| dicer-2- and piwi-mediated rna interference in rift valley fever virus-infected mosquito cells. | rift valley fever virus (rvfv) is a phlebovirus (bunyaviridae family) transmitted by mosquitoes. it infects humans and ruminants, causing dramatic epidemics and epizootics in africa, yemen, and saudi arabia. while recent studies demonstrated the importance of the nonstructural protein nss as a major component of virulence in vertebrates, little is known about infection of mosquito vectors. here we studied rvfv infection in three different mosquito cell lines, aag2 cells from aedes aegypti and u4 ... | 2012 | 23175368 |
| the gef1 proton-chloride exchanger affects tombusvirus replication via regulation of copper metabolism in yeast. | replication of plus-strand rna viruses [(+)rna viruses] is performed by viral replicases, whose function is affected by many cellular factors in infected cells. in this paper, we demonstrate a surprising role for gef1p proton-chloride exchanger in replication of tomato bushy stunt virus (tbsv) model (+)rna virus. a genetic approach revealed that gef1p, which is the only proton-chloride exchanger in saccharomyces cerevisiae, is required for tbsv replication in the yeast model host. we also show t ... | 2012 | 23192874 |
| multiple functions of bcl-2 family proteins. | bcl-2 family proteins are the regulators of apoptosis, but also have other functions. this family of interacting partners includes inhibitors and inducers of cell death. together they regulate and mediate the process by which mitochondria contribute to cell death known as the intrinsic apoptosis pathway. this pathway is required for normal embryonic development and for preventing cancer. however, before apoptosis is induced, bcl-2 proteins have critical roles in normal cell physiology related to ... | 2013 | 23378584 |
| hyperresponsiveness of mice deficient in plasma-secreted sphingomyelinase reveals its pivotal role in early phase of host response. | plasma secretion of acid sphingomyelinase is a hallmark of cellular stress response resulting in the formation of membrane embedded ceramide-enriched lipid rafts and the reorganization of receptor complexes. consistently, decompartmentalization of ceramide formation from inert sphingomyelin has been associated with signaling events and regulation of the cellular phenotype. herein, we addressed the question of whether the secretion of acid sphingomyelinase is involved in host response during seps ... | 2012 | 23230083 |
| autophagy and viruses: adversaries or allies? | the autophagy pathway is an essential component of host defense against viral infection, orchestrating pathogen degradation (xenophagy), innate immune signaling, and certain aspects of adaptive immunity. single autophagy proteins or cassettes of the core autophagy machinery can also function as antiviral factors independently of the canonical autophagy pathway. moreover, to survive and propagate within the host, viruses have evolved a variety of strategies to evade autophagic attack and manipula ... | 2013 | 23391695 |
| chloroquine inhibits dengue virus type 2 replication in vero cells but not in c6/36 cells. | dengue viruses are the most important arthropod-borne viruses in terms of morbidity and mortality in the world. since there is no dengue vaccine available for human use, we have set out to investigate the use of chloroquine as an antiviral drug against dengue. chloroquine, an amine acidotropic drug known to affect intracellular exocytic pathways by increasing endosomal ph, was used in the in vitro treatment of vero and c6/36 cells infected with dengue virus type 2 (denv-2). real-time rt-pcr and ... | 2013 | 23431254 |
| identification of a candidate therapeutic autophagy-inducing peptide. | the lysosomal degradation pathway of autophagy has a crucial role in defence against infection, neurodegenerative disorders, cancer and ageing. accordingly, agents that induce autophagy may have broad therapeutic applications. one approach to developing such agents is to exploit autophagy manipulation strategies used by microbial virulence factors. here we show that a peptide, tat-beclin 1-derived from a region of the autophagy protein, beclin 1, which binds human immunodeficiency virus (hiv)-1 ... | 2013 | 23364696 |
| differential unfolded protein response during chikungunya and sindbis virus infection: chikv nsp4 suppresses eif2α phosphorylation. | chikungunya (chikv) and sindbis (sinv) are arboviruses belonging to the alphavirus genus within the togaviridae family. they cause frequent epidemics of febrile illness and long-term arthralgic sequelae that affect millions of people each year. both viruses replicate prodigiously in infected patients and in vitro in mammalian cells, suggesting some level of control over the host cellular translational machinery that senses and appropriately directs the cell's fate through the unfolded protein re ... | 2013 | 23356742 |
| divergent roles of autophagy in virus infection. | viruses have played an important role in human evolution and have evolved diverse strategies to co-exist with their hosts. as obligate intracellular pathogens, viruses exploit and manipulate different host cell processes, including cellular trafficking, metabolism and immunity-related functions, for their own survival. in this article, we review evidence for how autophagy, a highly conserved cellular degradative pathway, serves either as an antiviral defense mechanism or, alternatively, as a pro ... | 2013 | 24709646 |
| ires-based venezuelan equine encephalitis vaccine candidate elicits protective immunity in mice. | venezuelan equine encephalitis virus (veev) is an arbovirus that causes periodic outbreaks that impact equine and human populations in the americas. one of the veev subtypes located in mexico and central america (ie) has recently been recognized as an important cause of equine disease and death, and human exposure also appears to be widespread. here, we describe the use of an internal ribosome entry site (ires) from encephalomyocarditis virus to stably attenuate veev, creating a vaccine candidat ... | 2013 | 23351391 |
| specificity of resistance to dengue virus isolates is associated with genotypes of the mosquito antiviral gene dicer-2. | in contrast to the prevailing view that invertebrate immunity relies on broad-spectrum recognition and effector mechanisms, intrinsic genetic compatibility between invertebrate hosts and their pathogens is often highly specific in nature. solving this puzzle requires a better understanding of the molecular basis underlying observed patterns of invertebrate host-pathogen genetic specificity, broadly referred to as genotype-by-genotype interactions. here, we identify an invertebrate immune gene in ... | 0 | 23193131 |
| retargeting vesicular stomatitis virus glycoprotein pseudotyped lentiviral vectors with enhanced stability by in situ synthesized polymer shell. | the ability to introduce transgenes with precise specificity to the desired target cells or tissues is key to a more facile application of genetic therapy. here, we describe a novel method using nanotechnology to generate lentiviral vectors with altered recognition of host cell receptor specificity. briefly, the infectivity of the vesicular stomatitis virus glycoprotein (vsv-g) pseudotyped lentiviral vectors was shielded by a thin polymer shell synthesized in situ onto the viral envelope, and ne ... | 0 | 23327104 |
| visualizing the autophagy pathway in avian cells and its application to studying infectious bronchitis virus. | autophagy is a highly conserved cellular response to starvation that leads to the degradation of organelles and long-lived proteins in lysosomes and is important for cellular homeostasis, tissue development and as a defense against aggregated proteins, damaged organelles and infectious agents. although autophagy has been studied in many animal species, reagents to study autophagy in avian systems are lacking. microtubule-associated protein 1 light chain 3 (map1lc3/lc3) is an important marker for ... | 2013 | 23328491 |
| polio, still lurking in the shadows. | | 0 | 23325224 |
| crystal structure of glycoprotein c from rift valley fever virus. | rift valley fever virus (rvfv), like many other bunyaviridae family members, is an emerging human and animal pathogen. bunyaviruses have an outer lipid envelope bearing two glycoproteins, g(n) and g(c), required for cell entry. bunyaviruses deliver their genome into the host-cell cytoplasm by fusing their envelope with an endosomal membrane. the molecular mechanism of this key entry step is unknown. the crystal structure of rvfv g(c) reveals a class ii fusion protein architecture found previousl ... | 2013 | 23319635 |
| ifn production ability and healthy ageing: mixed model analysis of a 24 year longitudinal study in japan. | to track changes in interferon (ifn) production in healthy individuals to shed light on the effect these changes have on the course of healthy ageing. | 2013 | 23315513 |
| sumoylation is required for glycine-induced increases in ampa receptor surface expression (chemltp) in hippocampal neurons. | multiple pathways participate in the ampa receptor trafficking that underlies long-term potentiation (ltp) of synaptic transmission. here we demonstrate that protein sumoylation is required for insertion of the glua1 ampar subunit following transient glycine-evoked increase in ampa receptor surface expression (chemltp) in dispersed neuronal cultures. chemltp increases co-localisation of sumo-1 and the sumo conjugating enzyme ubc9 and with psd95 consistent with the recruitment of sumoylated prote ... | 2013 | 23326329 |
| mossy fiber-ca3 synapses mediate homeostatic plasticity in mature hippocampal neurons. | network activity homeostatically alters synaptic efficacy to constrain neuronal output. however, it is unclear how such compensatory adaptations coexist with synaptic information storage, especially in established networks. here, we report that in mature hippocampal neurons in vitro, network activity preferentially regulated excitatory synapses within the proximal dendrites of ca3 neurons. these homeostatic synapses exhibited morphological, functional, and molecular signatures of the specialized ... | 0 | 23312519 |
| human papillomavirus infection is inhibited by host autophagy in primary human keratinocytes. | human papillomavirus (hpv) infection is severely limited in its natural host, primary human keratinocytes. our data show hpv infectivity in primary keratinocytes is over 100- and 1,000-fold lower than in established keratinocyte cell lines niks and hacat, respectively. here, we show that the basal level of autophagy in primary human foreskin keratinocytes (hfks) is higher than in immortalized keratinocytes, and that hpv16 virions significantly induce autophagy in hfks. interestingly, hpv16 infec ... | 2013 | 23290079 |
| bioluminescent imaging and histopathologic characterization of weev neuroinvasion in outbred cd-1 mice. | western equine encephalitis virus (weev; alphavirus) is a mosquito-borne virus that can cause severe encephalitis in humans and equids. previous studies have shown that intranasal infection of outbred cd-1 mice with the weev mcmillan (mcm) strain result in high mortality within 4 days of infection. here in vivo and ex vivo bioluminescence (blm) imaging was applied on mice intranasally infected with a recombinant mcm virus expressing firefly luciferase (fluc) to track viral neuroinvasion by fluc ... | 2013 | 23301074 |
| discovery of host-viral protein complexes during infection. | viruses have co-evolved with their hosts, developing effective approaches for hijacking and manipulating host cellular processes. therefore, for their efficient replication and spread, viruses depend on dynamic and temporally regulated interactions with host proteins. the rapid identification of host proteins targeted by viral proteins during infection provides significant insights into mechanisms of viral protein function. the resulting discoveries often lead to unique and innovative hypotheses ... | 0 | 23996249 |
| small creatures use small rnas to direct antiviral defenses. | antiviral rna silencing has been recognized as an important defense mechanism in arthropods against rna viruses. however, the role of this pathway in dna virus infection remains largely unexplored. a report in this issue of the european journal of immunology provides new insight into the role of rna silencing in antiviral defense against dna viruses. huang and zhang [eur. j. immunol. 2013. 137-146] found that the dsdna virus white spot syndrome virus, an agriculturally important pathogen of shri ... | 0 | 23322691 |
| delivery systems for gene therapy. | the structure of dna was unraveled by watson and crick in 1953, and two decades later arber, nathans and smith discovered dna restriction enzymes, which led to the rapid growth in the field of recombinant dna technology. from expressing cloned genes in bacteria to expressing foreign dna in transgenic animals, dna is now slated to be used as a therapeutic agent to replace defective genes in patients suffering from genetic disorders or to kill tumor cells in cancer patients. gene therapy provides ... | 0 | 23901186 |
| amyloid-β peptide: dr. jekyll or mr. hyde? | amyloid-β peptide (aβ) is considered a key protein in the pathogenesis of alzheimer's disease (ad) because of its neurotoxicity and capacity to form characteristic insoluble deposits known as senile plaques. aβ derives from amyloid-β protein precursor (aβpp), whose proteolytic processing generates several fragments including aβ peptides of various lengths. the normal function of aβpp and its fragments remains poorly understood. while some fragments have been suggested to have a function in norma ... | 0 | 22735675 |
| novel gene delivery systems. | gene therapy is an emerging field in medical and pharmaceutical sciences because of its potential in treating chronic diseases like cancer, viral infections, myocardial infarctions, and genetic disorders. application of gene therapy is limited because of lack of suitable methods for proper introduction of genes into cells and therefore, this is an area of interest for most of the researchers. to achieve successful gene therapy, development of proper gene delivery systems could be one of the most ... | 0 | 23799200 |
| experimental vaccines against potentially pandemic and highly pathogenic avian influenza viruses. | influenza a viruses continue to emerge and re-emerge, causing outbreaks, epidemics and occasionally pandemics. while the influenza vaccines licensed for public use are generally effective against seasonal influenza, issues arise with production, immunogenicity, and efficacy in the case of vaccines against pandemic and emerging influenza viruses, and highly pathogenic avian influenza virus in particular. thus, there is need of improved influenza vaccines and vaccination strategies. this review di ... | 0 | 23440999 |
| tinkering with translation: protein synthesis in virus-infected cells. | viruses are obligate intracellular parasites, and their replication requires host cell functions. although the size, composition, complexity, and functions encoded by their genomes are remarkably diverse, all viruses rely absolutely on the protein synthesis machinery of their host cells. lacking their own translational apparatus, they must recruit cellular ribosomes in order to translate viral mrnas and produce the protein products required for their replication. in addition, there are other con ... | 2013 | 23209131 |
| host mtorc1 signaling regulates andes virus replication. | hantavirus pulmonary syndrome (hps) is a severe respiratory disease characterized by pulmonary edema, with fatality rates of 35 to 45%. disease occurs following infection with pathogenic new world hantaviruses, such as andes virus (andv), which targets lung microvascular endothelial cells. during replication, the virus scavenges 5'-m(7)g caps from cellular mrna to ensure efficient translation of viral proteins by the host cell cap-dependent translation machinery. in cells, the mammalian target o ... | 2012 | 23135723 |
| the west nile virus capsid protein blocks apoptosis through a phosphatidylinositol 3-kinase-dependent mechanism. | west nile virus (wnv) is a mosquito-transmitted pathogen that can cause serious disease in humans. our laboratories are focused on understanding how interactions between wnv proteins and host cells contribute to virus replication and pathogenesis. wnv replication is relatively slow, and on the basis of earlier studies, the virus appears to activate survival pathways that delay host cell death during virus replication. the wnv capsid is the first viral protein produced in infected cells; however, ... | 2012 | 23115297 |
| induction of stress granule-like structures in vesicular stomatitis virus-infected cells. | previous studies from our laboratory revealed that cellular poly(c) binding protein 2 (pcbp2) downregulates vesicular stomatitis virus (vsv) gene expression. we show here that vsv infection induces the formation of granular structures in the cytoplasm containing cellular rna-binding proteins, including pcbp2, t-cell-restricted intracellular antigen 1 (tia1), and tia1-related protein (tiar). depletion of tia1 via small interfering rnas (sirnas), but not depletion of tiar, results in enhanced vsv ... | 2012 | 23077311 |
| long-distance rna-rna interactions in the coronavirus genome form high-order structures promoting discontinuous rna synthesis during transcription. | coronavirus (cov) transcription requires a high-frequency recombination process that links newly synthesized minus-strand subgenomic rna copies to the leader region, which is present only once, at the 5' end of the genome. this discontinuous rna synthesis step is based on the complementarity between the transcription-regulating sequences (trss) at the leader region and those preceding each gene in the nascent minus-strand rna. furthermore, the template switch requires the physical proximity of r ... | 2012 | 23055566 |
| enterovirus 71 uses cell surface heparan sulfate glycosaminoglycan as an attachment receptor. | enterovirus 71 (ev-71) infections are usually associated with mild hand, foot, and mouth disease in young children but have been reported to cause severe neurological complications with high mortality rates. to date, four ev-71 receptors have been identified, but inhibition of these receptors by antagonists did not completely abolish ev-71 infection, implying that there is an as yet undiscovered receptor(s). since ev-71 has a wide range of tissue tropisms, we hypothesize that ev-71 infections ma ... | 2012 | 23097443 |
| tailored hiv-1 vectors for genetic modification of primary human dendritic cells and monocytes. | monocyte-derived dendritic cells (mddcs) play a key role in the regulation of the immune system and are the target of numerous gene therapy applications. the genetic modification of mddcs is possible with human immunodeficiency virus type 1 (hiv-1)-derived lentiviral vectors (lvs) but requires high viral doses to bypass their natural resistance to viral infection, and this in turn affects their physiological properties. to date, a single viral protein is able to counter this restrictive phenotyp ... | 2012 | 23077304 |
| a novel inhibitor of dengue virus replication that targets the capsid protein. | dengue viruses (denv) infect 50 to 100 million people worldwide per year, of which 500,000 develop severe life-threatening disease. this mosquito-borne illness is endemic in most tropical and subtropical countries and has spread significantly over the last decade. while there are several promising vaccine candidates in clinical trials, there are currently no approved vaccines or therapeutics available for treatment of dengue infection. here, we describe a novel small-molecule compound, st-148, t ... | 2012 | 23070172 |
| interplay between viruses and host mrna degradation. | messenger rna degradation is a fundamental cellular process that plays a critical role in regulating gene expression by controlling both the quality and the abundance of mrnas in cells. naturally, viruses must successfully interface with the robust cellular rna degradation machinery to achieve an optimal balance between viral and cellular gene expression and establish a productive infection in the host. in the past several years, studies have discovered many elegant strategies that viruses have ... | 2012 | 23274304 |
| the folded and disordered domains of human ribosomal protein sa have both idiosyncratic and shared functions as membrane receptors. | the human rpsa [ribosomal protein sa; also known as lamr1(laminin receptor 1)] belongs to the ribosome but is also a membrane receptor for laminin, growth factors, prion, pathogens and the anticarcinogen egcg (epigallocatechin-gallate). it contributes to the crossing of the blood-brain barrier by neurotropic viruses and bacteria, and is a biomarker of metastasis. rpsa includes an n-terminal domain, which is folded and homologous to the prokaryotic rps2, and a c-terminal extension, which is intri ... | 2012 | 23137297 |
| mouse macrophage innate immune response to chikungunya virus infection. | infection with chikungunya alphavirus (chikv) can cause severe arthralgia and chronic arthritis in humans with persistence of the virus in perivascular macrophages of the synovial membrane by mechanisms largely ill-characterized. | 2012 | 23253140 |
| broad rna interference-mediated antiviral immunity and virus-specific inducible responses in drosophila. | the fruit fly drosophila melanogaster is a good model to unravel the molecular mechanisms of innate immunity and has led to some important discoveries about the sensing and signaling of microbial infections. the response of drosophila to virus infections remains poorly characterized and appears to involve two facets. on the one hand, rna interference involves the recognition and processing of dsrna into small interfering rnas by the host rnase dicer-2 (dcr-2), whereas, on the other hand, an indu ... | 2012 | 23255357 |
| macrophages, inflammation, and tumor suppressors: arf, a new player in the game. | the interaction between tumor progression and innate immune system has been well established in the last years. indeed, several lines of clinical evidence indicate that immune cells such as tumor-associated macrophages (tams) interact with tumor cells, favoring growth, angiogenesis, and metastasis of a variety of cancers. in most tumors, tams show properties of an alternative polarization phenotype (m2) characterized by the expression of a series of chemokines, cytokines, and proteases that prom ... | 2012 | 23316105 |
| inflammatory monocytes and the pathogenesis of viral encephalitis. | monocytes are a heterogeneous population of bone marrow-derived cells that are recruited to sites of infection and inflammation in many models of human diseases, including those of the central nervous system (cns). ly6chi/ccr2(hi) inflammatory monocytes have been identified as the circulating precursors of brain macrophages, dendritic cells and arguably microglia in experimental autoimmune encephalomyelitis; alzheimer's disease; stroke; and more recently in cns infection caused by herpes simplex ... | 2012 | 23244217 |
| replication of west nile virus, rabensburg lineage in mammalian cells is restricted by temperature. | the genus flavivirus currently consists of approximately 80 single-strand positive-sense rna viruses. these replicate in a range of hosts including myriad vertebrate, insect, and tick species. as a consequence of this broad host range, the majority of flaviviruses can be propagated in most vertebrate and insect cell cultures. this ability to infect arthropods and vertebrates usually is essential for maintenance of these viruses in nature. but recently, there has been the discovery of a number of ... | 2012 | 23241081 |
| proteomics-based methods for discovery, quantification, and validation of protein-protein interactions. | | 2012 | 23157382 |
| reminiscence of our research on membrane phospholipids in mammalian cells by using the novel technology. | by using "our devised up-to-the-second technique" over 30 years ago, we succeeded in the first isolation in the world of the three different kinds of mammalian cell mutants defective in the biosynthesis on each of phosphatidylserine (ps), cardiolipin (cl) and sphingomyelin (sm) from the parental cho cells. as the results, we found that during the biosyntheses of ps and sm, the biosynthetic precursor or the final lipids are transported from their synthesized intracellular organelles to the plasma ... | 0 | 23229749 |
| inhibitory effects of crude extracts from some edible thai plants against replication of hepatitis b virus and human liver cancer cells. | edible plants such as cratoxylum formosum (jack) dyer, curcumin longa lin, momordica charantia lin and moringa oleifera lam have long been believed in thai culture to relieve ulcers and the symptoms of liver disease. however, little is known about their anti-liver cancer properties and antiviral activity against hepatitis b virus (hbv). the aim of this study was to investigate the anti-liver cancer and anti-hbv activities of crude extracts from these edible plants on human liver cancer cells. | 2012 | 23216691 |
| immunization of mice with recombinant mosquito salivary protein d7 enhances mortality from subsequent west nile virus infection via mosquito bite. | mosquito salivary proteins (msps) modulate the host immune response, leading to enhancement of arboviral infections. identification of proteins in saliva responsible for immunomodulation and counteracting their effects on host immune response is a potential strategy to protect against arboviral disease. we selected a member of the d7 protein family, which are among the most abundant and immunogenic in mosquito saliva, as a vaccine candidate with the aim of neutralizing effects on the mammalian i ... | 2012 | 23236530 |
| cell-type specific requirements for thiol/disulfide exchange during hiv-1 entry and infection. | the role of disulfide bond remodeling in hiv-1 infection is well described, but the process still remains incompletely characterized. at present, the data have been predominantly obtained using established cell lines and/or cxcr4-tropic laboratory-adapted virus strains. there is also ambiguity about which disulfide isomerases/reductases play a major role in hiv-1 entry, as protein disulfide isomerase (pdi) and/or thioredoxin (trx) have emerged as the two enzymes most often implicated in this pro ... | 2012 | 23206338 |
| vesicular stomatitis virus as a flexible platform for oncolytic virotherapy against cancer. | oncolytic virus (ov) therapy is an emerging anti-cancer approach that utilizes viruses to preferentially infect and kill cancer cells, while not harming healthy cells. vesicular stomatitis virus (vsv) is a prototypic non-segmented, negative-strand rna virus with inherent ov qualities. antiviral responses induced by type i interferon pathways are believed to be impaired in most cancer cells, making them more susceptible to vsv than normal cells. several other factors make vsv a promising ov candi ... | 2012 | 23052398 |
| reemergence of chikungunya virus in cambodia. | chikungunya virus (chikv), probably asian genotype, was first detected in cambodia in 1961. despite no evidence of acute or recent chikv infections since 2000, real-time reverse transcription pcr of serum collected in 2011 detected chikv, east central south african genotype. spatiotemporal patterns and phylogenetic clustering indicate that the virus probably originated in thailand. | 0 | 23171736 |
| reverse transcription loop-mediated isothermal amplification for rapid detection of japanese encephalitis virus in swine and mosquitoes. | japanese encephalitis (je) can infect many agriculturally important animals and humans, and has a high incidence in asia. one of the natural hosts of the mosquito-borne je virus (jev) is domestic pigs, which act as amplifier hosts. porcine infection results in fatal encephalitis, abortion, and stillbirth in pregnant sows, and hypospermia in boars. in this study, a rapid jev detection method for swine and mosquitoes was developed based on reverse transcription loop-mediated isothermal amplificati ... | 2012 | 23176446 |
| rna interference as a cellular defense mechanism against the dna virus baculovirus. | in insects, the rna interference (rnai) pathway plays a major role in antiviral responses, as shown against many rna viruses. the response includes the cleavage of double-stranded rna genome or intermediates, produced during replication, into viral short interfering rnas (v-sirnas). using deep sequencing, we found that a large number of small reads of ∼20 nucleotides from helicoverpa armigera larvae infected with helicoverpa armigera single nucleopolyhedrovirus (hasnpv) were mapped to certain op ... | 2012 | 23055564 |
| gamma interferon (ifn-γ) receptor restricts systemic dengue virus replication and prevents paralysis in ifn-α/β receptor-deficient mice. | we previously reported that mice lacking alpha/beta and gamma interferon receptors (ifn-α/βr and -γr) uniformly exhibit paralysis following infection with the dengue virus (denv) clinical isolate pl046, while only a subset of mice lacking the ifn-γr alone and virtually no mice lacking the ifn-α/βr alone develop paralysis. here, using a mouse-passaged variant of pl046, strain s221, we show that in the absence of the ifn-α/βr, signaling through the ifn-γr confers approximately 140-fold greater res ... | 2012 | 22973027 |
| longitudinal analysis of the human antibody response to chikungunya virus infection: implications for serodiagnosis and vaccine development. | chikungunya virus (chikv) is an alphavirus which causes chronic and incapacitating arthralgia in humans. although previous studies have shown that antibodies against the virus are produced during and after infection, the fine specificity of the antibody response against chikv is not known. here, using plasma from patients at different times postinfection, we characterized the antibody response against various proteins of the virus. we have shown that the e2 and e3 glycoproteins and the capsid an ... | 2012 | 23015702 |
| foot-and-mouth disease virus induces autophagosomes during cell entry via a class iii phosphatidylinositol 3-kinase-independent pathway. | autophagy is an intracellular pathway that can contribute to innate antiviral immunity by delivering viruses to lysosomes for degradation or can be beneficial for viruses by providing specialized membranes for virus replication. here, we show that the picornavirus foot-and-mouth disease virus (fmdv) induces the formation of autophagosomes. induction was dependent on atg5, involved processing of lc3 to lc3ii, and led to a redistribution of lc3 from the cytosol to punctate vesicles indicative of a ... | 2012 | 22993157 |
| involvement of autophagy in coronavirus replication. | coronaviruses are single stranded, positive sense rna viruses, which induce the rearrangement of cellular membranes upon infection of a host cell. this provides the virus with a platform for the assembly of viral replication complexes, improving efficiency of rna synthesis. the membranes observed in coronavirus infected cells include double membrane vesicles. by nature of their double membrane, these vesicles resemble cellular autophagosomes, generated during the cellular autophagy pathway. in a ... | 2012 | 23202545 |
| release of dengue virus genome induced by a peptide inhibitor. | dengue virus infects approximately 100 million people annually, but there is no available therapeutic treatment. the mimetic peptide, dn59, consists of residues corresponding to the membrane interacting, amphipathic stem region of the dengue virus envelope (e) glycoprotein. this peptide is inhibitory to all four serotypes of dengue virus, as well as other flaviviruses. cryo-electron microscopy image reconstruction of dengue virus particles incubated with dn59 showed that the virus particles were ... | 2012 | 23226444 |
| il-1β signaling promotes cns-intrinsic immune control of west nile virus infection. | west nile virus (wnv) is an emerging flavivirus capable of infecting the central nervous system (cns) and mediating neuronal cell death and tissue destruction. the processes that promote inflammation and encephalitis within the cns are important for control of wnv disease but, how inflammatory signaling pathways operate to control cns infection is not defined. here, we identify il-1β signaling and the nlrp3 inflammasome as key host restriction factors involved in viral control and cns disease as ... | 2012 | 23209411 |
| complex modulation of the aedes aegypti transcriptome in response to dengue virus infection. | dengue fever is the most important arboviral disease world-wide, with aedes aegypti being the major vector. interactions between the mosquito host and dengue viruses (denv) are complex and vector competence varies among geographically-distinct ae. aegypti populations. additionally, dengue is caused by four antigenically-distinct viral serotypes (denv1-4), each with multiple genotypes. each virus genotype interacts differently with vertebrate and invertebrate hosts. analyses of alterations in mos ... | 2012 | 23209765 |
| genotypic and phenotypic characterization of chikungunya virus of different genotypes from malaysia. | mosquito-borne chikungunya virus (chikv) has recently re-emerged globally. the epidemic east/central/south african (ecsa) strains have spread for the first time to asia, which previously only had endemic asian strains. in malaysia, the ecsa strain caused an extensive nationwide outbreak in 2008, while the asian strains only caused limited outbreaks prior to this. to gain insight into these observed epidemiological differences, we compared genotypic and phenotypic characteristics of chikv of asia ... | 2012 | 23209750 |
| host cell factors in filovirus entry: novel players, new insights. | filoviruses cause severe hemorrhagic fever in humans with high case-fatality rates. the cellular factors exploited by filoviruses for their spread constitute potential targets for intervention, but are incompletely defined. the viral glycoprotein (gp) mediates filovirus entry into host cells. recent studies revealed important insights into the host cell molecules engaged by gp for cellular entry. the binding of gp to cellular lectins was found to concentrate virions onto susceptible cells and mi ... | 0 | 23342362 |
| infection by chikungunya virus modulates the expression of several proteins in aedes aegypti salivary glands. | arthropod-borne viral infections cause several emerging and resurging infectious diseases. among the diseases caused by arboviruses, chikungunya is responsible for a high level of severe human disease worldwide. the salivary glands of mosquitoes are the last barrier before pathogen transmission. | 2012 | 23153178 |
| demographic consequences of predators on prey: trait and density mediated effects on mosquito larvae in containers. | predators may affect prey population growth and community diversity through density mediated lethal and trait mediated non-lethal effects that influence phenotypic traits of prey. we tested experimentally the roles of thinning the density of prey (lethality) in the absence of predator cues and density and trait mediated effects (lethality + intimidation) of predatory midge corethrella appendiculata on competing native and invasive mosquito prey. predator-mediated reductions in prey and density r ... | 2012 | 23152748 |
| modulation of hepatitis c virus rna abundance and virus release by dispersion of processing bodies and enrichment of stress granules. | components of cytoplasmic processing bodies (p-bodies) and stress granules can be subverted during viral infections to modulate viral gene expression. because hepatitis c virus (hcv) rna abundance is regulated by p-body components such as microrna mir-122, argonaute 2 and rna helicase rck/p54, we examined whether hcv infection modulates p-bodies and stress granules during viral infection. it was discovered that hcv infection decreased the number of p-bodies, but induced the formation of stress g ... | 2012 | 23141719 |
| dendritic cell-directed vaccination with a lentivector encoding psca for prostate cancer in mice. | many studies have demonstrated that prostate stem cell antigen (psca) is an attractive target for immunotherapy based on its overexpression in prostate tumor tissue, especially in some metastatic tissues. in this study, we evaluated dendritic cell (dc)-directed lentiviral vector (dclv) encoding murine psca (dclv-psca) as a novel tumor vaccine for prostate cancer in mouse models. we showed that dclv-psca could preferentially deliver the psca antigen gene to dc-sign-expressing 293t cells and bone ... | 2012 | 23139820 |
| apoptosis in mosquito salivary glands: sindbis virus-associated and tissue homeostasis. | apoptosis is observed during a spectrum of conditions including exogenous virus infection and endogenous cellular turnover. adult female aedes albopictus mosquitoes challenged with increasing titres of sindbis virus (sinv) via intrathoracic inoculation demonstrated that the injection dosage did not result in significantly different levels of virus growth or mosquito survival at day 10 post-infection. tissues probed for apoptosis using an in situ tunel assay revealed sinv-associated apoptotic cel ... | 2012 | 22894924 |
| structural and dynamic determinants of type i interferon receptor assembly and their functional interpretation. | type i interferons (ifns) form a network of homologous cytokines that bind to a shared, heterodimeric cell surface receptor and engage signaling pathways that activate innate and adaptive immune responses. the ability of ifns to mediate differential responses through the same cell surface receptor has been subject of a controversial debate and has important medical implications. during the past decade, a comprehensive insight into the structure, energetics, and dynamics of ifn recognition by its ... | 0 | 23046138 |
| gene expression studies of host response to salmonid alphavirus subtype 3 experimental infections in atlantic salmon. | salmonid alphavirus subtype-3 (sav-3) infection in atlantic salmon is exclusively found in norway. the salmonid alphaviruses have been well characterized at the genome level but there is limited information about the host-pathogen interaction phenomena. this study was undertaken to characterize the replication and spread of sav-3 in internal organs of experimentally infected atlantic salmon and the subsequent innate and adaptive immune responses. in addition, suitability of a cohabitation challe ... | 2012 | 23116479 |
| zinc finger antiviral protein inhibits murine gammaherpesvirus 68 m2 expression and regulates viral latency in cultured cells. | zinc finger antiviral protein (zap) is a host factor that specifically inhibits the replication of certain viruses by binding to specific viral mrnas and repressing mrna expression. here we report that zap inhibits expression of murine gammaherpesvirus 68 (mhv-68) m2, which plays important roles in establishment and maintenance of viral latency. downregulation of endogenous zap in cells harboring latent mhv-68 promoted lytic replication of the virus. these results suggest that zap inhibits m2 ex ... | 2012 | 22951821 |
| autophagy as a stress-response and quality-control mechanism: implications for cell injury and human disease. | autophagy, a vital catabolic process that degrades cytoplasmic components within the lysosome, is an essential cytoprotective response to pathologic stresses that occur during diseases such as cancer, ischemia, and infection. in addition to its role as a stress-response pathway, autophagy plays an essential quality-control function in the cell by promoting basal turnover of long-lived proteins and organelles, as well as by selectively degrading damaged cellular components. this homeostatic funct ... | 2012 | 23072311 |
| making connections in insect innate immunity. | | 2012 | 23100537 |
| transient activation of the pi3k-akt pathway by hepatitis c virus to enhance viral entry. | the pi3k-akt signaling pathway plays an important role in cell growth and metabolism. here we report that hepatitis c virus (hcv) transiently activates the pi3k-akt pathway. this activation was observed as early as 15 min postinfection, peaked by 30 min, and became undetectable at 24 h postinfection. the activation of akt could also be mediated by uv-inactivated hcv, hcv pseudoparticle, and the ectodomain of the hcv e2 envelope protein. because antibodies directed against cd81 and claudin-1, but ... | 2012 | 23095753 |
| autophagy protects against active tuberculosis by suppressing bacterial burden and inflammation. | autophagy is a cell biological pathway affecting immune responses. in vitro, autophagy acts as a cell-autonomous defense against mycobacterium tuberculosis, but its role in vivo is unknown. here we show that autophagy plays a dual role against tuberculosis: antibacterial and anti-inflammatory. m. tuberculosis infection of atg5(fl/fl) lysm-cre(+) mice relative to autophagy-proficient littermates resulted in increased bacillary burden and excessive pulmonary inflammation characterized by neutrophi ... | 2012 | 23093667 |
| in vivo gene transfer targeting in pancreatic adenocarcinoma with cell surface antigens. | pancreatic ductal adenocarcinoma is a deadly malignancy resistant to current therapies. it is critical to test new strategies, including tumor-targeted delivery of therapeutic agents. this study tested the possibility to target the transfer of a suicide gene in tumor cells using an oncotropic lentiviral vector. | 2012 | 23088623 |
| coordinate action of pre- and postsynaptic brain-derived neurotrophic factor is required for ampar trafficking and acquisition of in vitro classical conditioning. | brain-derived neurotrophic factor (bdnf) has been implicated in mechanisms of synaptic plasticity such as long-term potentiation (ltp), but its role in associative learning remains largely unknown. in the present study, we investigated the function of bdnf and its receptor tropomyosin-related kinase b (trkb) in an in vitro model of classical conditioning using pond turtles, pseudemys scripta elegans. conditioning resulted in a significant increase in bdnf and phospho (p)-trk expression. bath app ... | 2008 | 18639615 |
| neuroimmunology of central nervous system viral infections: the cells, molecules and mechanisms involved. | viral infections of the central nervous system (cns) necessitate rapid, yet tightly controlled responses to contain viral spread while limiting tissue damage. all cns resident cell types are equipped with pattern recognition receptors (prrs) to respond to viruses. the resulting activation of ifn-alpha/beta, pro-inflammatory cytokines and chemokines is dependent on the virus replication strategy, tropism and prr distribution. although ifn-alpha/beta induced antiviral mediators are essential to re ... | 2008 | 18562249 |
| comparison of slow and fast neocortical neuron migration using a new in vitro model. | mutations, toxic insults and radiation exposure are known to slow or arrest the migration of cortical neurons, in most cases by unknown mechanisms. the movement of migrating neurons is saltatory, reflecting the intermittent movement of the nucleus (nucleokinesis) within the confines of the plasma membrane. each nucleokinetic movement is analogous to a step. thus, average migration speed could be reduced by lowering step frequency and/or step distance. | 2008 | 18534012 |
| complex responses to a diverse environment. | a report on the keystone symposium 'innate immunity: signaling mechanisms', keystone, usa, 24-29 february, 2008. | 2008 | 18533049 |
| bcl-2 family members: dual regulators of apoptosis and autophagy. | the essential autophagy protein and haplo-insufficient tumor suppressor, beclin 1, interacts with several cofactors (ambra1, bif-1, uvrag) to activate the lipid kinase vps34, thereby inducing autophagy. in normal conditions, beclin 1 is bound to and inhibited by bcl-2 or the bcl-2 homolog bcl-x(l). this interaction involves a bcl-2 homology 3 (bh3) domain in beclin 1 and the bh3 binding groove of bcl-2/bcl-x(l). other proteins containing bh3 domains, called bh3-only proteins, can competitively d ... | 2008 | 18497563 |
| a transgenic sensor strain for monitoring the rnai pathway in the yellow fever mosquito, aedes aegypti. | the rna interference pathway functions as an antiviral defense in invertebrates. in order to generate a phenotypic marker which "senses" the status of the rnai pathway in aedes aegypti, transgenic strains were developed to express egfp and dsred marker genes in the eye, as well as double-stranded rna homologous to a portion of the egfp gene. transgenic "sensor" mosquitoes exhibited robust eye-specific dsred expression with little egfp, indicating rnai-based silencing. cloning and high-throughput ... | 2008 | 18549956 |
| p bodies, stress granules, and viral life cycles. | eukaryotic mrnas are in a dynamic equilibrium between different subcellular locations. translating mrnas can be found in polysomes, mrnas stalled in translation initiation accumulate in stress granules and mrnas targeted for degradation or translation repression can accumulate in p bodies. partitioning of mrnas between polysomes, stress granules, and p bodies affects rates of translation and mrna degradation. host proteins within p bodies and stress granules can enhance or limit viral infection, ... | 0 | 18407064 |
| bhlh-pas family transcription factor methoprene-tolerant plays a key role in jh action in preventing the premature development of adult structures during larval-pupal metamorphosis. | the biological actions of juvenile hormones are well studied; they regulate almost all aspects of an insect's life. however, the molecular actions of these hormones are not well understood. recent studies in the red flour beetle, tribolium castaneum, demonstrated the utility of this insect as a model system to study jh action. these studies confirmed that the bhlh-pas family transcription factor, methoprene-tolerant (tcmet,) plays a key role in jh action during larval stages. in this study, we i ... | 2008 | 18450431 |
| can essential fatty acids reduce the burden of disease(s)? | coronary heart disease, stroke, diabetes mellitus, hypertension, cancer, depression schizophrenia, alzheimer's disease, and collagen vascular diseases are low-grade systemic inflammatory conditions that are a severe burden on health care resources. essential fatty acids (efas) and their metabolites: eicosapentaenoic acid (epa), docosahexaenoic acid (dha), gamma-linolenic acid (gla), dihomo-gamma-linolenic acid (dgla), and arachidonic acid (aa) and their products: prostaglandin e1, prostacyclin, ... | 2008 | 18348729 |
| p72 dead box rna helicase is required for optimal function of the zinc-finger antiviral protein. | the zinc-finger antiviral protein (zap) specifically inhibits the replication of many viruses by preventing the accumulation of viral mrnas in the cytoplasm. zap directly binds to the viral mrnas and recruits the rna exosome to degrade the target rna. in the present study, we identified the p72 dead box rna helicase, but not the highly similar rna helicase p68, as a zap-interacting protein. the binding domain of zap was mapped to its n-terminal portion, whereas both the n- and c-terminal domains ... | 2008 | 18334637 |
| recycle or die: the role of autophagy in cardioprotection. | autophagy is a highly conserved cellular process responsible for the degradation of long-lived proteins and organelles. autophagy occurs at low levels under normal conditions, but is upregulated in response to stress such as nutrient deprivation, hypoxia, mitochondrial dysfunction, and infection. upregulation of autophagy may be beneficial to the cell by recycling of proteins to generate free amino acids and fatty acids needed to maintain energy production, by removing damaged organelles, and by ... | 2008 | 18353358 |
| identification of a coronavirus transcription enhancer. | coronavirus (cov) transcription includes a discontinuous mechanism during the synthesis of sub-genome-length minus-strand rnas leading to a collection of mrnas in which the 5' terminal leader sequence is fused to contiguous genome sequences. it has been previously shown that transcription-regulating sequences (trss) preceding each gene regulate transcription. base pairing between the leader trs (trs-l) and the complement of the body trs (ctrs-b) in the nascent rna is a determinant factor during ... | 2008 | 18272586 |
| autophagy and antiviral immunity. | autophagy is an ancient pathway designed to maintain cellular homeostasis by degrading long-lived proteins and organelles in the cytosol. recent studies demonstrate that autophagy is utilized by the cells of the innate and adaptive immune systems to combat viral infections. autophagy plays a key role in recognizing signatures of viral infection, and represents a critical effector mechanism to restrict viral replication. on the other hand, autophagosomes have been exploited by certain viruses as ... | 2008 | 18262399 |
| exploring systemic rna interference in insects: a genome-wide survey for rnai genes in tribolium. | rna interference (rnai) is a highly conserved cellular mechanism. in some organisms, such as caenorhabditis elegans, the rnai response can be transmitted systemically. some insects also exhibit a systemic rnai response. however, drosophila, the leading insect model organism, does not show a robust systemic rnai response, necessitating another model system to study the molecular mechanism of systemic rnai in insects. | 2008 | 18201385 |
| viral and developmental cell fusion mechanisms: conservation and divergence. | membrane fusion is a fundamental requirement in numerous developmental, physiological, and pathological processes in eukaryotes. so far, only a limited number of viral and cellular fusogens, proteins that fuse membranes, have been isolated and characterized. despite the diversity in structures and functions of known fusogens, some common principles of action apply to all fusion reactions. these can serve as guidelines in the search for new fusogens, and may allow the formulation of a cross-speci ... | 0 | 18194649 |
| tyrosine phosphorylation regulates nuclear translocation of pkcdelta. | pkcdelta is essential for apoptosis, but regulation of the proapoptotic function of this ubiquitous kinase is not well understood. nuclear translocation of pkcdelta is necessary and sufficient to induce apoptosis and is mediated via a c-terminal bipartite nuclear localization sequence. however, pkcdelta is found predominantly in the cytoplasm of nonapoptotic cells, and the apoptotic signal that activates its nuclear translocation is not known. we show that in salivary epithelial cells, phosphory ... | 2007 | 18059334 |
| rapidly inducible, genetically targeted inactivation of neural and synaptic activity in vivo. | inducible and reversible perturbation of the activity of selected neurons in vivo is critical to understanding the dynamics of brain circuits. several genetically encoded systems for rapid inducible neuronal silencing have been developed in the past few years offering an arsenal of tools for in vivo experiments. some systems are based on ion-channels or pumps, others on g protein coupled receptors, and yet others on modified presynaptic proteins. inducers range from light to small molecules to p ... | 2007 | 18054219 |
| flock house virus induces apoptosis by depletion of drosophila inhibitor-of-apoptosis protein diap1. | the molecular mechanisms by which rna viruses induce apoptosis and apoptosis-associated pathology are not fully understood. here we show that flock house virus (fhv), one of the simplest rna viruses (family, nodaviridae), induces robust apoptosis of permissive drosophila line-1 (dl-1) cells. to define the pathway by which fhv triggers apoptosis in this model invertebrate system, we investigated the potential role of drosophila apoptotic effectors during infection. suggesting the involvement of h ... | 2007 | 17989181 |
| cytopathogenesis and inhibition of host gene expression by rna viruses. | many viruses interfere with host cell function in ways that are harmful or pathological. this often results in changes in cell morphology referred to as cytopathic effects. however, pathogenesis of virus infections also involves inhibition of host cell gene expression. thus the term "cytopathogenesis," or pathogenesis at the cellular level, is meant to be broader than the term "cytopathic effects" and includes other cellular changes that contribute to viral pathogenesis in addition to those chan ... | 0 | 11104816 |
| role of antibodies in controlling viral disease: lessons from experiments of nature and gene knockouts. | | 0 | 11024107 |
| epidermal growth factor and membrane trafficking. egf receptor activation of endocytosis requires rab5a. | activated epidermal growth factor receptors recruit various intracellular proteins leading to signal generation and endocytic trafficking. although activated receptors are rapidly internalized into the endocytic compartment and subsequently degraded in lysosomes, the linkage between signaling and endocytosis is not well understood. here we show that egf stimulation of nr6 cells induces a specific, rapid and transient activation of rab5a. egf also enhanced translocation of the rab5 effector, earl ... | 0 | 11062256 |
| leader proteinase of the beet yellows closterovirus: mutation analysis of the function in genome amplification. | the beet yellows closterovirus leader proteinase (l-pro) possesses a c-terminal proteinase domain and a nonproteolytic n-terminal domain. it was found that although l-pro is not essential for basal-level replication, deletion of its n-terminal domain resulted in a 1, 000-fold reduction in rna accumulation. mutagenic analysis of the n-terminal domain revealed its structural flexibility except for the 54-codon-long, 5'-terminal element in the corresponding open reading frame that is critical for e ... | 0 | 11000252 |
| essential and dispensable virus-encoded replication elements revealed by efforts to develop hypoviruses as gene expression vectors. | we have investigated whether hypoviruses, viral agents responsible for virulence attenuation (hypovirulence) of the chestnut blight fungus cryphonectria parasitica, could serve as gene expression vectors. the infectious cdna clone of the prototypic hypovirus chv1-ep713 was modified to generate 20 different vector candidates. although transient expression was achieved for a subset of vectors that contained the green fluorescent protein gene from aequorea victoria, long-term expression (past day 8 ... | 0 | 10906211 |
| translational control of viral gene expression in eukaryotes. | as obligate intracellular parasites, viruses rely exclusively on the translational machinery of the host cell for the synthesis of viral proteins. this relationship has imposed numerous challenges on both the infecting virus and the host cell. importantly, viruses must compete with the endogenous transcripts of the host cell for the translation of viral mrna. eukaryotic viruses have thus evolved diverse mechanisms to ensure translational efficiency of viral mrna above and beyond that of cellular ... | 0 | 10839817 |
| the inhibitors of protein acylation, cerulenin and tunicamycin, increase voltage-dependent ca(2+) currents in the insulin-secreting ins 832/13 cell. | as it has been suggested that protein acylation plays a role in nutrient stimulus-secretion coupling in the pancreatic beta-cell, we examined the insulin-secreting ins 832/13 beta-cell line for evidence that protein acylation was involved. the perforated whole-cell configuration was employed to voltage-clamp ins 832/13 cells. voltage pulses were applied and ca(2+) currents measured in the presence and absence of the protein acylation inhibitors cerulenin and tunicamycin. both inhibitors enhanced ... | 2007 | 17548064 |
| tyrosine 311 is phosphorylated by c-abl and promotes the apoptotic effect of pkcdelta in glioma cells. | in this study we characterized the phosphorylation of tyrosine 311 and its role in the apoptotic function of pkcdelta in glioma cells. we found that c-abl phosphorylated pkcdelta on tyrosine 311 in response to h2o2 and that this phosphorylation contributed to the apoptotic effect of h2o2. in contrast, src, lyn, and yes were not involved in the phosphorylation of tyrosine 311 by h2o2. a phosphomimetic pkcdelta mutant, in which tyrosine 311 was mutated to glutamic acid (pkcdeltay311e), induced a l ... | 2006 | 17126298 |
| distinguishing reversible from irreversible virus capsid assembly. | capsids of spherical viruses may be constructed from hundreds or thousands of copies of the major capsid protein(s). these assembly reactions are poorly understood. here we consider the predicted behavior for assembly where the component reactions have weak association energy and are reversible and compare them to essentially irreversible reactions. the comparisons are based on mass action calculations and the behavior predicted from kinetic simulations where assembly is described as a cascade o ... | 2006 | 17157314 |
| functional role of aspartic proteinase cathepsin d in insect metamorphosis. | metamorphosis is a complex, highly conserved and strictly regulated development process that involves the programmed cell death of obsolete larval organs. here we show a novel functional role for the aspartic proteinase cathepsin d during insect metamorphosis. | 2006 | 17062167 |