-sense RNA viruses distinguished by their morphology and common phylogenetic origin. They infect a wide range of organisms including placental mammals, marsupials, birds, reptiles, fish, insects and plants. The majority of rhabdoviruses are arthropod-borne although some of them have adapted to circulation in vertebrate hosts without participation of arthropod vectors (such as lyssaviruses, novirhabdoviruses, spriviviruses and perhabdoviruses) or to circulation within insect populations (such as sigmaviruses). Rhabdoviruses have relatively simple genomes consisting of the five canonical genes (N, P, M, G and L) which may be overprinted, overlapped and interspersed with accessory genes. Despite the fact that the vesicular stomatitis virus has served as a model of negative-sense RNA viruses in various studies, many aspects of virus-host interactions, transmission and circulation patterns are still poorly understood. As appears from rhabdovirus pathobiology, even the canonical genes are multifunctional and serve for distinct functions in the diverse family representatives. Functions of the accessory genes are largely unknown. Rhabdoviruses pose global threat for public health, agri- and aquaculture, and to economy. Conversely, some of them have been successfully used for the development of novel recombinant biologics. The progress in molecular techniques facilitates virus characterization and discovery of novel pathogens but more studies in the laboratory and clinical setting are needed to understand pathobiology of rhabdoviruses and to design feasible mechanisms for prevention and control of rhabdoviral diseases.
7. Alphavirus - Host Interactions
Kate D. Ryman and William B. Klimstra
Members of the genus Alphavirus, family Togaviridae, are arthropod-borne viruses, mostly vectored in nature by specific mosquito species between various vertebrate reservoir hosts including birds, rodents, equids and non-human primates (NHPs) in classical arbovirus transmission cycles. The exceptions are the so-called salmonid alphaviruses, salmon pancreatic disease virus and its subtype, sleeping disease virus, which infect fish, causing mortality in farmed salmon and trout, and the southern elephant seal virus (SESV). The presence of SESV within lice suggests an arthropod-borne cycle, but the vector-host relationships have yet to be confirmed. The second genus in the family is Rubivirus, containing only the rubella virus, which shares genomic and structural features with the alphaviruses but is not an arbovirus and so not discussed further. Within the Alphavirus genus, viruses are grouped into four major subgroups by antibody cross-reactivity: the Semliki Forest (SF), Venezuelan equine encephalitis (VEE), eastern equine encephalitis (EEE) and western equine encephalitis (WEE) serocomplexes. Fascinatingly, recent phylogenetic evidence suggests that the salmonid alphaviruses may be the progenitors of the entire genus. As a consequence of their transmission cycle, the alphaviruses must be replication-competent in their mosquito vectors and reservoir hosts, which vary between viruses. It has become increasingly clear that these highly divergent hosts each exert strongly selective pressures on the viruses that constrain viral genetic variation but may also drive particular aspects of host interaction that result in disease. In this chapter, we will describe recent advances in our understanding of the characteristics of alphavirus interaction with vertebrate hosts, focusing upon the relationship of particular infection/replication characteristics to disease manifestations and immune responses.
8. Molecular Interactions Between Arboviruses and Insect Vectors: Insects' Immune Responses to Virus Infection
Natapong Jupatanakul and George Dimopoulos
Despite the efficient spread of arboviral diseases, the mosquito represents a bottleneck in the transmission of pathogenic viruses. Within the mosquito, arboviruses have to overcome several barriers, imposed by the mosquito innate immune system, microbiota and other factors, to reach the salivary glands from where they can be transmitted to a new host. Here we will address the molecular interactions between viruses and mosquito vectors with emphasis on the innate immune system and microbiota, and discuss their potential for the development of disease control strategies.
9. Genetic Diversity of Arboviruses
Kenneth A. Stapleford, Gonzalo Moratorio and Marco Vignuzzi
Arthropod-borne viruses (arboviruses) encompass a wide range of genetically distinct and diverse viral species, with many of these viral pathogens capable of causing severe disease in mammals and plants. Arboviruses are unique in that they must be able to infect and replicate in both invertebrate (mosquitoes, ticks, sand flies, midges, dipteran, and thrips) as well as vertebrate (humans, primates, birds, rodents) and plant hosts in order to maintain a successful viral lifecycle. To facilitate these processes, arboviruses have taken advantage of a wide range of genome compositions, structures, and organizations, as well as the ability to evolve and generate diverse populations within viral species. This unique genetic diversity, both at the genome structure level as well as the nucleotide level, plays essential roles in viral genome replication, transcription, translation, transmission, vector tropism, and pathogenesis. This chapter will introduce the role of genetic diversity in specific arboviruses and the implications of which the levels of diversity can play on the viral life cycle.
10. Ecological and Epidemiological Factors Influencing Arbovirus Diversity, Evolution and Spread
Roy A. Hall, Sonja Hall-Mendelin, Jody Hobson-Peters, Natalie A. Prow and John S. Mackenzie
The requirement for arboviruses to be transmitted between arthropod vectors and vertebrate hosts provides enormous complexity in their strategies to persist in populations and spread into new areas. In this chapter, we discuss ecological, environmental and anthropological factors that influence the spread, establishment and evolution of vector-borne viruses and the emergence of novel arboviral diseases. These topics include the introduction of viruses and vectors into new geographical regions, the adaption of viruses to new vectors and hosts and how these events influence the evolution of new viral strains, new vector-host relationships and the emergence of viral strains with enhanced virulence. The potential effects of climate change, deforestation, and the encroachment of human habitation and agriculture on the emergence and distribution of arboviral diseases are also discussed. In this context, we conclude that real-time arboviral surveillance will be crucial in the management and prevention of arboviral disease, and that enhanced viral detection strategies integrated into high-throughput, cost-effective surveillance systems are essential for monitoring the spread of arboviruses and identifying new and emerging vector-borne viruses in the future.
11. Role of Inter- and Intra-host Genetics in Arbovirus Evolution
Alexander T. Ciota and Gregory D. Ebel
The global expansion of arthropod-borne viruses (arboviruses) in recent decades has significantly increased the public health threat from these pathogens, but the inherently diverse nature of viral RNA genomes both within and between hosts and vectors makes accurately characterizing current and future threats from arboviral agents a challenge. Here, we review the contributions of studies of inter and intra-host arbovirus genetics to our understanding of the unique selective pressures shaping arbovirus evolution and the consequences of genetic change. In particular, we discuss how past studies have informed our knowledge of virus and host-specific differences in shaping arboviral swarms and how this equates to the potential for phenotypic and/or epidemiological shifts; and how current and future studies utilizing next generation technologies and methods are beginning to provide the tools to gain a deeper understanding of arbovirus evolution in relevant systems.
12. Arbovirus Genomics and Metagenomics
Adam Fitch, Matthew B. Rogers, Lijia Cui and Elodie Ghedin
The arboviruses are a diverse group of arthropod transmitted viruses belonging to several viral families, almost all containing RNA genomes. New methodologies in viral genomics have enabled the probing of the different genomic structures observed in this group, including segmented and non-segmented single and double stranded RNA. We review sequence-dependent targeted gene approaches and sequence-independent metagenomic methods for the characterization of arbovirus genomes. The rapid expansion in the number of arboviral sequencing projects, focused on both known viruses for molecular epidemiology studies and unknown viruses for novel strain discovery, has been enabled by the development of new high throughput sequencing technologies. Outbreaks of both known and novel arboviruses mean that full genome characterization will continue to be salient to both research and healthcare organizations, informing vaccine development while fostering viral pathogenicity studies.
13. Role of Vertical Transmission in Mosquito-borne Arbovirus Maintenance and Evolution
Robert B. Tesh, Bethany G. Bolling and Barry J. Beaty
Vertical transmission of arboviruses provides a unique mechanism for arbovirus maintenance during adverse environmental conditions and amplification in nature. The mechanisms by which most arboviruses are trans-seasonally maintained remain unclear. There is evidence for VT by either transovarial or transovum transmission of the virus from mother to progeny in each of the major arbovirus families. However, the VT rates observed in field and laboratory studies seem insufficient to maintain the viruses in nature. Stabilized infection may condition maintenance of arboviruses and insect specific viruses in the arbovirus families in nature. Stabilized infection of Drosophila melanogaster maintains Sigma virus (family Rhabdoviridae) in nature in the absence of horizontal amplification of the virus in a vertebrate host. LaCrosse virus may be maintained in Aedes triseriatus by stabilized infection. Stabilized infection could be a unifying mechanism for trans-seasonal maintenance of arboviruses and related viruses from different families. VT and long term persistent infections promote arbovirus evolution in vectors. Understanding the role of VT in maintenance, evolution, and emergence of arboviruses is critical to prevent and control these threats to public and animal health.
14. The Boundaries of Arboviruses: Complexities Revealed in Their Host Ranges, Virus-Host Interactions and Evolutionary Relationships
Reflecting the sharp increase in public health and veterinary problems caused by arboviruses in the past several decades, scientists worldwide have generated enormous amounts of data and publications about arboviruses and a variety of other related animal viruses currently not classified in this group of viruses on the basis of arbovirus definition. Upon a closer examination of the latter group of viruses, however, it has become clear that the definition of arbovirus, the tenets, and concepts on which arbovirology is established need to be re-evaluated for their ambiguity, absence of supporting evidence, inconsistency or difficulty of generalization, and an assortment of other problems in defining the boundaries between arboviruses and non-arboviruses. To understand the origins of those problematic issues, first, it is necessary to trace the early histories of virus-host interactions conducive to the evolution of biological transmission. Accordingly, viral associations with arthropods, vertebrates and even plants in both terrestrial and/or aquatic environments are examined. The emphases of the analysis are on the uniqueness of the biology of vectors, vertebrates, ecosystem, opportunity of virus-host contact, food chain, and the impacts of viral infection on hosts. The second foci of analysis concern the markers involved in the evolutionary process. Because virus-host interaction operating under particular ecological conditions is unique to each viral lineage, generalization of the markers among all arboviral lineages is difficult. Nevertheless, given rapidly accumulating useful information enriching the database, it is now possible to undertake such a study in at least a few arboviral lineages. In a study of flaviviruses, the history of host range shift, genome (or gene) length, and the motifs in the 3' UTR were found to be useful markers for elucidating the evolutionary history of the lineage. As byproducts of this review process, many problematic issues surfaced. They include definition and measurement of virulence, existence of vertebrate reservoir, non-viremic transmission, accuracy of molecular phylogeny without a support of empirical data, validity of in vitro experiments for the identification of genetic determinants of phenotypic shift, existence of the viruses which replicate in both arthropods and vertebrates (viruses with a biphylum host range) but without a need of biological transmission for survival, accuracy of host range of arboviruses and biological transmission in aquatic environments. Collectively, these issues and derived questions, coupled with the ambiguity of the boundaries of arboviruses, warrant an urgent re-assessment of the fundamentals of arbovirology.
15. Laboratory Diagnosis of Arboviruses
Amy J. Lambert and Robert S. Lanciotti
In recent years, there have been significant advances in the international capability for the diagnosis of arboviral infections. These advances have predominantly occurred in the field of nucleic acid-based diagnosis; driven by a growing diversity of highly transferable and relatively affordable molecular assays. These comparatively newly described molecular assays complement standard serological assays that continue to be applied preferentially in many laboratories for the detection of arboviral antibodies. In addition to nucleic acid-based and serological efforts, virus isolation remains the standard for arboviral diagnosis and is undertaken most often in cell culture. Here, we summarize a variety of classical and newly developed methods for arboviral diagnosis, including both serological and virus detection techniques. The utility of these approaches for application to human clinical and ecological samples in both diagnostic and research settings is discussed.
16. Conventional Vector Control: Evidence it Controls Arboviruses
Scott Ritchie and Gregor Devine
Arboviruses cause significant human morbidity and mortality. Most arboviral infections for which a vaccine is not registered are controlled by managing the mosquito vector. Unfortunately, 'evidence based' studies that provide proof that this impacts infection or disease are almost nonexistent. Many arboviral diseases, especially encephalitides such as St. Louis encephalitis and Murray Valley encephalitis, are so rare in time and space that sentinel animals and mosquito infection rates must be used as proxies for disease activity. Thus, the impact of vector control interventions on mosquito populations is often the only measure of success we have. That effect is assessed using a continuum of investigations that range from simple bioassays and small plot/semi-field trials (does the intervention kill the target vector?) to far larger and rarer field trials (does the intervention reduce populations of the target vector?). The logistics and cost of these larger trials restricts their uptake but they are a basic requirement for demonstrating operationally useful impacts. These evaluations (including those that measure impacts on the aquatic habitat) must demonstrate population level effects on adult vectors over significant scales. They must compare treated and untreated control areas under statistically robust designs. Of all the arboviral diseases, dengue is by far the most prevalent and widespread. Its transmission patterns are complex and driven by climate, herd immunity, a superbly adapted mosquito, and modern patterns of human movement. Despite its importance, just as for rarer arboviruses, myriad studies show the impact of dengue control strategies on mosquitoes but few demonstrate an effect on the transmission of the virus. This chapter highlights the difficulties of dengue management in modern urban environments and considers why it is so hard to emulate the modern day successes of many malaria control programs. It discusses whether an emphasis on managing the aquatic habitat is a historical hangover from the well-funded, vertically-managed eradication programs of the 1900s and notes the paucity of trials that support investment in any existing vector control tool. The limited control options and operational funds available suggest that the old paradigms of dengue prevention and eradication are no longer practicable and need to be augmented by more targeted but less ambitious outbreak responses that focus on the few tools that might justify the expense of deployment.
17. Biological Control of Arbovirus Vectors
Thomas Walker and Steven P. Sinkins
Biological control methods have been used against arbovirus vectors, in particular mosquitoes, to help prevent the transmission of diseases such as dengue and chikungunya. Biocontrol is can be an attractive alternative to more conventional vector control strategies that involve insecticides due to its potential to have minimal impact on the environment. Numerous methods have been employed against field mosquito populations including natural mosquito predators such as Toxorhynchites mosquitoes, copepods and fish. Pathogenic bacteria, viruses and fungi have been proposed or used as mechanisms to control vector mosquitoes by having species-specific lethal effects on target populations. Several extracellular mosquito symbionts: midgut Asaia bacteria, midgut bacteria and yeast also have the potential to be used to inhibit arboviral replication in mosquitoes. Significant advances have recently been made in using the endosymbiotic bacterium Wolbachia to reduce the vector competence of mosquitoes that transmit arboviruses. In this chapter, we outline the various biocontrol strategies that have been proposed for insect vectors and the current status of research examining their implementation.
18. RNA Interference: A Pathway to Arbovirus Control
Kathryn A. Hanley and Christy C. Andrade
Arboviruses are responsible for a high burden of established and emerging disease worldwide, but specific antiviral therapies are lacking for the vast majority of these pathogens. RNA interference (RNAi) plays a central role in controlling arbovirus infections in arthropod vectors, and although the role of RNAi in vertebrate immunity remains controversial, it is clear that exogenous small RNAs can be used to stimulate antiviral effectors in vertebrate hosts. Thus a robust effort has been made to design and test RNAi-based strategies for control of arbovirus infections and prevention of arbovirus transmission. This chapter reviews these efforts, which group into three general categories: (i) use of exogenous small RNAs to prevent or treat arbovirus infections in humans and domestic animals, (ii) generation of genetically-modified arthropod vectors that express antiviral small RNAs and thereby block transmission, and (iii) creation of recombinant arboviruses that possess target sites for host microRNAs (miRNAs) as live-attenuated vaccines. While these approaches all hold promise, there remain barriers to the safe and effective delivery of small RNAs and critical knowledge gaps regarding arbovirus-RNAi interactions that must be overcome before any of these approaches come to fruition.
19. Genetically Modified Vectors for Control of Arboviruses
Ken E. Olson and Alexander W.E. Franz
Arthropod-borne viruses (arboviruses) are maintained in nature by cycling between hematophagus arthropod vectors and vertebrate hosts. Medically important mosquito vectors (Aedes and Culex spp) and the arboviruses they transmit have increased their geographic range through human travel, trade and climate change. There are no vaccines or therapeutic drugs readily available to control most arboviruses leaving large segments of the world's human population at risk for disease. Arboviral disease prevention relies on vector control by eliminating breeding sites and using outdoor or indoor insecticides to reduce vector-human contact. These approaches are costly, they impact the environment and they are difficult to sustain. Despite vector control efforts, arboviral diseases continue to emerge in new geographic regions (eg. chikungunya in western hemisphere) or pose increasing threats to human health in urban areas (eg. dengue). New approaches are needed to impede arbovirus transmission and control the emergence, prevalence and spread of arboviruses. In this chapter, we will discuss genetically modified vectors (GMVs) as a potentially important advancement in vector control. This chapter will focus mainly on dengue viruses (DENVs) and the mosquito vector, Ae. aegypti, but will discuss other arboviruses of the families Flaviviridae and Togaviridae and their vectors where appropriate.
20. Arbovirus Vaccines
Scott B. Halstead
Arthropod-borne (Arbo) viruses are a broad group of human and veterinary pathogens that are transmitted by the bite of a member of the arthropod phylum, generally mosquitoes or ticks. This review provides basic information on the nature of diseases with a general description of ecology and global disease prevalence together with information on licensed vaccines or vaccines in development for 20 arboviral species belonging to four genera - Bunyaviridae, Flaviviridae, Reoviridae and Togaviridae.
21. Small Molecule Drug Development for Dengue Virus
Qing-Yin Wang and Pei-Yong Shi
Dengue virus imposes one of the largest social and economic burdens of any mosquito borne viral pathogen. Currently, there is no clinically approved vaccine or effective antiviral therapy available. Tremendous progresses have been made in the past decade towards development of antivirals for DENV. In this chapter, we summarize the current approaches in antivirals development and report the progress towards discovery of direct acting antivirals or host inhibitors against dengue virus infection. Concerted efforts have to be continuously undertaken and will eventually lead to an effective dengue therapy.
22. Arbovirology: Back to the Future
Robert B. Tesh and Charles H. Calisher
This chapter briefly reviews the origins and development of arbovirology as a discipline and the changes that have occurred in the focus, techniques and orientation of arbovirus research over time. Arbovirus research was initially patient- or disease-oriented and the focus was mainly on diagnosis, treatment and control. Currently, arbovirus research is primarily focused on the pathogenetic aspects of arboviral diseases and on the structural and genetic characteristics of their etiologic agents. The early emphasis on field work, virus isolation and shoe leather epidemiology has been largely replaced by laboratory-based molecular and genetic studies, non-cultural diagnostic techniques and computer modeling of arboviral cycles and outbreaks. Both types of research (field and laboratory-based) provide valuable insights into the emergence, prevention and control of arboviral diseases, but the older classical methods have recently fallen into disfavor. Some of the contributing factors leading to this situation are discussed and recommendations are provided on how to better balance the teaching, funding and practice of arbovirology.
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(EAN: 9781910190210 9781910190227 Subjects: [microbiology] [virology] [medical microbiology] )