| autophagy modulation as a potential therapeutic target for diverse diseases. | autophagy is an essential, conserved lysosomal degradation pathway that controls the quality of the cytoplasm by eliminating protein aggregates and damaged organelles. it begins when double-membraned autophagosomes engulf portions of the cytoplasm, which is followed by fusion of these vesicles with lysosomes and degradation of the autophagic contents. in addition to its vital homeostatic role, this degradation pathway is involved in various human disorders, including metabolic conditions, neurod ... | 2012 | 22935804 |
| autophagy in the regulation of pathogen replication and adaptive immunity. | autophagy is an evolutionarily conserved homeostatic process by which cells deliver cytoplasmic material for degradation into lysosomes. autophagy may have evolved as a nutrient-providing homeostatic pathway induced upon starvation, but with the acquisition of cargo receptors, autophagy has become an important cellular defence mechanism as well as a generator of antigenic peptides for major histocompatibility complex (mhc) presentation. we propose that autophagy efficiently protects against micr ... | 2012 | 22796170 |
| comprehensive biothreat cluster identification by pcr/electrospray-ionization mass spectrometry. | technology for comprehensive identification of biothreats in environmental and clinical specimens is needed to protect citizens in the case of a biological attack. this is a challenge because there are dozens of bacterial and viral species that might be used in a biological attack and many have closely related near-neighbor organisms that are harmless. the biothreat agent, along with its near neighbors, can be thought of as a biothreat cluster or a biocluster for short. the ability to comprehens ... | 2012 | 22768032 |
| therapeutic targeting of autophagy in disease: biology and pharmacology. | autophagy, a process of self-digestion of the cytoplasm and organelles through which cellular components are recycled for reuse or energy production, is an evolutionarily conserved response to metabolic stress found in eukaryotes from yeast to mammals. it is noteworthy that autophagy is also associated with various pathophysiologic conditions in which this cellular process plays either a cytoprotective or cytopathic role in response to a variety of stresses such as metabolic, inflammatory, neuro ... | 2013 | 23943849 |
| alphavirus-based vaccines. | alphavirus vectors have demonstrated high levels of transient heterologous gene expression both in vitro and in vivo and, therefore, possess attractive features for vaccine development. the most commonly used delivery vectors are based on three single-stranded encapsulated alphaviruses, namely semliki forest virus, sindbis virus and venezuelan equine encephalitis virus. alphavirus vectors have been applied as replication-deficient recombinant viral particles and, more recently, as replication-pr ... | 2014 | 24937089 |
| replicon rna viral vectors as vaccines. | single-stranded rna viruses of both positive and negative polarity have been used as vectors for vaccine development. in this context, alphaviruses, flaviviruses, measles virus and rhabdoviruses have been engineered for expression of surface protein genes and antigens. administration of replicon rna vectors has resulted in strong immune responses and generation of neutralizing antibodies in various animal models. immunization of mice, chicken, pigs and primates with virus-like particles, naked r ... | 2016 | 27827980 |
| mayaro virus infection in traveler returning from amazon basin, northern peru. | | 2012 | 22469145 |
| autophagy as an antimicrobial strategy. | autophagy is a process of lysosomal degradation that was originally described as a cellular response to adapt to a lack of nutrients and to enable the elimination of damaged organelles. autophagy is increasingly recognized as a process that is also involved in innate and adaptive immune responses against pathogens. studies on the regulation of autophagy have uncovered components of the autophagic cascade that can be manipulated pharmacologically. approaches to modulate autophagy may result in no ... | 2009 | 19681702 |
| autophagy, immunity, and microbial adaptations. | autophagy adjusts cellular biomass and function in response to diverse stimuli, including infection. autophagy plays specific roles in shaping immune system development, fueling host innate and adaptive immune responses, and directly controlling intracellular microbes as a cell-autonomous innate defense. as an evolutionary counterpoint, intracellular pathogens have evolved to block autophagic microbicidal defense and subvert host autophagic responses for their survival or growth. the ability of ... | 2009 | 19527881 |
| nationwide inventory of mosquito biodiversity (diptera: culicidae) in belgium, europe. | to advance our restricted knowledge on mosquito biodiversity and distribution in belgium, a national inventory started in 2007 (modirisk) based on a random selection of 936 collection points in three main environmental types: urban, rural and natural areas. additionally, 64 sites were selected because of the risk of importing a vector or pathogen in these sites. each site was sampled once between may and october 2007 and once in 2008 using mosquito magnet liberty plus traps. diversity in pre-def ... | 2012 | 22971463 |
| the role of b cells and humoral immunity in mycobacterium tuberculosis infection. | tuberculosis (tb) remains a serious threat to public health, causing 2 million deaths annually world-wide. the control of tb has been hindered by the requirement of long duration of treatment involving multiple chemotherapeutic agents, the increased susceptibility to mycobacterium tuberculosis infection in the hiv-infected population, and the development of multi-drug resistant and extensively resistant strains of tubercle bacilli. an efficacious and cost-efficient way to control tb is the devel ... | 2013 | 23468112 |
| intracellular pathogen detection by rig-i-like receptors. | the rig-i-like receptors (rlrs) rig-i, mda5, and lgp2 trigger innate immune responses against viral infections that serve to limit virus replication and to stimulate adaptive immunity. rlrs are cytosolic sensors for virus-derived rna and thus responsible for intracellular immune surveillance against infection. rlr signaling requires the adapter protein mavs to induce type i interferon, interferon-stimulated genes, and proinflammatory cytokines. this review focuses on the molecular and cell biolo ... | 2013 | 23611287 |
| applications of in vivo imaging in the evaluation of the pathophysiology of viral and bacterial infections and in development of countermeasures to bsl3/4 pathogens. | while preclinical and clinical imaging have been applied to drug discovery/development and characterization of disease pathology, few examples exist where imaging has been used to evaluate infectious agents or countermeasures to biosafety level (bsl)3/4 threat agents. viruses engineered with reporter constructs, i.e., enzymes and receptors, which are amenable to detection by positron emission tomography (pet), single photon emission tomography (spect), or magnetic resonance imaging (mri) have be ... | 2014 | 25008802 |
| human pathogenic bacteria, fungi, and viruses in drosophila: disease modeling, lessons, and shortcomings. | drosophila has been the invertebrate model organism of choice for the study of innate immune responses during the past few decades. many drosophila-microbe interaction studies have helped to define innate immunity pathways, and significant effort has been made lately to decipher mechanisms of microbial pathogenesis. here we catalog 68 bacterial, fungal, and viral species studied in flies, 43 of which are relevant to human health. we discuss studies of human pathogens in flies revealing not only ... | 2014 | 24398387 |
| tick infestation in birds and prevalence of pathogens in ticks collected from different places in germany. | the importance of ticks and tick-borne pathogens for human and animal health has been increasing over the past decades. for their transportation and dissemination, birds may play a more important role than wingless hosts. in this study, tick infestation of birds in germany was examined. eight hundred ninety-two captured birds were infested with ticks and belonged to 48 different species, of which blackbirds (turdus merula) and song thrushes (turdus philomelos) were most strongly infested. ground ... | 2016 | 27048511 |
| vaccines timeline. interview by philip cohen. | | 1999 | 10559053 |
| ribosomal frameshifting and transcriptional slippage: from genetic steganography and cryptography to adventitious use. | genetic decoding is not 'frozen' as was earlier thought, but dynamic. one facet of this is frameshifting that often results in synthesis of a c-terminal region encoded by a new frame. ribosomal frameshifting is utilized for the synthesis of additional products, for regulatory purposes and for translational 'correction' of problem or 'savior' indels. utilization for synthesis of additional products occurs prominently in the decoding of mobile chromosomal element and viral genomes. one class of re ... | 2016 | 27436286 |
| eating the enemy within: autophagy in infectious diseases. | autophagy is emerging as a central component of antimicrobial host defense against diverse viral, bacterial, and parasitic infections. in addition to pathogen degradation, autophagy has other functions during infection such as innate and adaptive immune activation. as an important host defense pathway, microbes have also evolved mechanisms to evade, subvert, or exploit autophagy. additionally, some fungal pathogens harness autophagy within their own cells to promote pathogenesis. this review wil ... | 2008 | 18772897 |
| a putative rna-interference-based immune system in prokaryotes: computational analysis of the predicted enzymatic machinery, functional analogies with eukaryotic rnai, and hypothetical mechanisms of action. | all archaeal and many bacterial genomes contain clustered regularly interspaced short palindrome repeats (crispr) and variable arrays of the crispr-associated (cas) genes that have been previously implicated in a novel form of dna repair on the basis of comparative analysis of their protein product sequences. however, the proximity of crispr and cas genes strongly suggests that they have related functions which is hard to reconcile with the repair hypothesis. | 2006 | 16545108 |
| probing protein structure by amino acid-specific covalent labeling and mass spectrometry. | for many years, amino acid-specific covalent labeling has been a valuable tool to study protein structure and protein interactions, especially for systems that are difficult to study by other means. these covalent labeling methods typically map protein structure and interactions by measuring the differential reactivity of amino acid side chains. the reactivity of amino acids in proteins generally depends on the accessibility of the side chain to the reagent, the inherent reactivity of the label ... | 2009 | 19016300 |
| interferon-inducible effector mechanisms in cell-autonomous immunity. | interferons (ifns) induce the expression of hundreds of genes as part of an elaborate antimicrobial programme designed to combat infection in all nucleated cells - a process termed cell-autonomous immunity. as described in this review, recent genomic and subgenomic analyses have begun to assign functional properties to novel ifn-inducible effector proteins that restrict bacteria, protozoa and viruses in different subcellular compartments and at different stages of the pathogen life cycle. severa ... | 2012 | 22531325 |
| noninvasive biophotonic imaging for studies of infectious disease. | according to world health organization estimates, infectious organisms are responsible for approximately one in four deaths worldwide. animal models play an essential role in the development of vaccines and therapeutic agents but large numbers of animals are required to obtain quantitative microbiological data by tissue sampling. biophotonic imaging (bpi) is a highly sensitive, nontoxic technique based on the detection of visible light, produced by luciferase-catalysed reactions (bioluminescence ... | 2010 | 20955395 |
| gas chromatography-mass spectroscopy analysis of bioactive petalostigma extracts: toxicity, antibacterial and antiviral activities. | petalostigma pubescens and petalostigma triloculare were common components of pharmacopeia's of multiple australian aboriginal tribal groupings which traditionally inhabited the areas in which they grow. among these groups, they had a myriad of medicinal uses in treating a wide variety of bacterial, fungal and viral infections. this study was undertaken to test p. pubescens and p. triloculare leaf and fruit extracts for the ability to inhibit bacterial and viral growth and thus validate australi ... | 2014 | 24914307 |
| directed changes in the number of double-stranded rna genomic segments in bacteriophage phi6. | bacteriophage phi6 has a genome of three segments of double-stranded rna. the segments are designated s, m, and l. each segment has a unique packaging site, pac, near the 5' end of the plus strand. the plus strands of the segments are normally packaged in the order s, m, l. chimeras of segment m and s in which segment m is at the 5' end of the plus strand can be stably incorporated into the virion; however, an independent segment s must be included along with normal segment l, even if it contain ... | 1998 | 9520468 |
| adding the third dimension to virus life cycles: three-dimensional reconstruction of icosahedral viruses from cryo-electron micrographs. | viruses are cellular parasites. the linkage between viral and host functions makes the study of a viral life cycle an important key to cellular functions. a deeper understanding of many aspects of viral life cycles has emerged from coordinated molecular and structural studies carried out with a wide range of viral pathogens. structural studies of viruses by means of cryo-electron microscopy and three-dimensional image reconstruction methods have grown explosively in the last decade. here we revi ... | 1999 | 10585969 |
| ceramide-rich platforms in transmembrane signaling. | recent evidence suggests that ceramide regulates stress signaling via reorganization of the plasma membrane. the focus of this review will be to discuss the mechanism by which acid sphingomyelinase (asmase)-generated ceramide initiates transmembrane signaling in the plasma membrane exoplasmic leaflet. in particular, we review the unique biophysical properties of ceramide that render it proficient in formation of signaling domains termed ceramide-rich platforms (crps), and the role of crps in the ... | 2010 | 20178791 |
| carbocyclic 5'-nor "reverse" fleximers. design, synthesis, and preliminary biological activity. | a series of 5'-nor carbocyclic "reverse" flexible nucleosides or "fleximers" have been designed wherein the nucleobase scaffold resembles a "split" purine as well as a substituted pyrimidine. this modification was employed to explore recognition by both purine and pyrimidine metabolizing enzymes. the synthesis of the carbocyclic fleximers and the results of their preliminary biological screening are described herein. | 2011 | 24312722 |
| diagnosis of barmah forest virus infection by a nested real-time sybr green rt-pcr assay. | barmah forest virus (bfv) is a mosquito borne (+) ssrna alphavirus found only in australia. it causes rash, myalgia and arthralgia in humans and is usually diagnosed serologically. we developed a real-time pcr assay to detect bfv in an effort to improve diagnosis early in the course of infection. the limit of detection was 16 genome equivalents with a specificity of 100%. fifty five serum samples from bfv-infected patients were tested by the pcr. 52 of 53 antibody-positive samples were pcr negat ... | 2013 | 23935816 |
| dominance effects of deleterious and beneficial mutations in a single gene of the rna virus ϕ6. | most of our knowledge of dominance stems from studies of deleterious mutations. from these studies we know that most deleterious mutations are recessive, and that this recessivity arises from a hyperbolic relationship between protein function (i.e., protein concentration or activity) and fitness. here we investigate whether this knowledge can be used to make predictions about the dominance of beneficial and deleterious mutations in a single gene. we employed a model system--the bacteriophage φ6- ... | 2014 | 24945910 |
| tom1, an arabidopsis gene required for efficient multiplication of a tobamovirus, encodes a putative transmembrane protein. | host-encoded factors play an important role in virus multiplication, acting in concert with virus-encoded factors. however, information regarding the host factors involved in this process is limited. here we report the map-based cloning of an arabidopsis thaliana gene, tom1, which is necessary for the efficient multiplication of tobamoviruses, positive-strand rna viruses infecting a wide variety of plants. the tom1 mrna is suggested to encode a 291-aa polypeptide that is predicted to be a multip ... | 2000 | 10944200 |
| nontemplated terminal nucleotidyltransferase activity of double-stranded rna bacteriophage phi6 rna-dependent rna polymerase. | the replication and transcription of double-stranded rna (dsrna) viruses occur within a polymerase complex particle in which the viral genome is enclosed throughout the entire life cycle of the virus. a single protein subunit in the polymerase complex is responsible for the template-dependent rna polymerization activity. the isolated polymerase subunit of the dsrna bacteriophage phi6 was previously shown to replicate and transcribe given rna molecules. in this study, we show that this enzyme als ... | 2008 | 18614640 |
| antiviral immunity directed by small rnas. | plants and invertebrates can protect themselves from viral infection through rna silencing. this antiviral immunity involves production of virus-derived small interfering rnas (virnas) and results in specific silencing of viruses by virna-guided effector complexes. the proteins required for virna production as well as several key downstream components of the antiviral immunity pathway have been identified in plants, flies, and worms. meanwhile, viral mechanisms to suppress this small rna-directe ... | 2007 | 17693253 |
| modulation of nf-κb signalling by microbial pathogens. | the nuclear factor-κb (nf-κb) family of transcription factors plays a central part in the host response to infection by microbial pathogens, by orchestrating the innate and acquired host immune responses. the nf-κb proteins are activated by diverse signalling pathways that originate from many different cellular receptors and sensors. many successful pathogens have acquired sophisticated mechanisms to regulate the nf-κb signalling pathways by deploying subversive proteins or hijacking the host si ... | 2011 | 21383764 |
| anti-infective properties of epigallocatechin-3-gallate (egcg), a component of green tea. | the consumption of green tea (camellia sinensis) has been shown to have many physiological and pharmacological health benefits. in the past two decades several studies have reported that epigallocatechin-3-gallate (egcg), the main constituent of green tea, has anti-infective properties. antiviral activities of egcg with different modes of action have been demonstrated on diverse families of viruses, such as retroviridae, orthomyxoviridae and flaviviridae and include important human pathogens lik ... | 2013 | 23072320 |
| visualization of neutrophil extracellular traps and fibrin meshwork in human fibrinopurulent inflammatory lesions: iii. correlative light and electron microscopic study. | neutrophil extracellular traps (nets) released from dead neutrophils at the site of inflammation represent webs of neutrophilic dna stretches dotted with granule-derived antimicrobial proteins, including lactoferrin, and play important roles in innate immunity against microbial infection. we have shown the coexistence of nets and fibrin meshwork in varied fibrinopurulent inflammatory lesions at both light and electron microscopic levels. in the present study, correlative light and electron micro ... | 2016 | 27917008 |
| outrunning the red queen: bystander activation as a means of outpacing innate immune subversion by intracellular pathogens. | originally described by the late evolutionary biologist leigh van valen, the red queen hypothesis posits that the evolutionary arms race between hosts and their pathogens selects for discrete, genetically encoded events that lead to competitive advantages over the other species. examples of immune evasion strategies are seen throughout the co-evolution of the mammalian immune system and pathogens, such as the enzymatic inactivation of nuclear factor-κb signaling or host translation by pathogen-e ... | 2016 | 27545071 |
| viral evasion of autophagy. | autophagy is an evolutionarily ancient pathway for survival during different forms of cellular stress, including infection with viruses and other intracellular pathogens. autophagy may protect against viral infection through degradation of viral components (xenophagy), by promoting the survival or death of infected cells, through delivery of toll-like receptor (tlr) ligands to endosomes to activate innate immunity, or by feeding antigens to mhc class ii compartments to activate adaptive immunity ... | 2007 | 18059171 |
| deconstructing host-pathogen interactions in drosophila. | many of the cellular mechanisms underlying host responses to pathogens have been well conserved during evolution. as a result, drosophila can be used to deconstruct many of the key events in host-pathogen interactions by using a wealth of well-developed molecular and genetic tools. in this review, we aim to emphasize the great leverage provided by the suite of genomic and classical genetic approaches available in flies for decoding details of host-pathogen interactions; these findings can then b ... | 2011 | 21979942 |
| intracellular recognition of pathogens and autophagy as an innate immune host defence. | pathogen recognition is the first and crucial step in innate immunity. molecular families involved in the recognition of pathogens and activation of the innate immune responses in immunoreactive cells include the toll-like receptor family in mammals and the peptidoglycan recognition protein (pgrp) family in drosophila, which sense microorganisms in an extracellular or luminal compartment. other emerging families are the intracellular recognition molecules for bacteria, such as nucleotide binding ... | 2011 | 21729928 |
| targeting antigens to dendritic cell receptors for vaccine development. | dendritic cells (dcs) are highly specialized antigen presenting cells of the immune system which play a key role in regulating immune responses. depending on the method of antigen delivery, dcs stimulate immune responses or induce tolerance. as a consequence of the dual function of dcs, dcs are studied in the context of immunotherapy for both cancer and autoimmune diseases. in vaccine development, a major aim is to induce strong, specific t-cell responses. this is achieved by targeting antigen t ... | 2013 | 24228179 |
| inhibition of acid sphingomyelinase by tricyclic antidepressants and analogons. | amitriptyline, a tricyclic antidepressant, has been used in the clinic to treat a number of disorders, in particular major depression and neuropathic pain. in the 1970s the ability of tricyclic antidepressants to inhibit acid sphingomyelinase (asm) was discovered. the enzyme asm catalyzes the hydrolysis of sphingomyelin to ceramide. asm and ceramide were shown to play a crucial role in a wide range of diseases, including cancer, cystic fibrosis, diabetes, alzheimer's disease, and major depressio ... | 2014 | 25228885 |
| ebolavirus requires acid sphingomyelinase activity and plasma membrane sphingomyelin for infection. | acid sphingomyelinase (asmase) converts the lipid sphingomyelin (sm) to phosphocholine and ceramide and has optimum activity at acidic ph. normally, asmase is located in lysosomes and endosomes, but membrane damage or the interaction with some bacterial and viral pathogens can trigger its recruitment to the plasma membrane. rhinovirus and measles viruses each require asmase activity during early stages of infection. both sphingomyelin and ceramide are important components of lipid rafts and are ... | 2012 | 22573858 |
| targeted treatments for cervical cancer: a review. | cervical cancer is the second most common cause of cancer death in women worldwide and the development of new diagnosis, prognostic, and treatment strategies merits special attention. although surgery and chemoradiotherapy can cure 80%-95% of women with early stage cancer, the recurrent and metastatic disease remains a major cause of cancer death. many efforts have been made to design new drugs and develop gene therapies to treat cervical cancer. in recent decades, research on treatment strategi ... | 2012 | 23144564 |
| virus-induced cd8+ t cells accelerate the onset of experimental autoimmune encephalomyelitis: implications for how viral infections might trigger multiple sclerosis exacerbations. | viral infections can exacerbate multiple sclerosis (ms) through poorly defined mechanisms. we developed an experimental system whereby infection with an asymptomatic neurotropic alphavirus caused a transient acceleration of experimental autoimmune encephalomyelitis (eae) without altering the expansion or differentiation of autoreactive cd4+ t cells. instead, this effect on the clinical course of eae depended on cd8+ t cells that neither participate in viral clearance nor induce neuropathology in ... | 2013 | 23602715 |
| therapeutic vaccine strategies against human papillomavirus. | high-risk types of human papillomavirus (hpv) cause over 500,000 cervical, anogenital and oropharyngeal cancer cases per year. the transforming potential of hpvs is mediated by viral oncoproteins. these are essential for the induction and maintenance of the malignant phenotype. thus, hpv-mediated malignancies pose the unique opportunity in cancer vaccination to target immunologically foreign epitopes. therapeutic hpv vaccination is therefore an ideal scenario for proof-of-concept studies of canc ... | 2014 | 26344626 |
| immunologic treatments for precancerous lesions and uterine cervical cancer. | development of hpv-associated cancers not only depends on efficient negative regulation of cell cycle control that supports the accumulation of genetic damage, but also relies on immune evasion that enable the virus to go undetected for long periods of time. in this way, hpv-related tumors usually present mhc class i down-regulation, impaired antigen-processing ability, avoidance of t-cell mediated killing, increased immunosuppression due to treg infiltration and secrete immunosuppressive cytoki ... | 2014 | 24667138 |
| perspectives for therapeutic hpv vaccine development. | human papillomavirus (hpv) infections and associated diseases remain a serious burden worldwide. it is now clear that hpv serves as the etiological factor and biologic carcinogen for hpv-associated lesions and cancers. although preventative hpv vaccines are available, these vaccines do not induce strong therapeutic effects against established hpv infections and lesions. these concerns create a critical need for the development of therapeutic strategies, such as vaccines, to treat these existing ... | 2016 | 27809842 |
| pathogen-inspired drug delivery to the central nervous system. | for as long as the human blood-brain barrier (bbb) has been evolving to exclude bloodborne agents from the central nervous system (cns), pathogens have adopted a multitude of strategies to bypass it. some pathogens, notably viruses and certain bacteria, enter the cns in whole form, achieving direct physical passage through endothelial or neuronal cells to infect the brain. other pathogens, including bacteria and multicellular eukaryotic organisms, secrete toxins that preferentially interact with ... | 2014 | 25610755 |
| jatropha gossypiifolia l. (euphorbiaceae): a review of traditional uses, phytochemistry, pharmacology, and toxicology of this medicinal plant. | jatropha gossypiifolia l. (euphorbiaceae), widely known as "bellyache bush," is a medicinal plant largely used throughout africa and america. several human and veterinary uses in traditional medicine are described for different parts and preparations based on this plant. however, critical reviews discussing emphatically its medicinal value are missing. this review aims to provide an up-to-date overview of the traditional uses, as well as the phytochemistry, pharmacology, and toxicity data of j. ... | 2014 | 25002902 |
| genetic dissection of the host tropism of human-tropic pathogens. | infectious diseases are the second leading cause of death worldwide. although the host multitropism of some pathogens has rendered their manipulation possible in animal models, the human-restricted tropism of numerous viruses, bacteria, fungi, and parasites has seriously hampered our understanding of these pathogens. hence, uncovering the genetic basis underlying the narrow tropism of such pathogens is critical for understanding their mechanisms of infection and pathogenesis. moreover, such gene ... | 2015 | 26407032 |
| drosophila as a model for antiviral immunity. | the fruit fly drosophila melanogaster has been successfully used to study numerous biological processes including immune response. flies are naturally infected with more than twenty rna viruses making it a valid model organism to study host-pathogen interactions during viral infections. the drosophila antiviral immunity includes rna interference, activation of the jak/stat and other signaling cascades and other mechanisms such as autophagy and interactions with other microorganisms. here we revi ... | 2010 | 21541000 |
| the drosophila imd pathway in the activation of the humoral immune response. | the imd pathway signaling plays a pivotal role in the drosophila defense against bacteria. during the last two decades, significant progress has been made in identifying the components and deciphering the molecular mechanisms underlying this pathway, including the means of bacterial sensing and signal transduction. while these findings have contributed to the understanding of the immune signaling in insects, they have also provided new insights in studying the mammalian nf-κb signaling pathways. ... | 2013 | 23721820 |
| uvc irradiation for pathogen reduction of platelet concentrates and plasma. | besides the current efforts devoted to microbial risk reduction, pathogen inactivation technologies promise reduction of the residual risk of known and emerging infectious agents. a novel pathogen reduction process for platelets, the theraflex uv-platelets system, has been developed and is under clinical evaluation for its efficacy and safety. in addition, proof of principle has been shown for uvc treatment of plasma units. the pathogen reduction process is based on application of uvc light of a ... | 2011 | 21779205 |
| validation of aedes aegypti aag-2 cells as a model for insect immune studies. | the understanding of mosquito immune responses can provide valuable tools for development of novel mosquito control strategies. aiming the study at insect innate immunity, continuous insect cell lines have been established and used as research tools due to the fact that they constitute more homogeneous, sensitive, and reproducible systems than the insects from which they originated. more recently, aag-2, an aedes aegypti cell lineage, began to be frequently used as a model for studies of mosquit ... | 2012 | 22827926 |
| actin is an evolutionarily-conserved damage-associated molecular pattern that signals tissue injury in drosophila melanogaster. | damage-associated molecular patterns (damps) are molecules released by dead cells that trigger sterile inflammation and, in vertebrates, adaptive immunity. actin is a damp detected in mammals by the receptor, dngr-1, expressed by dendritic cells (dcs). dngr-1 is phosphorylated by src-family kinases and recruits the tyrosine kinase syk to promote dc cross-presentation of dead cell-associated antigens. here we report that actin is also a damp in invertebrates that lack dcs and adaptive immunity. a ... | 2016 | 27871362 |
| mosquito-transmitted viruses - the great brazilian challenge. | arboviruses pose a serious threat to public health worldwide, overloading the healthcare system and causing economic losses. these viruses form a very diverse group, and in brazil, arboviruses belonging to the families flaviviridae and togaviridae are predominant. unfortunately, the number of arboviruses increases in proportion with factors such as deforestation, poor sanitation, climate changes, and introduction of new viruses like chikungunya virus and zika virus. in brazil, dengue is endemic, ... | 2016 | 27818091 |
| molecular detection of flaviviruses and alphaviruses in mosquitoes (diptera: culicidae) from coastal ecosystems in the colombian caribbean. | arboviruses belonging to the genera flavivirus and alphavirus were detected in mosquitoes in a rural area of san bernardo del viento (córdoba, colombia). a total of 22,180 mosquitoes were collected, sorted into 2,102 pools, and tested by generic/nested reverse transcription-polymerase chain reaction. venezuelan equine encephalitis virus, dengue virus, west nile virus, st. louis encephalitis virus, yellow fever virus, and culex flavivirus were detected and identified by sequencing. the detection ... | 2016 | 27706377 |
| a field-deployable reverse transcription recombinase polymerase amplification assay for rapid detection of the chikungunya virus. | chikungunya virus (chikv) is a mosquito-borne virus currently transmitted in about 60 countries. chikv causes acute flu-like symptoms and in many cases prolonged musculoskeletal and joint pain. detection of the infection is mostly done using rt-rcr or elisa, which are not suitable for point-of-care diagnosis. | 2016 | 27685649 |
| the viral capping enzyme nsp1: a novel target for the inhibition of chikungunya virus infection. | the chikungunya virus (chikv) has become a substantial global health threat due to its massive re-emergence, the considerable disease burden and the lack of vaccines or therapeutics. we discovered a novel class of small molecules ([1,2,3]triazolo[4,5-d]pyrimidin-7(6h)-ones) with potent in vitro activity against chikv isolates from different geographical regions. drug-resistant variants were selected and these carried a p34s substitution in non-structural protein 1 (nsp1), the main enzyme involve ... | 2016 | 27545976 |
| alphavirus infection: host cell shut-off and inhibition of antiviral responses. | alphaviruses cause debilitating disease in humans and animals and are transmitted by blood-feeding arthropods, typically mosquitoes. with a traditional focus on two models, sindbis virus and semliki forest virus, alphavirus research has significantly intensified in the last decade partly due to the re-emergence and dramatic expansion of chikungunya virus in asia, europe, and the americas. as a consequence, alphavirus-host interactions are now understood in much more molecular detail, and importa ... | 2016 | 27294951 |
| effects of an in-frame deletion of the 6k gene locus from the genome of ross river virus. | the alphaviral6kgene region encodes the two structural proteins 6k protein and, due to a ribosomal frameshift event, the transframe protein (tf). here, we characterized the role of the6kproteins in the arthritogenic alphavirus ross river virus (rrv) in infected cells and in mice, using a novel6kin-frame deletion mutant. comprehensive microscopic analysis revealed that the6kproteins were predominantly localized at the endoplasmic reticulum of rrv-infected cells. rrv virions that lack the6kprotein ... | 2016 | 26865723 |
| surveillance for western equine encephalitis, st. louis encephalitis, and west nile viruses using reverse transcription loop-mediated isothermal amplification. | collection of mosquitoes and testing for vector-borne viruses is a key surveillance activity that directly influences the vector control efforts of public health agencies, including determining when and where to apply insecticides. vector control districts in california routinely monitor for three human pathogenic viruses including west nile virus (wnv), western equine encephalitis virus (weev), and st. louis encephalitis virus (slev). reverse transcription quantitative polymerase chain reaction ... | 2016 | 26807734 |
| global emergence of alphaviruses that cause arthritis in humans. | arthropod-borne viruses (arboviruses) may cause severe emerging and re-emerging infectious diseases, which pose a significant threat to human and animal health in the world today. these infectious diseases range from mild febrile illnesses, arthritis, and encephalitis to haemorrhagic fevers. it is postulated that certain environmental factors, vector competence, and host susceptibility have a major impact on the ecology of arboviral diseases. presently, there is a great interest in the emergence ... | 2015 | 26689654 |
| sindbis and middelburg old world alphaviruses associated with neurologic disease in horses, south africa. | old world alphaviruses were identified in 52 of 623 horses with febrile or neurologic disease in south africa. five of 8 sindbis virus infections were mild; 2 of 3 fatal cases involved co-infections. of 44 middelburg virus infections, 28 caused neurologic disease; 12 were fatal. middelburg virus likely has zoonotic potential. | 0 | 26583836 |
| syndromic approach to arboviral diagnostics for global travelers as a basis for infectious disease surveillance. | arboviruses have overlapping geographical distributions and can cause symptoms that coincide with more common infections. therefore, arbovirus infections are often neglected by travel diagnostics. here, we assessed the potential of syndrome-based approaches for diagnosis and surveillance of neglected arboviral diseases in returning travelers. | 2015 | 26372010 |
| evolutionary genetics and vector adaptation of recombinant viruses of the western equine encephalitis antigenic complex provides new insights into alphavirus diversity and host switching. | western equine encephalitis virus (weev), highlands j virus (hjv), and fort morgan virus (fmv) are the sole representatives of the wee antigenic complex of the genus alphavirus, family togaviridae, that are endemic to north america. all three viruses have their ancestry in a recombination event involving eastern equine encephalitis virus (eeev) and a sindbis (sin)-like virus that gave rise to a chimeric alphavirus that subsequently diversified into the present-day weev, hjv, and fmv. here, we pr ... | 2014 | 25463613 |
| in- silico exploration of thirty alphavirus genomes for analysis of the simple sequence repeats. | the compilation of simple sequence repeats (ssrs) in viruses and its analysis with reference to incidence, distribution and variation would be instrumental in understanding the functional and evolutionary aspects of repeat sequences. present study encompasses the analysis of ssrs across 30 species of alphaviruses. the full length genome sequences, assessed from ncbi were used for extraction and analysis of repeat sequences using imex software. the repeats of different motif sizes (mono- to penta ... | 2014 | 25606453 |
| chikungunya fever in canada: fever and polyarthritis in a returned traveller. | | 2014 | 24566646 |
| ccr2 deficiency promotes exacerbated chronic erosive neutrophil-dominated chikungunya virus arthritis. | chikungunya virus (chikv) is a member of a globally distributed group of arthritogenic alphaviruses that cause weeks to months of debilitating polyarthritis/arthralgia, which is often poorly managed with current treatments. arthritic disease is usually characterized by high levels of the chemokine ccl2 and a prodigious monocyte/macrophage infiltrate. several inhibitors of ccl2 and its receptor ccr2 are in development and may find application for treatment of certain inflammatory conditions, incl ... | 2014 | 24696480 |
| arthritogenic alphaviral infection perturbs osteoblast function and triggers pathologic bone loss. | arthritogenic alphaviruses including ross river virus (rrv), sindbis virus, and chikungunya virus cause worldwide outbreaks of musculoskeletal disease. the ability of alphaviruses to induce bone pathologies remains poorly defined. here we show that primary human osteoblasts (hobs) can be productively infected by rrv. rrv-infected hobs produced high levels of inflammatory cytokine including il-6. the rankl/opg ratio was disrupted in the synovial fluid of rrv patients, and this was accompanied by ... | 2014 | 24733914 |
| structural plasticity of the semliki forest virus glycome upon interspecies transmission. | cross-species viral transmission subjects parent and progeny alphaviruses to differential post-translational processing of viral envelope glycoproteins. alphavirus biogenesis has been extensively studied, and the semliki forest virus e1 and e2 glycoproteins have been shown to exhibit differing degrees of processing of n-linked glycans. however the composition of these glycans, including that arising from different host cells, has not been determined. here we determined the chemical composition o ... | 2014 | 24467287 |
| zoonotic encephalitides caused by arboviruses: transmission and epidemiology of alphaviruses and flaviviruses. | in this review, we mainly focus on zoonotic encephalitides caused by arthropod-borne viruses (arboviruses) of the families flaviviridae (genus flavivirus) and togaviridae (genus alphavirus) that are important in both humans and domestic animals. specifically, we will focus on alphaviruses (eastern equine encephalitis virus, western equine encephalitis virus, venezuelan equine encephalitis virus) and flaviviruses (japanese encephalitis virus and west nile virus). most of these viruses were origin ... | 2013 | 24427764 |
| surveillance for arboviral zoonoses in new zealand birds. | given the significant burden that emerging infectious diseases place on global economies and public health, the monitoring and mitigation of, and early response to, potential infectious diseases are of the highest priority. the objective of this study was to survey for known and other potential arboviral zoonoses in multiple bird species at four locations in new zealand. | 2013 | 24478919 |
| a genome-wide analysis of rna pseudoknots that stimulate efficient -1 ribosomal frameshifting or readthrough in animal viruses. | programmed -1 ribosomal frameshifting (prf) and stop codon readthrough are two translational recoding mechanisms utilized by some rna viruses to express their structural and enzymatic proteins at a defined ratio. efficient recoding usually requires an rna pseudoknot located several nucleotides downstream from the recoding site. to assess the strategic importance of the recoding pseudoknots, we have carried out a large scale genome-wide analysis in which we used an in-house developed program to d ... | 2013 | 24298557 |
| enhanced arbovirus surveillance with deep sequencing: identification of novel rhabdoviruses and bunyaviruses in australian mosquitoes. | viral metagenomics characterizes known and identifies unknown viruses based on sequence similarities to any previously sequenced viral genomes. a metagenomics approach was used to identify virus sequences in australian mosquitoes causing cytopathic effects in inoculated mammalian cell cultures. sequence comparisons revealed strains of liao ning virus (reovirus, seadornavirus), previously detected only in china, livestock-infecting stretch lagoon virus (reovirus, orbivirus), two novel dimarhabdov ... | 2013 | 24314645 |
| the role of e3 in ph protection during alphavirus assembly and exit. | alphaviruses are small enveloped viruses whose surface is covered by spikes composed of trimers of e2/e1 glycoprotein heterodimers. during virus entry, the e2/e1 dimer dissociates within the acidic endosomal environment, freeing the e1 protein to mediate fusion of the viral and endosome membranes. e2 is synthesized as a precursor, p62, which is cleaved by furin in the late secretory pathway to produce mature e2 and a small peripheral glycoprotein, e3. the immature p62/e1 dimer is acid resistant, ... | 2013 | 23864626 |
| molecular mechanisms involved in the pathogenesis of alphavirus-induced arthritis. | arthritogenic alphaviruses, including ross river virus (rrv), chikungunya virus (chikv), sindbis virus (sinv), mayaro virus (mayv), o'nyong-nyong virus (onnv), and barmah forest virus (bfv), cause incapacitating and long lasting articular disease/myalgia. outbreaks of viral arthritis and the global distribution of these diseases point to the emergence of arthritogenic alphaviruses as an important public health problem. this review discusses the molecular mechanisms involved in alphavirus-induced ... | 2013 | 24069610 |
| chikungunya virus capsid protein contains nuclear import and export signals. | chikungunya virus (chikv) is an alphavirus of the togaviridae family. after autoproteolytic cleavage, the chikv capsid protein (cp) is involved in rna binding and assembly of the viral particle. the monomeric cp is approximately 30 kda in size and is small enough for passive transport through nuclear pores. some alphaviruses are found to harbor nuclear localization signals (nls) and transport of these proteins between cellular compartments was shown to be energy dependent. the active nuclear imp ... | 2013 | 23984714 |
| dendritic cell immunoreceptor regulates chikungunya virus pathogenesis in mice. | chikungunya virus (chikv) is a mosquito-borne alphavirus responsible for recent epidemic outbreaks of debilitating disease in humans. alphaviruses are known to interact with members of the c-type lectin receptor family of pattern recognition proteins, and given that the dendritic cell immunoreceptor (dcir) is known to act as a negative regulator of the host inflammatory response and has previously been associated with rheumatoid arthritis, we evaluated dcir's role in response to chikv infection. ... | 2013 | 23487448 |
| a tyrosine-to-histidine switch at position 18 of the ross river virus e2 glycoprotein is a determinant of virus fitness in disparate hosts. | arthritogenic alphaviruses are human pathogens maintained in nature through alternating replication in vertebrates and mosquitoes. using chimeric viruses, we previously reported that replacement of the pe2 coding region of the t48 strain of ross river virus (rrv-t48) with that from the attenuated dc5692 strain, which differ by 7 amino acids, resulted in an attenuated disease phenotype in a mouse model of rrv-induced rheumatic disease. here, we demonstrate that introduction of one of these amino ... | 2013 | 23514884 |
| impact of wolbachia on infection with chikungunya and yellow fever viruses in the mosquito vector aedes aegypti. | incidence of disease due to dengue (denv), chikungunya (chikv) and yellow fever (yfv) viruses is increasing in many parts of the world. the viruses are primarily transmitted by aedes aegypti, a highly domesticated mosquito species that is notoriously difficult to control. when transinfected into ae. aegypti, the intracellular bacterium wolbachia has recently been shown to inhibit replication of denvs, chikv, malaria parasites and filarial nematodes, providing a potentially powerful biocontrol st ... | 2012 | 23133693 |
| adaptive changes in alphavirus mrna translation allowed colonization of vertebrate hosts. | members of the alphavirus genus are arboviruses that alternate replication in mosquitoes and vertebrate hosts. in vertebrate cells, the alphavirus resists the activation of antiviral rna-activated protein kinase (pkr) by the presence of a prominent rna structure (downstream loop [dlp]) located in viral 26s transcripts, which allows an eif2-independent translation initiation of these mrnas. this article shows that dlp structure is essential for replication of sindbis virus (sinv) in vertebrate ce ... | 2012 | 22761388 |
| cell-based analysis of chikungunya virus e1 protein in membrane fusion. | chikungunya fever is a pandemic disease caused by the mosquito-borne chikungunya virus (chikv). e1 glycoprotein mediation of viral membrane fusion during chikv infection is a crucial step in the release of viral genome into the host cytoplasm for replication. how the e1 structure determines membrane fusion and whether other chikv structural proteins participate in e1 fusion activity remain largely unexplored. | 2012 | 22520648 |
| reemergence of chikungunya virus in indian subcontinent. | chikungunya virus (chikv), a reemerging arboviral disease of public health concern is characterized by a triad of fever, rash and arthralgia. it was responsible for a number of epidemics in asia and africa. the severity of the current epidemic can be judged by the fact that an estimated 1.38 million people in india and one-third of the la reunion population (by april 2006) were affected by chikv. aedes aegypti and aedes albopictus are the major mosquitoes transmitting chikv in asia. various neur ... | 2010 | 23637474 |
| a quantitative real-time rt-pcr assay for the detection of venezuelan equine encephalitis virus utilizing a universal alphavirus control rna. | venezuelan equine encephalitis virus (veev) is an alphavirus from the family togaviridae that causes epizootic outbreaks in equids and humans in central and south america. so far, most studies use conventional reverse transcriptase pcr assays for the detection of the different veev subtypes. here we describe the development of a taqman quantitative real-time reverse transcriptase pcr assay for the specific detection and quantitation of all veev subtypes which uses in parallel a universal equine ... | 2016 | 28042576 |
| ancient recombination events and the origins of hepatitis e virus. | hepatitis e virus (hev) is an enteric, single-stranded, positive sense rna virus and a significant etiological agent of hepatitis, causing sporadic infections and outbreaks globally. tracing the evolutionary ancestry of hev has proved difficult since its identification in 1992, it has been reclassified several times, and confusion remains surrounding its origins and ancestry. | 2016 | 27733122 |
| gene expression studies in mosquitoes. | research on gene expression in mosquitoes is motivated by both basic and applied interests. studies of genes involved in hematophagy, reproduction, olfaction, and immune responses reveal an exquisite confluence of biological adaptations that result in these highly-successful life forms. the requirement of female mosquitoes for a bloodmeal for propagation has been exploited by a wide diversity of viral, protozoan and metazoan pathogens as part of their life cycles. identifying genes involved in h ... | 2008 | 19161831 |
| emerging role of lipid droplets in aedes aegypti immune response against bacteria and dengue virus. | in mammals, lipid droplets (lds) are ubiquitous organelles that modulate immune and inflammatory responses through the production of lipid mediators. in insects, it is unknown whether lds play any role during the development of immune responses. we show that aedes aegypti aag2 cells - an immune responsive cell lineage - accumulates lds when challenged with enterobacter cloacae, sindbis, and dengue viruses. microarray analysis of aag2 challenged with e.cloacae or infected with dengue virus reveal ... | 2016 | 26887863 |
| cytokine diedel and a viral homologue suppress the imd pathway in drosophila. | viruses are obligatory intracellular parasites that suffer strong evolutionary pressure from the host immune system. rapidly evolving viral genomes can adapt to this pressure by acquiring genes that counteract host defense mechanisms. for example, many vertebrate dna viruses have hijacked cellular genes encoding cytokines or cytokine receptors to disrupt host cell communication. insect viruses express suppressors of rna interference or apoptosis, highlighting the importance of these cell intrins ... | 2016 | 26739560 |
| serosurveillance of viral pathogens circulating in west africa. | sub-saharan africa is home to a variety of pathogens, but disease surveillance and the healthcare infrastructure necessary for proper management and control are severely limited. lassa virus, the cause of lassa fever, a severe hemorrhagic fever in humans is endemic in west africa. in sierra leone at the kenema government hospital lassa diagnostic laboratory, up to 70 % of acute patient samples suspected of lassa fever test negative for lassa virus infection. this large amount of acute undiagnose ... | 2016 | 27716429 |
| temporal variation in sindbis virus antibody prevalence in bird hosts in an endemic area in sweden. | sindbis virus (sinv) is a mosquito-borne bird virus that occasionally causes human disease in fennoscandia, suggested to have cyclic 7-year intervals between outbreaks. reliable data on human infections in sweden is however lacking. here we investigated the sinv antibody prevalence among birds in a swedish area endemic to sinv to scrutinize if a cyclic variation in antibody prevalence is present in the natural host of sinv. serum from birds were sampled in the summers of 2002-2004 and 2009 in th ... | 2016 | 27579607 |
| neurological sequelae resulting from encephalitic alphavirus infection. | the recent surge in viral clinical cases and associated neurological deficits have reminded us that viral infections can lead to detrimental, long-term effects, termed sequelae, in survivors. alphaviruses are enveloped, single-stranded positive-sense rna viruses in the togaviridae family. transmission of alphaviruses between and within species occurs mainly via the bite of an infected mosquito bite, giving alphaviruses a place among arboviruses, or arthropod-borne viruses. alphaviruses are found ... | 2016 | 27379085 |
| wolbachia biocontrol strategies for arboviral diseases and the potential influence of resident wolbachia strains in mosquitoes. | arboviruses transmitted by mosquitoes are a major cause of human disease worldwide. the absence of vaccines and effective vector control strategies has resulted in the need for novel mosquito control strategies. the endosymbiotic bacterium wolbachia has been proposed to form the basis for an effective mosquito biocontrol strategy. resident strains of wolbachia inhibit viral replication in drosophila fruit flies and induce a reproductive phenotype known as cytoplasmic incompatibility that allows ... | 2016 | 26925368 |
| loss of glycosaminoglycan receptor binding after mosquito cell passage reduces chikungunya virus infectivity. | chikungunya virus (chikv) is a mosquito-transmitted alphavirus that can cause fever and chronic arthritis in humans. chikv that is generated in mosquito or mammalian cells differs in glycosylation patterns of viral proteins, which may affect its replication and virulence. herein, we compare replication, pathogenicity, and receptor binding of chikv generated in vero cells (mammal) or c6/36 cells (mosquito) through a single passage. we demonstrate that mosquito cell-derived chikv (chikv mos) has s ... | 2015 | 26484530 |
| eastern equine encephalitis virus in mice ii: pathogenesis is dependent on route of exposure. | eastern equine encephalitis virus (eeev) is an alphavirus with a case fatality rate estimated to be as high as 75 % in humans and 90 % in horses. surviving patients often have long-lasting and severe neurological sequelae. at present, there is no licensed vaccine or therapeutic for eeev infection. this study completes the clinical and pathological analysis of mice infected with a north american strain of eeev by three different routes: aerosol, intranasal, and subcutaneous. such an understanding ... | 2015 | 26423229 |
| the virus-host interplay: biogenesis of +rna replication complexes. | positive-strand rna (+rna) viruses are an important group of human and animal pathogens that have significant global health and economic impacts. notable members include west nile virus, dengue virus, chikungunya, severe acute respiratory syndrome (sars) coronavirus and enteroviruses of the picornaviridae family.unfortunately, prophylactic and therapeutic treatments against these pathogens are limited. +rna viruses have limited coding capacity and thus rely extensively on host factors for succes ... | 2015 | 26287230 |
| production of a sindbis/eastern equine encephalitis chimeric virus inactivated cell culture antigen. | eastern equine encephalitis virus (eeev) is a medically important pathogen that can cause severe encephalitis in humans, with mortality rates ranging from 30 to 80%. unfortunately there are no antivirals or licensed vaccines available for human use, and laboratory diagnosis is essential to differentiate eeev infection from other pathogens with similar clinical manifestations. the arboviral diseases branch (adb) reference laboratory at the cdc division of vector-borne diseases (dvbd) produces ref ... | 2015 | 26205552 |
| tissue barriers to arbovirus infection in mosquitoes. | arthropod-borne viruses (arboviruses) circulate in nature between arthropod vectors and vertebrate hosts. arboviruses often cause devastating diseases in vertebrate hosts, but they typically do not cause significant pathology in their arthropod vectors. following oral acquisition of a viremic bloodmeal from a vertebrate host, the arbovirus disease cycle requires replication in the cellular environment of the arthropod vector. once the vector has become systemically and persistently infected, the ... | 2015 | 26184281 |
| an alphavirus temperature-sensitive capsid mutant reveals stages of nucleocapsid assembly. | alphaviruses have a nucleocapsid core composed of the rna genome surrounded by an icosahedral lattice of capsid protein. an insertion after position 186 in the capsid protein produced a strongly temperature-sensitive growth phenotype. even when the structural proteins were synthesized at the permissive temperature (28°c), subsequent incubation of the cells at the non-permissive temperature (37°c) dramatically decreased mutant capsid protein stability and particle assembly. electron microscopy co ... | 2015 | 26051211 |
| do we need a vaccine against chikungunya? | during the last decade, the chikungunya (chikv) virus has expanded its range of activity, conquering new territories and becoming an important global health threat. in particular, the challenge represented by the recent emergence of chikv in the americas has strengthened the need of a safe and effective vaccine. although research on vaccines against chikv has been slow, a few vaccine candidates have been tested over the years. inactivated and attenuated vaccine candidates have shown promising re ... | 2015 | 25971340 |