Masayuki Machida and Katsuya Gomi
from National Institute of Advanced Industrial Science and Technology (AIST) and Tohoku University (respectively) present a new book
Aspergillus: Molecular Biology and Genomics.
The publishered announced today that this
book is available for immediate dispatch. Full details at
horizonpress.com/aspergillusFurther reading:
Aspergillus: Molecular Biology and GenomicsLabels: aspergillus, Aspergillus flavus, Aspergillus niger, Aspergillus oryzae
Kathryn A. Hanley and Scott C. Weaver
from New Mexico State University and University of Texas Medical Branch (respectively) present a new book
Frontiers in Dengue Virus Research.
The publishered announced today that this
book is available for immediate dispatch. Full details at
horizonpress.com/dengueFurther reading:
Frontiers in Dengue Virus ResearchLabels: dengue, Dengue research, Dengue virology
Applications of Metagenomics in Plant-microbe Interactions
The interactions between
microbes and plants make the major contribution to the biotic components of soils, the most diverse habitats on Earth. Plants play central roles in providing nutrient input into the soil, both through microbially-mediated decomposition of plant matter, and through the direct provision of photosynthate derived root exudates. These nutrients support large and diverse
microbial communities, many of which provide direct benefit to the plant. The interplay between plants and their microbial co-habitants is regulated by extensive chemical signalling. Most of what we know about these complex community interactions has been derived through study of organisms in pure culture, but it is well known that the vast majority of microbes have not been cultivated. We now have the opportunity to explore the interactions between plants and microbes through cultivation-independent study of the
microbial communities. While high-throughput DNA sequence analysis is an important tool for these studies, the immense richness and diversity of such communities present a strong mandate for the use of functional
metagenomics strategies that involve a broad variety of screening methodologies to discover and study the currently unknown key biological processes.
Further readingLabels: Biotic components of soils, metagenomics, microbial communities, plant-microbe interactions
Applications of Metagenomics to the Human Microbiome
Genomics came of age when we began to witness a greater level of
microbial diversity within species than previously anticipated. This laid the foundation for generating genomic sequence data from whole environments without first using a culturing step, a field of research now known as
metagenomics. Metagenomics can be defined as the genomic analysis of microorganisms by direct extraction and cloning of DNA from an assemblage of microorganisms. The availability of next generation sequencing technologies such as 454 pyrosequencing have made it such that a cloning step is no longer essential for metagenomic projects. The National Institutes of Health launched a Human Microbiome initiative with primary goals to determine if there is a core human microbiome, to understand the changes in the human microbiome that can be correlated with human health, and to develop new technological and bioinformatics tools to support these goals. Initial sequencing initiatives for this program are in place and include metagenomic sequencing to characterize the microbial communities from 15-18 body sites from at least 250 individuals. This effort has expanded to become a worldwide initiative.
Further readingLabels: 54 pyrosequencing, Human Microbiome, microbiome, Next generation sequencing technologies
Applications of Metagenomics to Industrial Bioproducts
Recent progress in mining the rich genetic resource of non-culturable microbes has led to the discovery of new genes, enzymes, and natural products. The impact of
metagenomics is witnessed in the development of commodity and fine chemicals, agrochemicals and pharmaceuticals where the benefit of enzyme-catalyzed chiral synthesis is increasingly recognized. Recovery of metabolic pathways and gene clusters involved in biosynthesis of antibiotics and bioactive molecules has increased the prospect of identifying useful natural and synthetic products for drug development. The discovery of biocatalysts operating optimally with high efficiency in conditions amenable to industrial processes requirements are key to successful development of food products, detergent additives, bioactive compounds, fuel alcohol and biodiesel, as well as optically active intermediates for chemical and drug synthesis.
Further readingLabels: Drug development, Industrial Bioproducts, Non-culturable microbes
Application of Metagenomics to Bioremediation
Metagenomics can improve strategies for monitoring the impact of pollutants on ecosystems and for cleaning up contaminated environments. Increased understanding of how microbial communities cope with pollutants will help assess the potential of contaminated sites to recover from pollution and increase the chances of bioaugmentation or biostimulation trials to succeed. Moreover, by providing direct access to the pool of environmental genomes without the bias of cultivation, metagenomics offers the possibility of exploring the vast diversity of degradation pathways of environmental microorganisms. This could lead to the design of more efficient customized strains/consortia for targeted use in bioremediation applications.
Further readingLabels: bioremediation
Metaproteomics
Microbial ecology is currently experiencing a renaissance spurred by the rapid development of molecular techniques and "omics" technologies in particular. As never before, these tools have allowed researchers in the field to produce a massive amount of information through in situ measurements and analysis of natural microbial communities, both vital approaches to the goal of unraveling the interactions of microbes with their environment and with one another. While genomics can provide information regarding the genetic potential of microbes, proteomics characterizes the primary end-stage product, proteins, thus conveying functional information concerning microbial activity. Advances in mass spectrometry instrumentation and methodologies, along with
bioinformatics approaches, have brought this analytic chemistry technique to relevance in the biological realm due to its powerful applications in proteomics. Mass spectrometry-enabled proteomics, including "bottom-up" and "top-down" approaches, is capable of supplying a wealth of biologically-relevant information, from simple protein cataloging of the proteome of a microbial community to identifying post-translational modifications of individual proteins.
Further readingLabels: Metaproteomics
Genomics and Metagenomics
The extensive suite of molecular-based approaches developed over the past decade has enabled the field of
metagenomics, the study of uncultured microorganisms. Paramont to metagenomic analysis is use of high-throughput DNA sequencing technologies, which with the advent of low cost next-generation methods is transforming metagenomics. The application of
metagenomics, to both global environments and microbes associated with a living host, has facilitated study of the functional ecology of
environmental microorganisms. Novel functional genes and environmental functional signatures can be retrieved using
metagenomics, and these can form the basis of hypothesis driven analyses of uncultured microorganisms. A with any technology, the daunting task is to understand and apply the growing number of
metagenomics sequences in the context of
microbial ecology and evolution.
Further reading
Metagenomics
The advent of
metagenomics has had a dramatic effect in the way we view and study the microbial world. By allowing the direct investigation of the vast majority of bacteria, as well as viruses and fungi, irrespective of their culturability and taxonomic identities,
metagenomics has not only changed microbiological theory and methods but also has challenged the classical concept of species. This newly evolved biological field has proven to be rich and comprehensive and is making important contributions to
microbial ecology, biodiversity,
bioremediation, bioprospection of natural products, medicine, and many other fields. The diversity of facets of
metagenomics as well as the multiplicity of its potential applications makes it difficult to find an ample but at the same time ordered account of this new discipline.
Further readingLabels: metagenomics
A new update on research in
Microbial Ecology Microbial Diversity and Phylogeny
Genomics and Metagenomics
Metaproteomics
Nucleic-Acid-based Characterization
Microarrays in Microbial Ecology
The Soil Environment
Plant Microbial Communities
Marine Microbial Environments
Ocean microbial communities
Human Microbial Environment
Wastewater Treatment
Bacterial Biofilms
Read more at:
Microbial EcologyLabels: Bacterial Biofilms, ecology, genomics, metagenomics, Metaproteomics, microarrays, microbial communities, Microbial Diversity, Microbial Environments, Phylogeny, Soil Environment, Wastewater
Introduction to Biofilms
Gonococcal Biofilms
Dental Plaque
Oral Microbial Communities
Gram-positive Biofilm Infections
Biofilms in Pasteurellaceae
Biofilm Formation by Vibrio cholerae
read more at: BiofilmsLabels: biofilms, Biofilms in Pasteurellaceae, Biofilms in Vibrio cholerae, Dental Plaque, Gonococcal Biofilms, Gram-positive Biofilm Infections, Introduction to Biofilms, Oral Microbial Communities
Microbial Diversity and Phylogeny
The small subunit ribosomal RNA gene (SSU rRNA) has been the cornerstone of
microbial ecology studies over the last 15 years, and has provided much of what we know about Bacterial and
Archaeal diversity and community structure, and has greatly aided microbial taxonomy.
Genomics is aiding our understanding of the relationships among closely related organisms, and ultimately of natural populations.
In a
recent study the available 16S rRNA genes from species type strains were examined. The most distant sequences in the median genus and family were about 4.4% and 14% different, respectively. The largest dissimilarity between a sequence and its closest relative in the same taxa (similar to single-linkage clustering distance) was 3.5% and 10% for the median genus and family. The ratio of the two values averaged less than 1.5 for all ranks, indicating that most taxa are not elongated, but are fairly spherical. When the near-full-length 16S rRNA gene sequences in the public databases were clustered into groups at proxy distances for species, genus, family and order, the number of clusters with time increased exponentially for all ranks documenting the enormous diversity of the microbial world.
from James R. Cole, Kostas Konstantinidis, Ryan J. Farris and James M. Tiedje
in Environmental Molecular MicrobiologyFurther reading:
Labels: Archaeal diversity, Microbial Diversity, Microbial taxonomy, Phylogeny
Metaproteomics
Microbial ecology is currently experiencing a renaissance spurred by the rapid development of molecular techniques and "omics" technologies in particular. As never before, these tools have allowed researchers in the field to produce a massive amount of information through in situ measurements and analysis of natural microbial communities, both vital approaches to the goal of unraveling the interactions of microbes with their environment and with one another. While
genomics can provide information regarding the genetic potential of microbes, proteomics characterizes the primary end-stage product, proteins, thus conveying functional information concerning microbial activity.
Advances in mass spectrometry instrumentation and methodologies, along with
bioinformatics approaches, have brought this analytic chemistry technique to relevance in the biological realm due to its powerful applications in proteomics. Mass spectrometry-enabled proteomics, including "bottom-up" and "top-down" approaches, is capable of supplying a wealth of biologically-relevant information, from simple protein cataloging of the proteome of a microbial community to identifying post-translational modifications of individual proteins.
from Brian D. Dill, Jacque C. Young, Patricia A. Carey and Nathan C. VerBerkmoes
in Environmental Molecular MicrobiologyFurther reading:
Labels: Bioinformatics, genomics, Mass spectrometry, Metaproteomics, microbial communities, Microbial community, microbial ecology, Omics technologies, Proteome, Proteomics
Soil Microbiology
Until fairly recently, the living soil has been considered as a functional black box that is intrinsically too difficult to be unravelled into its core components. However, this concept has changed with the advent of the modern methodologies. The intricacies of
microbial life in soil has been impacted by the advanced, mainly molecular-based, approaches that have been unleashed on the soil habitat in recent years. The application of molecular and other advanced methods (
cultivation-independent analyses) has provided exciting new insights into microbial life in soil.
Soil is an extremely diverse and complex habitat containing many microsites and gradients that form a range of different biogeochemical interfaces. Depending on the proportion of sand, silt and clay, the surface area in soil can vary from 11 cm
2 up to 8 million cm
2 per gram of soil
read more.... The aggregates formed by minerals, soil organic matter, fungal hyphae, roots and plant debris offer a range of potential niches for microorganisms with different lifestyles. The architecture of the soil pore network essentially defines the habitat colonized by the microorganisms and the pore space strongly influences the nature and extent of the interactions between the organisms inhabiting the soil. The heterogeneous physical structure of soil affects the spatial distribution of water, oxygen and nutrients, which in turn influences the composition and activity of the microbial communities themselves. As an example, the spatial distribution of bacteria in topsoil and subsoil was found to be different, but lateral variations in spatial distributions are also likely to occur.
In terms of their occurrence in microsites, bacteria can be found in soil as single cells but most often they occur as microcolonies, i.e. small agglomerates of cells that can be regarded as primative soil biofilms
read more.... Microorganisms are the major drivers of geochemical and biotransformation processes in soil. In concert with the soil's inorganic and organic constituents, microbes are influential in actively shaping the architecture of the soil matrix by the formation and restructuring of soil aggregates. In addition, the diversity of microbial communities is extremely high in most soils. There are only a few quantitative estimates of the numbers of microbial taxa that can co-exist in just a single gram of soil, but an advanced analysis of nucleic acid-based analyses, based on re-association kinetics, has suggested that prokaryotic diversity can reach 1 million species genomes per g, which by far exceeds the common estimates of bacterial richness in soil obtained from cultivation-based studies
read more....
A major driving force that spurs the microbial diversity of soil is the enormous heterogeneity of the soil habitat, allowing the formation of numerous niches. Different factors, such as the presence or absence of water, soil pH, temperature, redox potential and the soil organic matter content do not only influence the types of microbes colonizing the respective microniche but also their activity. All these factors can vary greatly between the different microhabitats and, thus, not only the composition but also the activity and interactions of the microbiota will largely vary due to the spatial and temporal heterogeneity between as well as within the microsites.
A key determinant of microbial fitness in soil is the ability of microbial cells to fine-tune their cellular metabolism to the abiotic and biotic conditions that prevail locally. In addition, the rate of adaptation of microorganisms to changing environmental conditions might be enhanced by horizontal gene transfer processes
read more.... Undoubtedly, the most important prerequisite for microbial life in soil is the availability of water. Next to being indispensable for microbial life, the water in soil carries dissolved gases, ions and nutrients to microorganisms, and, in cases of saturation, may quickly establish anaerobic conditions. For instance, an increase of the moisture content of soil can greatly influence the microbial communities that are locally present, in particular by connecting pore spaces in and among aggregates that were unconnected without water, thus increasing the aggregate connectivity. Predation by protozoa or
Bdellovibrio species will therefore be particularly enhanced in relatively wet soils.
from Kornelia Smalla and Jan Dirk van Elsas
in Environmental Molecular MicrobiologyFurther reading:
Labels: Cultivation-independent analysis, microbial communities, microbial ecology, soil microbiology
Genomics and Metagenomics
The early
genomics studies that began appearing in the 1980s progressed exponentially to the current state where the genome sequences of several hundred microbes, numerous eukaryotics, and thousands of viruses are available. Current estimates are that there are hundreds of partial genomes available and many other genome sequencing projects are also in progress. The real launch of the genomic era, however, began in the early 1990s with the availability of the complete genome sequence of
Haemophilus influenzae.
This study which was mind shattering at the time has now become routine protocol in many laboratories.
Genomics really came of age when we began to witness a greater level of microbial diversity within species than previously anticipated, lateral gene transfer, and the significance of phage and viral genomics. The field of genomics which gave us the first genome of a free living organism also laid the foundation for generating genomic sequence data from whole environments without first using a culturing step, a field of research now known as 'metagenomics'.
The term metagenomics was first used in the late 1990s, and was defined as the genomic analysis of microorganisms by direct extraction and cloning of DNA from an assemblage of microorganisms. The availability of 'next generation' sequencing technologies such as 454 pyrosequencing have made it such that a cloning step is no longer essential for metagenomic projects.
Further reading:
Labels: genomics, metagenomics
A new book on
Caliciviruses edited by Grant S. Hansman, Jason Jiang and Kim Y. Green has been announced today.
Caliciviruses are positive-sense, single stranded RNA viruses containing four recognized genera: Norovirus, Sapovirus, Lagovirus and Vesivirus. They are ubiquitous in the environment and are a major cause of disease in humans and many animals. Examples include Norwalk virus, a norovirus, thought to be responsible for roughly 90% of epidemic, non-bacterial outbreaks of gastroenteritis in humans around the world. Lack of a suitable cell culture system for human caliciviruses limited studies in previous decades, however the recent application of modern genomic technologies has revolutionized the field, leading to an explosion in calicivirus publications.
Caliciviruses: Molecular and Cellular VirologyEdited by: Grant S. Hansman, Jason Jiang and Kim Y. Green
Published: 2010
ISBN: 978-1-904455-63-9
Price: GB £159 or US $310
In this book, a panel of expert calicivirologists have selected the most important up-to-date research findings to produce timely and comprehensive reviews of the respective calicivirus field. Each chapter gives the reader a brief introduction to the topic followed by a descriptive discussion of the past and present research areas. Topics include: norovirus epidemiology; calicivirus contamination of the environment; genome organization and recombination, proteolytic cleavage and viral proteins; viral protein structures; virus-host interactions; calicivirus reverse genetics and replicon systems; feline calicivirus; swine calicivirus; murine norovirus pathogenesis and immunity; murine norovirus translation, replication and reverse genetics; and lagoviruses
read more ...Further reading:
CalicivirusesLabels: Caliciviruses, Lagovirus, Norovirus, Sapovirus, Vesivirus, virology, virology books
Antibiotic Resistance in Neisseria
Diseases caused by the pathogenic
Neisseria (
N. gonorrhoeae and
N.
meningitidis) have been successfully treated with antibiotics for the past 70 years. However, a disturbing trend worldwide is the increasing prevalence of strains with resistance to inexpensive and widely available antibiotics (e.g., penicillin, tetracycline and ciprofloxacin) and the emergence of strains exhibiting decreased susceptibility to effective antibiotics that are expensive and not always available (e.g. third-generation cephalosporins and the newer macrolides).
Given the global nature of
gonococcal and meningococcal diseases, the worldwide distribution of antibiotics, differing social practices in controlling and monitoring antibiotic availability, and geographical differences in treatment regimens, it is likely that the global problem of antibiotic resistance will continue (and worsen) in the foreseeable future. By understanding the mechanisms of antibiotic resistance in gonococci and meningococci, resistance to antibiotics currently in clinical practice can be anticipated and the design of novel antimicrobials to circumvent this problem can be undertaken more rationally.
A recent publication reviews the genetic and physiologic basis by which the
pathogenic Neisseria developed resistance to historically important antibiotics and how resistance to newer antibiotics is emerging
read more ...from William M. Shafer, Jason P. Folster and Robert A. Nicholas
in Neisseria: Molecular Mechanisms of PathogenesisLabels: antibiotic resistance, meningococcal
Neisseria and Apoptosis
A number of pathogens, including viruses, bacteria, and parasites, have evolved mechanisms to subvert apoptosis by either positively or negatively modulating host defenses. In particular, the inhibition of the apoptotic process by microbial pathogens has previously demonstrated importance in securing intracellular niches, which may be an important mechanism for microbial survival, replication or immune evasion.
Similarly, the induction of apoptosis may be beneficial to pathogens by promoting escape from host cells or diminishing their effector functions, again promoting immune evasion.
Conflicting studies have reported that infection with the facultative intracellular pathogens
Neisseria gonorrhoeae and Neisseria meningitidis can either inhibit or induce apoptosis. Reports on
Neisserial influence on the apoptotic response of host cells have been published consistently for almost ten years and will be the focus of this chapter.
Overall, it seems that
Neisseria species more often inhibit apoptosis, and this inhibition may allow time for adaptation to a new environment, intracellular replication, or immune evasion presumably leading to the spread of infection
read more ...from Sarah A. Follows and Paola Massari
in Neisseria: Molecular Mechanisms of PathogenesisLabels: Apoptosis, Neisseria, Neisseria gonorrhoeae, Neisseria meningitidis
Neisseria and Complement
Neisseria gonorrhoeae and
Neisseria meningitidis have evolved intricate mechanisms to evade killing by the complement system. Binding of complement inhibitors, LOS sialylation and expression of capsular polysaccharide in the case of
N. meningitidis all play key roles in enabling these bacteria to evade complement.
The multiplicity of complement evasion strategies reflects the importance of overcoming this immune barrier. Neisserial resistance to complement mediated killing appears to be restricted to humans and may provide an explanation for the host specificity of neisserial disease. Recent advances in our understanding of neisserial complement evasion strategies should aid in developing better animal models and vaccine design
read more ...from Lisa A. Lewis, E. Burrowes, Peter A Rice and Sanjay Ram
in Neisseria: Molecular Mechanisms of PathogenesisLabels: Complement, Neisseria, Neisseria gonorrhoeae, Neisseria meningitidis
Gonococcal Biofilms
Neisseria gonorrhoeae is an exclusive human pathogen. Recent studies have demonstrated that it utilizes two distinct mechanisms for entry into human urethral and cervical epithelial cells involving different bacterial surface ligands and host receptors. These studies have demonstrated that the gonococcus can form biofilms on glass surfaces and over human cells. There is evidence for the formation of gonococcal biofilms on human cervical epithelial cells during natural disease and further evidence that outer membrane blebbing by the gonococcus is crucial in biofilm formation over human cervical epithelial cells
read more ...from Michael Apicella, Megan L. Falsetta, Ryan Neil and Christopher Steichen
in Neisseria: Molecular Mechanisms of PathogenesisLabels: Gonococcal, Neisseria, Neisseria gonorrhoeae
Brief notes: Neisseria
The genus
Neisseria consists of commensal species that colonize the mucosal surfaces of many animals. Of the eleven species that colonize humans, only two are pathogens.
Neisseria meningitidis and
Neisseria gonorrhoeae often cause asymptomatic infections, a commensal-like behavior. Most gonoccocal infections are asymptomatic and self-resolving, and epidemic strains of the
meningococcus may be carried in more than 95% of a population where systemic disease occurs at less than 1% prevalence. Bacteria of the
Neisseria genus are Gram-negative and are included among the proteobacteria, a large group of Gram-negative organisms. The microorganisms exist as diplococci.
Neisseria gonorrhoeae and
Neisseria meningitidis are Gram-negative diplococci.
N. gonorrhoeae is the causative agent of gonorrhoea and is transmitted via sexual contact.
N. meningitidis is transmitted via respiratory droplets leading to colonization of the nasopharynx and can cause meningitis and septicemia.
- Neisseria: Molecular Mechanisms of Pathogenesis
- Microbiology books
Labels: brief notes, diplococci, gonococcus, gonorrhoea, gonorrhoeae, meningitidis, meningococcal, meningococcus, Neisseria, Neisseria gonorrhoeae
ABC Conference
February 27 - March 5, 2010 ATP-Binding Cassette (ABC) Proteins: From Multidrug Resistance to Genetic Diseases
Innsbruck, Austria
Further information 3rd FEBS Special Meeting on ABC Proteins - ABC2010
ABC2010 will cover all basic and applied aspects of ABC proteins, both in normal and cancer cells, as well as their important roles in genetic diseases as well as drug resistance phenomena in cancer or microbial systems. Leading scientists from all over the world and representatives of major pharmaceutical companies will present and discuss latest news on ABC proteins operating in bacteria, fungi, plants, parasites and humans. We were able to commit numerous leading experts to participate, with many new faces attending as plenary speakers.
Suggested reading: ABC Transporters in MicroorganismsLabels: ABC 2010, ATP Proteins, FEBS conference, multidrug resistance
Conference alert
September 12 - 16, 2010 8th INTERNATIONAL CONGRESS ON EXTREMOPHILES
Azores, Portugal
Further information EXTREMOPHILES 2010
An international forum to appreciate the current state of the art of Extremophiles and to discuss how science in this field can contribute to finding solutions to the challenges we face in the future.
Suggested reading: Archaea: New Models for Prokaryotic BiologyLabels: conferences, extremophile, extremophiles
Dengue is currently endemic in more than one hundred countries around the world. It causes approximately 50-100 million infections annually, including 250,000-500,000 cases of dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS). According to the World Health Organization (WHO), two fifths of the world population is at risk of dengue virus (DENV) infection.
It has been suggested that globalization and climate change have had a significant impact on the emergence of
DENV in new areas. No vaccine or therapy against DENV is currently approved for use in humans, and alternative strategies to control DENV infection are urgently needed, particularly because the design of such strategies may also inform efforts in vaccine design.
Current research focuses on the prophylaxis/therapeutic potential of monoclonal antibodies (MAbs) against DENV and the challenges to implementation of this strategy, including antibody-dependent enhancement (ADE), genetic variability of DENV strains, potential for selection of MAb escape variants, and financial cost. Also important are the recent immunologic and structural studies that have provided a new understanding of antibody-mediated neutralization mechanisms and protection against DENV and other flavivirus infections. These insights are having an important impact on the development of vaccines and antibody-based therapies.
from Ana P. Goncalvez, Robert H. Purcell, and Ching-Juh Lai
in Frontiers in Dengue Virus ResearchFurther reading:
Dengue VirusLabels: dengue, dengue fever, dengue virus
Dengue has emerged as the most common mosquito-borne viral disease of humans in the past three decades. There are no available vaccines or antivirals against
DENV. Currently, vector control is the only method for prevention of the disease. Development of a successful vaccine would require for it to be effective against all four DENV serotypes, economical, and provide long-term protection. Antivirals directed against one or more stages of the virus life cycle are likely to form an important part of dengue disease therapeutics. The strategies that have been used in the past towards development of an effective antiviral against dengue, as well as those being employed currently are discussed in light of information from structural biology, computational biology and molecular virology, highlighting the potential opportunities and obstacles to their use.
from Mayuri, Elisa La Bauve and Richard J. Kuhn
in Frontiers in Dengue Virus ResearchFurther reading:
Dengue VirusLabels: dengue, dengue fever, Dengue therapy, Dengue vaccine, dengue virus
A safe and effective vaccine for the control of
Dengue Virus disease is urgently needed and long overdue. Because each of the four dengue virus serotypes can cause the full spectrum of dengue disease, vaccination must protect against each serotype. An unprecedented number of vaccine candidates are in development and under clinical evaluation, with live attenuated vaccines being the most advanced. Considerable effort is also being made in the development of inactivated, subunit protein, virus vectored, and DNA vaccine candidates. The need to elicit protective immunity without predisposing for antibody-mediated enhanced disease, the need for rapid and tetravalent protection, and the need for an economical vaccine have presented challenges in the development pathway. Nevertheless, innovative research and development continues to provide solutions to these obstacles.
from Stephen S. Whitehead and Anna P. Durbin
in Frontiers in Dengue Virus ResearchFurther reading:
Dengue VirusLabels: dengue, dengue fever, dengue virus, Dengue Virus Vaccine
Dengue/dengue hemorrhagic fever is the most important vector-borne viral disease globally, with over half of the world's population living at risk of infection. While vaccines for other flaviviruses such as yellow fever, Japanese encephalitis and tick-borne encephalitis have been developed,
dengue vaccine development is complicated by the need to incorporate all four virus serotypes into a single formulation. The only way to prevent dengue transmission presently is to reduce the vector population. Research focuses on the latest information on mosquito-dengue virus interaction, with the overall goal of identifying areas of research where improved understanding would likely contribute to our ability to predict and prevent cyclical epidemics.
from Eng-Eong Ooi and Duane J. Gubler
in Frontiers in Dengue Virus ResearchFurther reading:
Dengue VirusLabels: dengue, dengue fever, dengue virus
Dengue Virus (DENV) produces a wide range of human illness, ranging from asymptomatic infections to hemorrhagic and potentially fatal disease. Severe disease is associated with high viremia, immune enhancement of sequential infections, and exacerbated inflammatory response.
DENV is sensed in mammalian cells by endosomal and cytoplasmic receptors and stimulates the type-1 interferon (IFNα/ β) response. Secreted IFNα/ β stimulates JAK/STAT signaling, which results in the activation of IFNα/ β- stimulated genes that lead the infected cells toward the establishment of an antiviral response. Genomic technology has enabled the identification of a remarkable list of genes induced in human host cells in response to DENV infection. The results define antiviral and pro-inflammatory responses mainly composed of IFNα/ β- induced genes, which likely participate in the regulation of the immune response and vascular leakage during acute illness. DENV counteracts the IFNα/ β response of the host.
The evidence indicates that non-structural proteins of DENV weaken IFNα/ β signaling, causing reduced activation of IFNα/ β-induced genes. The increased virus uptake, weakened host cell defense, and unrestrained inflammatory response likely predispose patients to develop severe illness. The unveiling of these virus-host interactions leads to a better understanding of dengue pathogenesis, and to innovative diagnostic and therapeutic approaches.
from Jorge L. Muñoz-Jordán and Irene Bosch
in Frontiers in Dengue Virus ResearchFurther reading:
Dengue VirusLabels: dengue, dengue fever, dengue virus
As for all plus-stranded RNA viruses, dengue virus (DENV) genomic RNA is infectious. Transfection of full length DENV RNA genome into a susceptible cell triggers a complete cycle of viral replication. Construction of cDNA clones together with reverse genetics has proven to be a valuable tool to uncover genetic determinants of viral replication and to understand the function of the viral untranslated regions (UTRs).
Translation initiation and initiation of RNA synthesis occur at the 5' and 3' terminal regions of the genome, respectively, and rely on complex RNA-RNA and RNA- protein interactions. The DENV 5'UTR contains two defined RNA structures, Stem-Loop A and Stem-Loop B, which have distinct functions during the process of viral RNA synthesis. The viral 3'UTR contains three domains with conserved sequences and structures. In these domains, there are RNA elements that are essential for the replication process and other elements that act as enhancers of the process.
The 5' and 3' terminal regions of the viral RNA also carry inverted complementary sequences that mediate long-range RNA-RNA interactions and genome cyclization. It has been demonstrated for dengue and other flaviviruses that the circular conformation of the genome is a crucial determinant for viral replication.
In the last few years, a great deal has been learned about the mechanisms by which the viral UTRs function during DENV replication.
from Andrea Gamarnik
in Frontiers in Dengue Virus ResearchFurther reading:
Dengue VirusLabels: dengue, dengue fever, dengue virus
Replication of all positive-stranded RNA viruses investigated so far occurs in close association with virus-induced intracellular membrane structures. Dengue virus (DENV), as a member of the family Flaviviridae, also induces such extensive rearrangements of intracellular membranes, called replication complex (RC). These RCs seem to contain viral proteins, viral RNA and host cell factors. However, the biogenesis of the RC and the three-dimensional organisation is to the most part unclear.
from Sven Miller, Ines Romero-Brey, and Ralf Bartenschlager
in Frontiers in Dengue Virus ResearchFurther reading:
Dengue VirusLabels: dengue, dengue fever, dengue virus, Flaviviridae
Positive strand RNA viruses, including flaviviruses, generally utilize the translational machinery of the host to synthesize viral proteins either in a cap-dependent or cap-independent manner to produce polyprotein precursors which are then processed into mature proteins. Polyprotein processing is accomplished by the concerted action of host and viral proteases. While some viruses, such as the hepatitis C virus code for more than one protease to perform distinct functions, flaviviruses code for a novel two-component serine protease which participates in early and late stages of the viral life cycle.
from R. Padmanabhan and Alex Y. Strongin
in Frontiers in Dengue Virus ResearchFurther reading:
Dengue VirusLabels: dengue, dengue fever, dengue virus, flavivirus, Flaviviruses