PMID(sorted descending)
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 ...201223116479
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, ...201223115297
gcn2 has inhibitory effect on human immunodeficiency virus-1 protein synthesis and is cleaved upon viral infection.the reversible phosphorylation of the alpha-subunit of eukaryotic translation initiation factor 2 (eif2alpha) is a well-characterized mechanism of translational control in response to a wide variety of cellular stresses, including viral infection. beside pkr, the eif2alpha kinase gcn2 participates in the cellular response against viral infection by rna viruses with central nervous system tropism. pkr has also been involved in the antiviral response against hiv-1, although this antiviral effect i ...201223110064
making connections in insect innate immunity. 201223100537
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 ...201223097443
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 ...201223095753
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 ...201223093667
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.201223088623
sequestration of g3bp coupled with efficient translation inhibits stress granules in semliki forest virus infection.dynamic, mrna-containing stress granules (sgs) form in the cytoplasm of cells under environmental stresses, including viral infection. many viruses appear to employ mechanisms to disrupt the formation of sgs on their mrnas, suggesting that they represent a cellular defense against infection. here, we report that early in semliki forest virus infection, the c-terminal domain of the viral nonstructural protein 3 (nsp3) forms a complex with ras-gap sh3-domain-binding protein (g3bp) and sequesters i ...201223087212
transcriptional pausing controls a rapid antiviral innate immune response in drosophila.innate immune responses are characterized by precise gene expression whereby gene subsets are temporally induced to limit infection, although the mechanisms involved are incompletely understood. we show that antiviral immunity in drosophila requires the transcriptional pausing pathway, including negative elongation factor (nelf) that pauses rna polymerase ii (pol ii) and positive elongation factor b (p-tefb), which releases paused pol ii to produce full-length transcripts. we identify a set of g ...023084920
an attenuating mutation in a neurovirulent sindbis virus strain interacts with the ips-1 signaling pathway in vivo.the ar86 strain of sindbis virus causes lethal neurologic disease in adult mice. previous studies have identified a virulence determinant at nonstructural protein (nsp) 1 position 538 that regulates neurovirulence, modulates clearance from the cns, and interferes with the type i interferon pathway. the studies herein demonstrate that in the absence of type i interferon signaling, the attenuated mutant exhibited equivalent virulence to s300 virus. furthermore, both s300 and nsp1 t538i viruses dis ...201223084425
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 ...201223077311
attenuation of semliki forest virus neurovirulence by microrna-mediated detargeting.artificial target sequences for tissue-specific mirnas have recently been introduced as a new means for altering the tissue tropism of viral replication. this approach can be used to improve the safety of oncolytic viruses for cancer virotherapy by restricting their replication in unwanted tissues, such as the liver. semliki forest virus (sfv) is a positive-strand rna virus and, similar to the related alphaviruses, like sindbis virus, has potential as a gene therapy vector and an oncolytic virot ...201223077310
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 ...201223077304
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 ...201323072320
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 ...201223072311
pathogenic characterization of a cervical lymph node derived from a patient with kawasaki disease.kawasaki disease (kd) is the most common cause of multisystem vasculitis in childhood. although cervical lymphadenitis is one of the major symptoms in kd, lymph node biopsy is rarely performed, because kd is usually diagnosed by clinical symptoms. a cervical lymph node biopsy was taken from a girl aged 1 year and 8 months who had suspected lymphoma, but she was diagnosed with kd after the biopsy. the cervical lymph node specimen was analyzed with multivirus real-time pcr that can detect >160 vir ...201223071864
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 ...201223070172
expression of plasmid-based shrna against the e1 and nsp1 genes effectively silenced chikungunya virus replication.chikungunya virus (chikv) is a re-emerging alphavirus that causes chikungunya fever and persistent arthralgia in humans. currently, there is no effective vaccine or antiviral against chikv infection. therefore, this study evaluates whether rna interference which targets at viral genomic level may be a novel antiviral strategy to inhibit the medically important chikv infection.201223056297
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 ...201223055566
rna interference as a cellular defense mechanism against the dna virus 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 ...201223055564
dynamic regulation of synaptic maturation state by voltage-gated a-type k+ channels in ca1 hippocampal pyramidal neurons.neuronal activity is critical for the formation and modification of neural circuits during brain development. in hippocampal ca1 pyramidal dendrites, a-type voltage-gated k(+) currents, formed primarily by kv4.2 subunits, control excitability. here we used kv4.2 knock-out (kv4.2-ko) mice along with acute in vivo expression of kv4.2 or its dominant-negative pore mutant to examine the role of kv4.2 in the development of ca1 synapses. we found that kv4.2 expression induces synaptic maturation in ju ...023055512
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 ...201223052398
intrahepatic infiltrating nk and cd8 t cells cause liver cell death in different phases of dengue virus infection.elevated liver enzyme level is an outstanding feature in patients with dengue. however, the pathogenic mechanism of liver injury has not been clearly demonstrated. in this study, employing a mouse model we aimed to investigate the immunopathogenic mechanism of dengue liver injury. immunocompetent c57bl/6 mice were infected intravenously with dengue virus strain 16681. infected mice had transient viremia, detectable viral capsid gene and cleaved caspase 3 in the liver. in the mean time, nk cell a ...201223050007
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 ...023046138
vipr hmm: a hidden markov model for detecting recombination with microbial detection microarrays.current methods in diagnostic microbiology typically focus on the detection of a single genomic locus or protein in a candidate agent. the presence of the entire microbe is then inferred from this isolated result. problematically, the presence of recombination in microbial genomes would go undetected unless other genomic loci or protein components were specifically assayed. microarrays lend themselves well to the detection of multiple loci from a given microbe; furthermore, the inherent nature o ...201223044542
autophagy and selective deployment of atg proteins in antiviral defense.autophagy is an evolutionarily ancient process eukaryotic cells utilize to remove and recycle intracellular material in order to maintain cellular homeostasis. in metazoans, the autophagy machinery not only functions in this capacity but also has evolved to perform a diverse repertoire of intracellular transport and regulatory functions. in response to virus infections, the autophagy machinery degrades viruses, shuttles viral pathogen-associated molecular patterns to endosomes containing toll-li ...201223042773
67 kda laminin receptor: structure, function and role in cancer and infection.the 67 kda high affinity laminin receptor (67lr) is a non integrin cell surface receptor for the extracellular matrix whose expression is increased in neoplastic cells and directly correlates with an enhanced invasive and metastatic potential. 67lr derives from homo- or hetero-dimerization of a 37 kda cytosolic precursor (37lrp), by fatty acid acylation. interestingly, 37lrp is a multifunctional protein involved in the translational machinery and has also been found in the nucleus, where it is t ...201223042000
the alphavirus e3 glycoprotein functions in a clade-specific manner.the 80 trimeric, glycoprotein spikes that cover the surface of alphavirus particles are required for mediating viral entry into a host cell. spike assembly is a regulated process that requires interactions between five structural proteins, e3, e2, 6k and its translational frameshift product tf, and e1. e3 is a small, ∼65-amino-acid glycoprotein that has two known functions: e3 serves as the signal sequence for translocation of the e3-e2-6k-e1 polyprotein into the endoplasmic reticulum (er), and ...201223035234
role of bunyamwera orthobunyavirus nss protein in infection of mosquito cells.bunyamwera orthobunyavirus is both the prototype and study model of the bunyaviridae family. the viral nss protein seems to contribute to the different outcomes of infection in mammalian and mosquito cell lines. however, only limited information is available on the growth of bunyamwera virus in cultured mosquito cells other than the aedes albopictus c6/36 line.201223029584
west nile virus (wnv) replication is independent of autophagy in mammalian cells.autophagy is a homeostatic process responsible for recycling cytosolic proteins and organelles. moreover, this pathway contributes to the cell's intrinsic innate defenses. while many viruses have evolved mechanisms to antagonize the antiviral effects of the autophagy pathway, others subvert autophagy to facilitate replication. here, we have investigated the role of autophagy in west nile virus (wnv) replication. experiments in cell lines derived from a variety of sources, including the kidney, l ...201223029249
activity based protein profiling to detect serine hydrolase alterations in virus infected cells.activity-based protein profiling (abpp) is a newly emerging technique that uses active site-directed probes to monitor the functional status of enzymes. serine hydrolases are one of the largest families of enzymes in mammals. more than 200 serine hydrolases have been identified, but little is known about their specific roles. serine hydrolases are involved in a variety of physiological functions, including digestion, immune response, blood coagulation, and reproduction. abpp has been used recent ...201223024641
translational repression precedes and is required for zap-mediated mrna decay.translational repression and mrna degradation are two major mechanisms for post-transcriptional regulation of gene expression. the detailed relationship between these two processes is not yet well established. zinc-finger antiviral protein (zap) inhibits the replication of certain viruses, including human immunodeficiency virus 1, by binding directly to specific viral mrnas and recruiting cellular mrna degradation machinery to degrade the target mrna. here, we report that zap also inhibits the t ...201223023399
replication of respiratory syncytial virus is inhibited by the host defense molecule viperin.respiratory syncytial virus (rsv) is an important viral pathogen of otitis media, bronchiolitis, and pneumonia. as infection of the upper airways is a precondition for the development of these diseases, understanding rsv pathogenesis and the host response induced by rsv in this niche may enable the development of novel therapeutic strategies against this virus. we have used a microarray approach and showed that expression of the gene that encodes the antiviral protein viperin was significantly u ...201223018837
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 ...201223015702
structural and functional insights into alphavirus polyprotein processing and pathogenesis.alphaviruses, a group of positive-sense rna viruses, are globally distributed arboviruses capable of causing rash, arthritis, encephalitis, and death in humans. the viral replication machinery consists of four nonstructural proteins (nsp1-4) produced as a single polyprotein. processing of the polyprotein occurs in a highly regulated manner, with cleavage at the p2/3 junction influencing rna template use during genome replication. here, we report the structure of p23 in a precleavage form. the pr ...201223010928
living on the edge with too many mouths to feed: why dopamine neurons die.although genes, protein aggregates, environmental toxins, and other factors associated with parkinson's disease (pd) are widely distributed in the nervous system and affect many classes of neurons, a consistent feature of pd is the exceptional and selective vulnerability of dopamine (da) neurons of the snc. what is it about these neurons, among all other neurons in the brain, that makes them so susceptible in pd? we hypothesize that a major contributory factor is the unique cellular architecture ...201223008164
[preparation and identification of a recombinant hepatitis c virus (hcv) based on sindbis virus vector].to construct the recombinant virus-like particles containing hcv envelope glycoprotein e1e2 based on sindbis virus vector.201223002557
a virological view of innate immune recognition.the innate immune system uses multiple strategies to detect viral infections. because all viruses rely on host cells for their synthesis and propagation, the molecular features used to detect viral infections must be unique to viruses and absent from host cells. research in the past decade has advanced our understanding of various cell-intrinsic and cell-extrinsic modes of virus recognition. this review examines the innate recognition from the point of view of virus invasion and replication stra ...022994491
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 ...201222993157
everybody wins! poland hosts thrilling competitions of viruses, rnai and football teams.the esf-embo conference on 'antiviral rnai: from molecular biology towards applications' took place in june 2012 in pultusk, poland. it brought together scientists working at the interface of rnai and virus infections in different organisms, covering the complete range from basic mechanisms of rna silencing to rnai-based antiviral therapy.201222986551
targeting lentiviral vectors for cancer of tumour-associated antigens (taa) in a way that induces effective, specific immunity is a challenge in anti-cancer vaccine design. circumventing tumour-induced tolerogenic mechanisms in vivo is also critical for effective immunotherapy. effective immune responses are induced by professional antigen presenting cells, in particular dendritic cells (dc). this requires presentation of the antigen to both cd4(+) and cd8(+) t cells in the context of strong co-stimulatory signals. lentiviral ...201122983382
a neuron-specific role for autophagy in antiviral defense against herpes simplex virus.type i interferons (ifns) are considered to be the universal mechanism by which viral infections are controlled. however, many ifn-stimulated genes (isgs) rely on antiviral pathways that are toxic to host cells, which may be detrimental in nonrenewable cell types, such as neurons. we show that dorsal root ganglionic (drg) neurons produced little type i ifns in response to infection with a neurotropic virus, herpes simplex type 1 (hsv-1). further, type i ifn treatment failed to completely block h ...022980330
preparation of bioactive interferon alpha-loaded polysaccharide nanoparticles using a new approach of temperature-induced water phase/water-phase emulsion.the aim of this study was to develop a temperature-induced polyethylene glycol (peg) water phase/polysaccharide water-phase emulsion approach for preparing interferon alpha-2b (ifnα-2b)-loaded polysaccharide nanoparticles. ifnα-2b was first added to a mixture of an aqueous solution of peg and polysaccharide. the mixture solution was stirred in a magnetic stirrer at a rate of 2000 rpm for 45 seconds at 0°c ± 0.5°c. the solution was then prefrozen at different temperatures. the polysaccharide and ...201222973103
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 ...201222973027
nationwide inventory of mosquito biodiversity (diptera: culicidae) in belgium, 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 ...201222971463
effects of larval rearing temperature on immature development and west nile virus vector competence of culex tarsalis.temperature is known to induce changes in mosquito physiology, development, ecology, and in some species, vector competence for arboviruses. since colonized mosquitoes are reared under laboratory conditions that can be significantly different from their field counterparts, laboratory vector competence experiments may not accurately reflect natural vector-virus interactions.201222967798
phenotypic and molecular characteristics of plaque-purified mx10 virus, an oriental-australian genotype of sindbis virus from yunnan, china.a previous investigation showed that mx10 virus, recently isolated in china, belongs to the oriental-australian (o/a) genotype of sindbis virus (sinv) (wang jinglin, 2011, atmh). similar to the mre16 isolate, the prototype o/a genotype of sinv, two derivate viruses with obviously different plaque morphologies were derived from mx10 virus, which were accordingly denoted as mx10-lp and mx10-sp. mx10-lp virus exhibited higher neurovirulence in neonatal mice than mx10-sp virus. analysis of the compl ...201322965578
overexpression of membrane proteins in mammalian cells for structural studies.the number of structures of integral membrane proteins from higher eukaryotes is steadily increasing due to a number of innovative protein engineering and crystallization strategies devised over the last few years. however, it is sobering to reflect that these structures represent only a tiny proportion of the total number of membrane proteins encoded by a mammalian genome. in addition, the structures determined to date are of the most tractable membrane proteins, i.e., those that are expressed ...201222963530
mosquito vectors survey in the al-ahsaa district of eastern saudi arabia.the present study aimed to identify the mosquito vectors distributed throughout al-ahsaa district situated in the eastern region of saudi arabia. mosquito larvae were collected seasonally for one year (october 2009 to september 2010) from different breeding sites in seven rural areas utilizing long aquatic nets. salinity and ph of these breeding sites were also measured seasonally. the survey revealed the presence of five mosquito species, aedes caspius pallas (diptera: culicidae), anopheles mul ...201122958070
sindbis viral vectors target hematopoietic malignant cells.sindbis viral vectors target and inhibit the growth of various solid tumors in mouse models. however, their efficacy against blood cancer has not been well established. here, we show that sindbis vectors infect and efficiently trigger apoptosis in mouse bw5147 malignant hematopoietic t-cells, but only at low levels in human lymphoma and leukemia cells (jurkat, karpas, cem, dhl and jb). the mr 37/67 kd laminin receptor (lamr) has been suggested to be the receptor for sindbis virus. however, jb ce ...201222956041
probing the early temporal and spatial interaction of the sindbis virus capsid and e2 proteins with reverse genetics.a 7-å cryoelectron microscopy-based reconstruction of sindbis virus (sinv) was recently generated. fitting the crystal structure of the sinv capsid protein (cp) into the density map revealed that the f2-g2 loop of the cp was shifted away from cytoplasmic domain of e2 (cde2) in the 7-å reconstruction relative to its position in the cp crystal structure. furthermore, the reconstruction demonstrated that residue e395 in region i of the cytoplasmic domain of the e2 envelope protein (cde2-ri) and k25 ...201222951842
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 ...201222951821
mitophagy: mechanisms, pathophysiological roles, and analysis.abstract mitochondria are essential organelles that regulate cellular energy homeostasis and cell death. the removal of damaged mitochondria through autophagy, a process called mitophagy, is thus critical for maintaining proper cellular functions. indeed, mitophagy has been recently proposed to play critical roles in terminal differentiation of red blood cells, paternal mitochondrial degradation, neurodegenerative diseases, and ischemia or drug-induced tissue injury. removal of damaged mitochond ...022944659
fighting mycobacteria through isgylation. 201222940737
west nile virus growth is independent of autophagy activation.west nile virus (wnv) is an arthropod-borne virus with a worldwide distribution that causes neurologic disease and death. autophagy is a cellular homeostatic mechanism involved in antiviral responses but can be subverted to support viral growth as well. we show that autophagy is induced by wnv infection in cell culture and in primary neuron cultures. following wnv infection, lysosomes co-localize with autophagosomes resulting in lc3b-ii turnover and autolysosomal acidification. however, activati ...201222939285
antiviral chlorinated daphnane diterpenoid orthoesters from the bark and wood of trigonostemon cherrieri.the chemical study of the bark and the wood of trigonostemon cherrieri, a rare endemic plant of new caledonia, led to the isolation of a series of highly oxygenated daphnane diterpenoid orthoesters (ddo) bearing an uncommon chlorinated moiety: trigocherrins a-f and trigocherriolides a-d. herein, we describe the isolation and structure elucidation of the ddo (trigocherrins b-f and trigocherriolides a-d). we also report the antiviral activity of trigocherrins a, b and f (1, 2 and 6) and trigocherr ...201222938995
hepatitis c virus translation preferentially depends on active rna replication.hepatitis c virus (hcv) rna initiates its replication on a detergent-resistant membrane structure derived from the endoplasmic reticulum (er) in the hcv replicon cells. by performing a pulse-chase study of bru-labeled hcv rna, we found that the newly-synthesized hcv rna traveled along the anterograde-membrane traffic and moved away from the er. presumably, the rna moved to the site of translation or virion assembly in the later steps of viral life cycle. in this study, we further addressed how h ...201222937067
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 ...201222935804
convergent evolution of argonaute-2 slicer antagonism in two distinct insect rna viruses.rna interference (rnai) is a major antiviral pathway that shapes evolution of rna viruses. we show here that nora virus, a natural drosophila pathogen, is both a target and suppressor of rnai. we detected viral small rnas with a signature of dicer-2 dependent small interfering rnas in nora virus infected drosophila. furthermore, we demonstrate that the nora virus vp1 protein contains rnai suppressive activity in vitro and in vivo that enhances pathogenicity of recombinant sindbis virus in an rna ...201222916019
dephosphorylation of hur protein during alphavirus infection is associated with hur relocalization to the cytoplasm.we have demonstrated previously that the cellular hur protein binds u-rich elements in the 3' untranslated region (utr) of sindbis virus rna and relocalizes from the nucleus to the cytoplasm upon sindbis virus infection in 293t cells. in this study, we show that two alphaviruses, ross river virus and chikungunya virus, lack the conserved high-affinity u-rich hur binding element in their 3' utrs but still maintain the ability to interact with hur with nanomolar affinities through alternative bind ...201222915590
arf6-gef brag1 regulates jnk-mediated synaptic removal of glua1-containing ampa receptors: a new mechanism for nonsyndromic x-linked mental disorder.activity-dependent modifications of excitatory synapses contribute to synaptic maturation and plasticity, and are critical for learning and memory. consequently, impairments in synapse formation or synaptic transmission are thought to be responsible for several types of mental disabilities. brag1 is a guanine nucleotide exchange factor for the small gtp-binding protein arf6 that localizes to the postsynaptic density of excitatory synapses. mutations in brag1 have been identified in families with ...022915114
comprehensive proteomic analysis of nonintegrin laminin receptor interacting proteins.human nonintegrin laminin receptor is a multifunctional protein acting as an integral component of the ribosome and a cell surface receptor for laminin-1. the laminin receptor is overexpressed in several human cancers and is also the cell surface receptor for several viruses and pathogenic prion proteins, making it a pathologically significant protein. this study focused on the proteomic characterization of laminin receptor interacting proteins from mus musculus. the use of affinity chromatograp ...201222909348
dengue reporter viruses reveal viral dynamics in interferon receptor-deficient mice and sensitivity to interferon effectors in vitro.dengue virus (denv) is a global disease threat for which there are no approved antivirals or vaccines. establishing state-of-the-art screening systems that rely on fluorescent or luminescent reporters may accelerate the development of anti-denv therapeutics. however, relatively few reporter denv platforms exist. here, we show that denv can be genetically engineered to express a green fluorescent protein or firefly luciferase. reporter viruses are infectious in vitro and in vivo and are sensitive ...201222908290
eilat virus, a unique alphavirus with host range restricted to insects by rna replication.most alphaviruses and many other arboviruses are mosquito-borne and exhibit a broad host range, infecting many different vertebrates including birds, rodents, equids, humans, and nonhuman primates. consequently, they can be propagated in most vertebrate and insect cell cultures. this ability of arboviruses to infect arthropods and vertebrates is usually essential for their maintenance in nature. however, several flaviviruses have recently been described that infect mosquitoes but not vertebrates ...201222908261
degradation of host micrornas by poxvirus poly(a) polymerase reveals terminal rna methylation as a protective antiviral mechanism.the life cycle of several viruses involves host or virally encoded small noncoding rnas, which play important roles in posttranscriptional regulation. small noncoding rnas include micrornas (mirnas), which modulate the transcriptome, and small interfering rnas (sirnas), which are involved in pathogen defense in plants, worms, and insects. we show that insect and mammalian poxviruses induce the degradation of host mirnas. the virally encoded poly(a) polymerase, which polyadenylates viral transcri ...022901540
wing shape as an indicator of larval rearing conditions for aedes albopictus and aedes aegypti (diptera: culicidae).estimating a mosquito's vector competence, or likelihood of transmitting disease, if it takes an infectious bloodmeal, is an important aspect of predicting when and where outbreaks of infectious diseases will occur. vector competence can be affected by rearing temperature and inter- and intraspecific competition experienced by the individual mosquito during its larval development. this research investigates whether a new morphological indicator of larval rearing conditions, wing shape, can be us ...022897054
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 ...201222894924
testing of novel dengue virus 2 vaccines in african green monkeys: safety, immunogenicity, and efficacy.the immunogenicity and safety of three novel host-range vaccines containing deletions in the transmembrane domain of dengue virus serotype 2 (dv2) e glycoprotein were evaluated in african green monkeys. the shorter transmembrane domains are capable of functionally spanning an insect but not a mammalian cell membrane, resulting in production of viral mutants that have reduced infectivity in mammalian hosts but efficient growth in insect cells. groups of four monkeys received one dose each of test ...201222890035
pamps and damps: signal 0s that spur autophagy and immunity.pathogen-associated molecular pattern molecules (pamps) are derived from microorganisms and recognized by pattern recognition receptor (prr)-bearing cells of the innate immune system as well as many epithelial cells. in contrast, damage-associated molecular pattern molecules (damps) are cell-derived and initiate and perpetuate immunity in response to trauma, ischemia, and tissue damage, either in the absence or presence of pathogenic infection. most pamps and damps serve as so-called 'signal 0s' ...022889221
rnase l triggers autophagy in response to viral infections.autophagy is a programmed homeostatic response to diverse types of cellular stress that disposes of long-lived proteins, organelles, and invading microbes within double-membraned structures called autophagosomes. the 2',5'-oligoadenylate/rnase l system is a virus-activated host rnase pathway that disposes of or processes viral and cellular single-stranded rnas. here we report that activation of rnase l during viral infections induces autophagy. accordingly, infections with encephalomyocarditis v ...201222875977
translational regulation of anopheles gambiae mrnas in the midgut during plasmodium falciparum infection.malaria is caused by plasmodium parasites, which are transmitted via the bites of infected anopheline mosquitoes. midgut invasion is a major bottleneck for plasmodium development inside the mosquito vectors. malaria parasites in the midgut are surrounded by a hostile environment rich in digestive enzymes, while a rapidly responding immune system recognizes plasmodium ookinetes and recruits killing factors from the midgut and surrounding tissues, dramatically reducing the population of invading o ...201222857387
in vivo administration of recombinant alphavirus into rodents.the alphaviruses semliki forest virus (sfv) and sindbis virus (sin) have been used frequently as expression vectors in vitro and in vivo. usually, these systems consist of replication-deficient vectors that require a helper vector for packaging of recombinant particles. replication-proficient vectors have also been engineered. alphaviral vectors can be used as nucleic-acid-based vectors (dna and rna) or infectious particles. high-titer viral production is achieved in <2 d. the broad host range o ...201222854568
delivery of recombinant alphavirus into hippocampal slice tissue culture.the alphaviruses semliki forest virus (sfv) and sindbis virus (sin) have been used frequently as expression vectors in vitro and in vivo. usually, these systems consist of replication-deficient vectors that require a helper vector for packaging of recombinant particles. replication-proficient vectors have also been engineered. alphaviral vectors can be used as nucleic-acid-based vectors (dna and rna) or infectious particles. high-titer viral production is achieved in <2 d. the broad host range o ...201222854567
photodynamic inactivation of mammalian viruses and bacteriophages.photodynamic inactivation (pdi) has been used to inactivate microorganisms through the use of photosensitizers. the inactivation of mammalian viruses and bacteriophages by photosensitization has been applied with success since the first decades of the last century. due to the fact that mammalian viruses are known to pose a threat to public health and that bacteriophages are frequently used as models of mammalian viruses, it is important to know and understand the mechanisms and photodynamic proc ...201222852040
heterozygous tbk1 mutations impair tlr3 immunity and underlie herpes simplex encephalitis of childhood.childhood herpes simplex virus-1 (hsv-1) encephalitis (hse) may result from single-gene inborn errors of tlr3 immunity. tlr3-dependent induction of ifn-α/β or ifn-λ is crucial for protective immunity against primary hsv-1 infection in the central nervous system (cns). we describe here two unrelated children with hse carrying different heterozygous mutations (d50a and g159a) in tbk1, the gene encoding tank-binding kinase 1, a kinase at the crossroads of multiple ifn-inducing signaling pathways. b ...201222851595
neurogranin targets calmodulin and lowers the threshold for the induction of long-term potentiation.calcium entry and the subsequent activation of camkii trigger synaptic plasticity in many brain regions. the induction of long-term potentiation (ltp) in the ca1 region of the hippocampus requires a relatively high amount of calcium-calmodulin. this requirement is usually explained, based on in vitro and theoretical studies, by the low affinity of camkii for calmodulin. an untested hypothesis, however, is that calmodulin is not randomly distributed within the spine and its targeting within the s ...201222848456
genomic characterization of a novel virus of the family tymoviridae isolated from mosquitoes.the family tymoviridae comprises three plant virus genera, including tymovirus, marafivirus, and maculavirus, which are found in most parts of the world and cause severe agricultural losses. we describe a putatively novel member of the family tymoviridae, which is isolated from mosquitoes (culex spp.), referred to as cutlv.201222848363
engineered hepatitis b virus surface antigen l protein particles for in vivo active targeting of splenic dendritic cells.dendritic cells (dcs) are key regulators of adaptive t-cell responses. by capturing exogenous antigens and presenting antigen-derived peptides via major histocompatibility complex molecules to naïve t cells, dcs induce antigen-specific immune responses in vivo. in order to induce effective host immune responses, active delivery of exogenous antigens to dcs is considered important for future vaccine development. we recently generated bionanocapsules (bncs) consisting of hepatitis b virus surface ...201222848163
tumor-specific targeting with modified sindbis viral vectors: evaluation with optical imaging and positron emission tomography in vivo.sindbis virus (sinv) infect tumor cells specifically and systemically throughout the body. sindbis vectors are capable of expressing high levels of transduced suicide genes and thus efficiently produce enzymes for prodrug conversion in infected tumor cells. the ability to monitor suicide gene expression levels and viral load in patients, after administration of the vectors, would significantly enhance this tumor-specific therapeutic option.022847302
matching biochemical and functional efficacies confirm zip as a potent competitive inhibitor of pkmζ in neurons.pkmζ is an autonomously active, atypical protein kinase c (apkc) isoform that is both necessary and sufficient for maintaining long-term potentiation (ltp) and long-term memory. the myristoylated ζ-pseudosubstrate peptide, zip, potently inhibits pkmζ biochemically in vitro, within cultured cells, and within neurons in hippocampal slices, and reverses ltp maintenance and erases long-term memory storage. a recent study (wu-zhang et al., 2012), however, suggested zip was not effective on a pkmζ fus ...201222846225
a graph theory method for determination of cryo-em image focuses.accurate determination of micrograph focuses is essential for averaging multiple images to reach high-resolution 3-d reconstructions in electron cryo-microscopy (cryo-em). current methods use iterative fitting of focus-dependent simulated power spectra to the power spectra of experimental images, with the fitting performed independently for different images. here we have developed a novel graph theory based method in which the rotational average focus and individual angular sector focuses of all ...201222842112
a novel coding-region rna element modulates infectious dengue virus particle production in both mammalian and mosquito cells and regulates viral replication in aedes aegypti mosquitoes.dengue virus (denv) is an enveloped flavivirus with a positive-sense rna genome transmitted by aedes mosquitoes, causing the most important arthropod-borne viral disease affecting humans. relatively few cis-acting rna regulatory elements have been described in the denv coding-region. here, by introducing silent mutations into a denv-2 infectious clone, we identify the conserved capsid-coding region 1 (ccr1), an rna sequence element that regulates viral replication in mammalian cells and to a gre ...201222840606
an assembly model of rift valley fever virus.rift valley fever virus (rvfv) is a bunyavirus endemic to africa and the arabian peninsula that infects humans and livestock. the virus encodes two glycoproteins, gn and gc, which represent the major structural antigens and are responsible for host cell receptor binding and fusion. both glycoproteins are organized on the virus surface as cylindrical hollow spikes that cluster into distinct capsomers with the overall assembly exhibiting an icosahedral symmetry. currently, no experimental three-di ...201222837754
chikungunya virus nsp3 blocks stress granule assembly by recruitment of g3bp into cytoplasmic foci.chikungunya virus nonstructural protein nsp3 has an essential but unknown role in alphavirus replication and interacts with ras-gap sh3 domain-binding protein (g3bp). here we describe the first known function of nsp3, to inhibit stress granule assembly by recruiting g3bp into cytoplasmic foci. a conserved sh3 domain-binding motif in nsp3 is essential for both nsp3-g3bp interactions and viral rna replication. this study reveals a novel role for nsp3 as a regulator of the cellular stress response.201222837213
interaction of endogenous tau protein with synaptic proteins is regulated by n-methyl-d-aspartate receptor-dependent tau phosphorylation.amyloid-β and tau protein are the two most prominent factors in the pathology of alzheimer disease. recent studies indicate that phosphorylated tau might affect synaptic function. we now show that endogenous tau is found at postsynaptic sites where it interacts with the psd95-nmda receptor complex. nmda receptor activation leads to a selective phosphorylation of specific sites in tau, regulating the interaction of tau with fyn and the psd95-nmda receptor complex. based on our results, we propose ...201222833681
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 ...201222827926
targeted gene transfer of different genes to presynaptic and postsynaptic neocortical neurons connected by a glutamatergic synapse.genetic approaches to analyzing neuronal circuits and learning would benefit from a technology to first deliver a specific gene into presynaptic neurons, and then deliver a different gene into an identified subset of their postsynaptic neurons, connected by a specific synapse type. here, we describe targeted gene transfer across a neocortical glutamatergic synapse, using as the model the projection from rat postrhinal to perirhinal cortex. the first gene transfer, into the presynaptic neurons in ...201222820303
larval habitat characteristics of the genus anopheles (diptera: culicidae) and a checklist of mosquitoes in guilan province, northern iran.ecological data are important in the vector control management of mosquitoes. there is scattered published information about the larval habitat characteristics and ecology of the genus anopheles (diptera: culicidae) in iran and most of available data is in relation to malaria vectors in southern iran.201122808409
identifying host factors that regulate viral infection. 201222807672
loss of stress response as a consequence of viral infection: implications for disease and therapy.herein, we propose that viral infection can induce a deficient cell stress response and thereby impairs stress tolerance and makes tissues vulnerable to damage. having a valid paradigm to address the pathological impacts of viral infections could lead to effective new therapies for diseases that have previously been unresponsive to intervention. host response to viral infections can also lead to autoimmune diseases like type 1 diabetes. in the case of newcastle disease virus, the effects of vira ...201222797944
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 ...201222796170
antiviral activity of a small molecule deubiquitinase inhibitor occurs via induction of the unfolded protein response.ubiquitin (ub) is a vital regulatory component in various cellular processes, including cellular responses to viral infection. as obligate intracellular pathogens, viruses have the capacity to manipulate the ubiquitin (ub) cycle to their advantage by encoding ub-modifying proteins including deubiquitinases (dubs). however, how cellular dubs modulate specific viral infections, such as norovirus, is poorly understood. to examine the role of dubs during norovirus infection, we used wp1130, a small ...201222792064
autophagy and immunity - insights from human herpesviruses.the herpesviruses are a family of double-stranded dna viruses that infect a wide variety of organisms. having co-evolved with their hosts over millennia, herpesviruses have developed a large repertoire of mechanisms to manipulate normal cellular processes for their own benefit. consequently, studies on these viruses have made important contributions to our understanding of fundamental biological processes. here we describe recent research on the human herpesviruses that has contributed to our un ...201222783253
insights into the roles of local translation from the axonal transcriptome.much of our knowledge on the roles of intra-axonal translation derives from the characterization of a small number of individual mrnas that were found to be localized in axons. however, two recent studies, using large-scale approaches to provide a more comprehensive characterization of the axonal transcriptome, have led to the discovery of thousands of axonal mrnas. the apparent abundance of mrnas in axons raises the possibility that local translation has many more functions than previously thou ...022773949
humoral innate immune response and disease.the humoral innate immune response consists of multiple components, including the naturally occurring antibodies (nab), pentraxins and the complement and contact cascades. as soluble, plasma components, these innate proteins provide key elements in the prevention and control of disease. however, pathogens and cells with altered self proteins utilize multiple humoral components to evade destruction and promote pathology. many studies have examined the relationship between humoral immunity and aut ...201222771788
extended jak activation and delayed stat1 dephosphorylation contribute to the distinct signaling profile of cns neurons exposed to interferon-gamma.although interferon-gamma (ifn-γ) plays a critical role in the noncytolytic elimination of many neurotropic viral infections, the signaling response to this cytokine has not been extensively characterized in primary cns neurons. we previously demonstrated that the ifn-γ response at the signaling and gene expression levels is temporally extended in primary mouse hippocampal neurons, as compared to the transient response of primary mouse embryonic fibroblasts (mef). we hypothesize that the protrac ...201222769061
comprehensive biothreat cluster identification by pcr/electrospray-ionization mass 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 ...201222768032
how do viruses interact with stress-associated rna granules? 201222761570
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 ...201222761388
Displaying items 1101 - 1200 of 5405