PMID(sorted ascending)
interferon-like virus-inhibitor induced in human leukocytes by phytohemagglutinin.phytohemagglutinin, an extract of the kidney bean, phaseolus vulgaris, induces in human leukocyte cultures an inhibitor of the cytopathic effects of sindbis virus. the physicochemical and biological properties of this virus-inhibitor are similar to those of interferon induced by newcastle disease virus, except for an instability at ph 2 and 10 and at 56 degrees c.196517533668
posttranslational n-glycosylation of the hepatitis b virus large envelope protein.the addition of n-linked glycans to proteins is normally a cotranslational process that occurs during translocation of the nascent protein to the endoplasmic reticulum. here, we report on an exception to this rule occurring on the hepatitis b virus (hbv) large l envelope protein that is a subject to co-plus posttranslational n-glycosylation.200717537250
de novo initiation of rna synthesis by the arterivirus rna-dependent rna polymerase.all plus-strand rna viruses encode an rna-dependent rna polymerase (rdrp) that functions as the catalytic subunit of the viral replication/transcription complex, directing viral rna synthesis in concert with other viral proteins and, sometimes, host proteins. rna synthesis essentially can be initiated by two different mechanisms, de novo initiation and primer-dependent initiation. most viral rdrps have been identified solely on the basis of comparative sequence analysis, and for many viruses the ...200717537850
next generation: tuberculosis vaccines that elicit protective cd8+ t cells.tuberculosis continues to cause considerable human morbidity and mortality worldwide, particularly in people coinfected with hiv. the emergence of multidrug resistance makes the medical treatment of tuberculosis even more difficult. thus, the development of a tuberculosis vaccine is a global health priority. here we review the data concerning the role of cd8+ t cells in immunity to tuberculosis and consider how cd8+ t cells can be elicited by vaccination. many immunization strategies have the po ...200717542758
novel toxicity of the unedited glur2 ampa receptor subunit dependent on surface trafficking and increased ca2+-permeability.rna editing modifies the glur2 ampa receptor subunit pore loop at the q/r site and limits receptor ca(2+) permeability. editing failure is implicated in neurodegenerative diseases, including amyotrophic lateral sclerosis. we show that channels with unedited glur2 are highly toxic in cultured hippocampal neurons. toxicity exceeds that of other ca(2+)-permeable ampa receptor types and is influenced by agonist binding site mutations, ability to desensitize, and extracellular ca(2+) levels. signific ...200717544687
the inhibitors of protein acylation, cerulenin and tunicamycin, increase voltage-dependent ca(2+) currents in the insulin-secreting ins 832/13 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 ...200717548064
neuroprotective interventions targeting detrimental host immune responses protect mice from fatal alphavirus encephalitis.systemic treatment with the tetracycline derivative, minocycline, attenuates neurologic deficits in animal models of amyotrophic lateral sclerosis, hypoxic-ischemic brain injury, and multiple sclerosis. inhibition of microglial activation within the cns is 1 mechanism proposed to underlie the beneficial effects of the drug in these systems. given the widening scope of acute viral encephalitis caused by mosquito-borne pathogens, we investigated the therapeutic effects of minocycline in a murine m ...200717549013
environment determines fidelity for an rna virus replicase.the rate of insertion and deletion mutations of the replicase of cucumber mosaic virus (cmv) was determined in planta by using a parasitic satellite rna (satrna) as a reporter. we found that the cmv replicase had different fidelity in different environments, with important implications in viral disease evolution. insertions were very rare events, irrespective of the region of the satrna genome assayed and independent of the hosts tested. on the other hand, deletion events were more frequent but ...200717553888
semliki forest virus nonstructural protein 2 is involved in suppression of the type i interferon response.the type i interferons (ifns) are potent mediators of antiviral immunity, and many viruses have developed means to block their expression or their effects. semliki forest virus (sfv) infection induces rapid and profound silencing of host cell gene expression, a process believed to be important for the inhibition of the ifn response. in sfv-infected cells, a large proportion of the nonstructural protein nsp2 is found in the nucleus, but a role for this localization has not been described. in this ...200717553895
mutations at the palmitoylation site of non-structural protein nsp1 of semliki forest virus attenuate virus replication and cause accumulation of compensatory mutations.the replicase of semliki forest virus (sfv) consists of four non-structural proteins, designated nsp1-4, and is bound to cellular membranes via an amphipathic peptide and palmitoylated cysteine residues of nsp1. it was found that mutations preventing nsp1 palmitoylation also attenuated virus replication. the replacement of these cysteines by alanines, or their deletion, abolished virus viability, possibly due to disruption of interactions between nsp1 and nsp4, which is the catalytic subunit of ...200717554031
use of sentinel chickens to study the transmission dynamics of west nile virus in a sahelian ecosystem.during the 2003 rainy season, a follow-up survey in sentinel chickens was undertaken to assess the seasonal transmission of west nile virus (wnv) in a sahelian ecosystem: the ferlo (senegal). the estimated incidence rate in chickens was 14% (95% ci 7-29), with a very low level of transmission between july and september, and a transmission peak occurring between september and october. comparing these results with the estimate obtained from a previous transversal serological study performed on hor ...200817559695
heterogeneous nuclear ribonuclear protein k interacts with sindbis virus nonstructural proteins and viral subgenomic mrna.alphaviruses are a group of arthropod-borne human and animal pathogens that can cause epidemics of significant public health and economic consequence. alphavirus rna synthesis requires four virally encoded nonstructural proteins and probably a number of cellular proteins. using comparative two-dimensional electrophoresis we were able to identify proteins enriched in cytoplasmic membrane fractions containing viral rna synthetic complexes following infection with sindbis virus. our studies demonst ...200717561226
human muscle satellite cells as targets of chikungunya virus infection.chikungunya (chik) virus is a mosquito-transmitted alphavirus that causes in humans an acute infection characterised by fever, polyarthralgia, head-ache, and myalgia. since 2005, the emergence of chik virus was associated with an unprecedented magnitude outbreak of chik disease in the indian ocean. clinically, this outbreak was characterized by invalidating poly-arthralgia, with myalgia being reported in 97.7% of cases. since the cellular targets of chik virus in humans are unknown, we studied t ...200717565380
the early protective thymus-independent antibody response to foot-and-mouth disease virus is mediated by splenic cd9+ b lymphocytes.infection of mice with cytopathic foot-and-mouth disease virus (fmdv) induces a rapid and specific thymus-independent (ti) neutralizing antibody response that promptly clears the virus. herein, it is shown that fmdv-infected dendritic cells (dcs) directly stimulate splenic innate-like cd9(+) b lymphocytes to rapidly (3 days) produce neutralizing anti-fmdv immunoglobulin m antibodies without t-lymphocyte collaboration. in contrast, neither follicular (cd9(-)) b lymphocytes from the spleen nor b l ...200717567692
coincident regulation of pkcdelta in human platelets by phosphorylation of tyr311 and tyr565 and phospholipase c signalling.pkc (protein kinase c)d plays a complex role in platelets, having effects on both positive and negative signalling functions. it is phosphorylated on tyrosine residues in response to thrombin and collagen, and it has recently been shown that tyr311 is phosphorylated in response to par (protease-activated receptor) 1 and par4 receptor activation. in the present study, we show that tyr311 and tyr565 are phosphorylated in response to thrombin, and have examined the interplay between phosphorylation ...200717570831
viruses as anticancer drugs.oncolytic viruses are being developed as anticancer drugs. they propagate selectively in tumor tissue and destroy it without causing excessive damage to normal non-cancerous tissues. when used as drugs, they must meet stringent criteria for safety and efficacy and be amenable to pharmacological study in human subjects. specificity for neoplastic tissue is the key to safety, and this goal can be achieved through a variety of ingenious virus-engineering strategies. antiviral immunity remains a sig ...200717573126
effect of ceramide n-acyl chain and polar headgroup structure on the properties of ordered lipid domains (lipid rafts).ceramides are sphingolipids that greatly stabilize ordered membrane domains (lipid rafts), and displace cholesterol from them. ceramide-rich rafts have been implicated in diverse biological processes. because ceramide analogues have been useful for probing the biological function of ceramide, and may have biomedical applications, it is important to characterize how ceramide structure affects membrane properties, including lipid raft stability and composition. in this report, fluorescence quenchi ...200717574203
regulation of dendritic excitability by activity-dependent trafficking of the a-type k+ channel subunit kv4.2 in hippocampal neurons.voltage-gated a-type k+ channel kv4.2 subunits are highly expressed in the dendrites of hippocampal ca1 neurons. however, little is known about the subcellular distribution and trafficking of kv4.2-containing channels. here we provide evidence for activity-dependent trafficking of kv4.2 in hippocampal spines and dendrites. live imaging and electrophysiological recordings showed that kv4.2 internalization is induced rapidly upon glutamate receptor stimulation. kv4.2 internalization was clathrin m ...200717582333
synthesis of some novel thiourea derivatives obtained from 5-[(4-aminophenoxy)methyl]-4-alkyl/aryl-2,4-dihydro-3h-1,2,4-triazole-3-thiones and evaluation as antiviral/anti-hiv and anti-tuberculosis a continuation of our previous efforts on n-alkyl/aryl-n'-[4-(4-alkyl/aryl-2,4-dihydro-3h-1,2,4-triazole-3-thione-5-yl)phenyl]thioureas 1-19 and n-alkyl/aryl-n'-[4-(3-aralkylthio-4-alkyl/aryl-4h-1,2,4-triazole-5-yl)phenyl]thioureas 20-22, a series of novel 5-[(4-aminophenoxy)methyl]-4-alkyl/aryl-2,4-dihydro-3h-1,2,4-triazole-3-thiones 23-26 and several related thioureas, n-alkyl/aryl-n'-{4-[(4-alkyl/aryl-5-thioxo-4,5-dihydro-1h-1,2,4-triazol-3-yl)methoxy]phenyl}thioureas 27-42 were synthesize ...200817583388
pd-catalyzed c-c bond-forming reactions of thymidine mesitylene sulfonate.facile synthesis of c-4 aryl pyrimidinone nucleoside analogues from an easily prepared o4-arylsulfonate derivative of thymidine is reported. two o4-arylsulfonylthymidine precursors, (4-methylphenyl)sulfonyl and (2,4,6-trimethylphenyl)sulfonyl, were prepared and analyzed for their stabilities. of the two, the latter possessed suitable stability as well as reactivity for pd-catalyzed c-c bond-forming reactions with a variety of arylboronic acids. these reactions at the c-4 position are nontrivial ...200717595142
comparison of four methods using throat swabs to confirm rubella virus infection.laboratory tests are essential for confirming sporadic cases and outbreaks of rubella. detection of rubella virus is often necessary to confirm rubella cases and to identify specimens to be used to characterize wild-type rubella viruses. the sensitivities of four methods for detecting rubella virus infection using throat swabs, which had been collected in henan and anhui provinces in china, were evaluated. the methods used were reverse transcription (rt)-pcr followed by southern hybridization us ...200717596370
characterization of reemerging chikungunya unprecedented epidemic of chikungunya virus (chikv) infection recently started in countries of the indian ocean area, causing an acute and painful syndrome with strong fever, asthenia, skin rash, polyarthritis, and lethal cases of encephalitis. the basis for chikungunya disease and the tropism of chikv remain unknown. here, we describe the replication characteristics of recent clinical chikv strains. human epithelial and endothelial cells, primary fibroblasts and, to a lesser extent, monocyte ...200717604450
role of the cytoplasmic tail domains of bunyamwera orthobunyavirus glycoproteins gn and gc in virus assembly and morphogenesis.the m rna genome segment of bunyamwera virus (bunv), the prototype of the bunyaviridae family, encodes a precursor polyprotein that is proteolytically cleaved to yield two structural proteins, gn and gc, and a nonstructural protein called nsm. gn and gc are type i integral transmembrane glycoproteins. the gn protein contains a predicted cytoplasmic tail (ct) of 78 residues, and gc has a shorter ct of 25 residues. little is known about the role of the gn and gc ct domains in the virus replication ...200717609275
alpha-beta t cells provide protection against lethal encephalitis in the murine model of veev infection.we evaluated the safety and immunogenicity of a chimeric alphavirus vaccine candidate in mice with selective immunodeficiencies. this vaccine candidate was highly attenuated in mice with deficiencies in the b and t cell compartments, as well as in mice with deficient gamma-interferon responsiveness. however, the level of protection varied among the strains tested. wild type mice were protected against lethal veev challenge. in contrast, alpha/beta (alphabeta) tcr-deficient mice developed lethal ...200717610927
a dna prime, orally delivered protein boost vaccination strategy against viral encephalitis.arboviruses of the families togaviridae and flaviviridae are widely distributed and are important causative agents of viral encephalitis, a severe and often fatal disease. the only internationally available vaccine against these diseases is expensive and laborious to manufacture and difficult to administer. therefore, new vaccines are required against these pathogens. this study investigates the use of a dna-prime, orally delivered protein boost vaccination strategy against viral encephalitis. t ...200717613719
efficient replication, and evolution of sindbis virus genomes with non-canonical 3'a/u-rich elements (nc3are) in neonatal mice.sindbis virus (sin) is a mosquito-transmitted animal rna virus. we previously reported that sin genomes lacking a canonical 19 nt 3'cse undergo novel repair processes in bhk cells to generate a library of stable atypical sin genomes with non-canonical 3'a/u-rich elements (nc3ares) adjacent to the 3' poly(a) tail [1]. to determine the stability and evolutionary pressures on the sin genomes with nc3ares to regain a 3'cse, five representative sin isolates and a wild type sin were tested in newborn ...200717616797
anopheles gambiae heat shock protein cognate 70b impedes o'nyong-nyong virus replication.phylogenetic and functional analysis was conducted on an anopheles gambiae gene, ensangg00000017398. based on phylogenetic analysis, this gene belongs to the same lineage as heat shock protein cognate 70-4 (hsc70-4) in drosophila. accordingly, we propose to name this gene heat shock protein cognate 70b (hsc70b). we previously reported that expression of hsc70b and other genes including elongation factor-1alpha (ef-1alpha) and the agglutinin attachment subunit (agglutinin) were up-regulated in o' ...200717625007
characterization and expression patterns of let-7 microrna in the silkworm (bombyx mori).lin-4 and let-7, the two founding members of heterochronic microrna genes, are firstly confirmed in caenorhabditis elegans to control the proper timing of developmental programs in a heterochronic pathway. let-7 has been thought to trigger the onset of adulthood across animal phyla. ecdysone and broad-complex are required for the temporal expression of let-7 in drosophila melanogaster. for a better understanding of the conservation and functions of let-7, we seek to explore how it is expressed i ...200717651473
an immunogenic and protective alphavirus replicon particle-based dengue vaccine overcomes maternal antibody interference in weanling mice.a candidate pediatric dengue virus (denv) vaccine based on nonpropagating venezuelan equine encephalitis virus replicon particles (vrp) was tested for immunogenicity and protective efficacy in weanling mice in the presence and absence of potentially interfering maternal antibodies. a gene cassette encoding envelope proteins prm and e from mouse-adapted denv type 2 (denv2) strain ngc was cloned into a vee replicon vector and packaged into vrp, which programmed proper in vitro expression and proce ...200717652394
nuclear import and export of venezuelan equine encephalitis virus nonstructural protein 2.many rna viruses, which replicate predominantly in the cytoplasm, have nuclear components that contribute to their life cycle or pathogenesis. we investigated the intracellular localization of the multifunctional nonstructural protein 2 (nsp2) in mammalian cells infected with venezuelan equine encephalitis virus (vee), an important, naturally emerging zoonotic alphavirus. vee nsp2 localizes to both the cytoplasm and the nucleus of mammalian cells in the context of infection and also when express ...200717652399
a novel dual-targeted lentiviral vector leads to specific transduction of prostate cancer bone metastases in vivo after systemic administration.targeted gene transduction to organs and tissues of interest is the ultimate goal of therapeutic gene delivery. lentiviral vectors (lvs) are powerful tools for stable gene delivery but their integration into undesired cell types poses a serious safety concern for their use in the clinic. here we report the development of a new dual-targeted lv that can preferentially home to and express in prostate cancer bone metastases in vivo after systemic delivery. transductional targeting is mediated by a ...200717653099
screen for isg15-crossreactive deubiquitinases.the family of ubiquitin-like molecules (ubls) comprises several members, each of which has sequence, structural, or functional similarity to ubiquitin. isg15 is a homolog of ubiquitin in vertebrates and is strongly upregulated following induction by type i interferon. isg15 can be covalently attached to proteins, analogous to ubiquitination and with actual support of ubiquitin conjugating factors. specific proteases are able to reverse modification with ubiquitin or ubls by hydrolyzing the coval ...200717653289
the cytoplasmic tails of uukuniemi virus (bunyaviridae) g(n) and g(c) glycoproteins are important for intracellular targeting and the budding of virus-like particles.functional motifs within the cytoplasmic tails of the two glycoproteins g(n) and g(c) of uukuniemi virus (uuk) (bunyaviridae family) were identified with the help of our recently developed virus-like particle (vlp) system for uuk virus (a. k. overby, v. popov, e. p. neve, and r. f. pettersson, j. virol. 80:10428-10435, 2006). we previously reported that information necessary for the packaging of ribonucleoproteins into vlps is located within the g(n) cytoplasmic tail (a. k. overby, r. f. petters ...200717670814
west nile virus-induced neuroinflammation: glial infection and capsid protein-mediated neurovirulence.west nile virus (wnv) infection causes neurological disease at all levels of the neural axis, accompanied by neuroinflammation and neuronal loss, although the underlying mechanisms remain uncertain. given the substantial activation of neuroinflammatory pathways observed in wnv infection, we hypothesized that wnv-mediated neuroinflammation and cell death occurred through wnv infection of both glia and neurons, which was driven in part by wnv capsid protein expression. analysis of autopsied neural ...200717670819
enhanced priming of adaptive immunity by a proapoptotic mutant of mycobacterium tuberculosis.the inhibition of apoptosis of infected host cells is a well-known but poorly understood function of pathogenic mycobacteria. we show that inactivation of the seca2 gene in mycobacterium tuberculosis, which encodes a component of a virulence-associated protein secretion system, enhanced the apoptosis of infected macrophages by diminishing secretion of mycobacterial superoxide dismutase. deletion of seca2 markedly increased priming of antigen-specific cd8(+) t cells in vivo, and vaccination of mi ...200717671656
non-pathogenic sindbis virus causes hemorrhagic fever in the absence of alpha/beta and gamma interferons.the role of interferon-gamma (ifngamma) in antiviral innate immune responses during acute alphavirus infection is not well defined. we examined the contribution of ifngamma to the protection of adult mice from sindbis virus (sb)-induced disease by comparing subcutaneous infection of mice lacking receptors for either ifnalpha/beta (a129), ifngamma (g129) or both (ag129) to normal mice (wt129). while neither g129 nor wt129 mice exhibited clinical signs of disease, infection of a129 or ag129 mice w ...200717681583
identification and characterization of interferon-induced proteins that inhibit alphavirus replication.alpha/beta interferon (ifn-alpha/beta) produces antiviral effects through upregulation of many interferon-stimulated genes (isgs) whose protein products are effectors of the antiviral state. previous data from our laboratory have shown that ifn-alpha/beta can limit sindbis virus (sb) replication through protein kinase r (pkr)-dependent and pkr-independent mechanisms and that one pkr-independent mechanism inhibits translation of the infecting virus genome (k. d. ryman et al., j. virol. 79:1487-14 ...200717686841
the imidazopyrrolopyridine analogue ag110 is a novel, highly selective inhibitor of pestiviruses that targets the viral rna-dependent rna polymerase at a hot spot for inhibition of viral replication.ethyl 2-methylimidazo[1,2-a]pyrrolo[2,3-c]pyridin-8-carboxylate (ag110) was identified as a potent inhibitor of pestivirus replication. the 50% effective concentration values for inhibition of bovine viral diarrhea virus (bvdv)-induced cytopathic effect, viral rna synthesis, and production of infectious virus were 1.2 +/- 0.5 microm, 5 +/- 1 microm, and 2.3 +/- 0.3 microm, respectively. ag110 proved inactive against the hepatitis c virus and a flavivirus. ag110 inhibits bvdv replication at a tim ...200717686854
proteolytic processing of turnip yellow mosaic virus replication proteins and functional impact on infectivity.turnip yellow mosaic virus (tymv), a positive-strand rna virus belonging to the alphavirus-like supergroup, encodes its nonstructural replication proteins as a 206k precursor with domains indicative of methyltransferase (mt), proteinase (pro), ntpase/helicase (hel), and polymerase (pol) activities. subsequent processing of 206k generates a 66k protein encompassing the pol domain and uncharacterized 115k and 85k proteins. here, we demonstrate that tymv proteinase mediates an additional cleavage b ...200717686855
viral defense, carcinogenesis and isg15: novel roles for an old isg.recent studies have established that type i interferon modulates expression of large number of cellular genes. while the proteins encoded by some of these genes have a direct antiviral activity, the functions of the majority of the others have not yet been determined. one of the first identified ifn stimulated gene, encodes ubiquitin like protein isg15 that is also expressed in response to different stress stimuli. although it was shown that isg15 functions as protein modifier, it has been only ...200717689132
antiviral immunity directed by small rnas.plants and invertebrates can protect themselves from viral infection through rna silencing. this antiviral immunity involves production of virus-derived small interfering rnas (virnas) and results in specific silencing of viruses by virna-guided effector complexes. the proteins required for virna production as well as several key downstream components of the antiviral immunity pathway have been identified in plants, flies, and worms. meanwhile, viral mechanisms to suppress this small rna-directe ...200717693253
arenavirus entry occurs through a cholesterol-dependent, non-caveolar, clathrin-mediated endocytic mechanism.arenaviruses are important causes of viral hemorrhagic fevers in humans. arenavirus infection of cells occurs via a ph-dependent endocytic route, but detailed studies of entry pathways have not been done. we investigated the role of cell membrane cholesterol, caveolae, and clathrin coated pits in infection by lassa virus (lasv), which utilizes alpha-dystroglycan (alpha-dg) as a receptor, and pichindé virus (picv), which does not. depletion of cellular cholesterol by treatment with methyl betacyc ...200717698159
analysis of the selective advantage conferred by a c-e1 fusion protein synthesized by rubella virus di rnas.during serial passaging of rubella virus (rub) in cell culture, the dominant species of defective-interfering rna (di) generated contains an in-frame deletion between the capsid protein (c) gene and e1 glycoprotein gene resulting in production of a c-e1 fusion protein that is necessary for the maintenance of the di [tzeng, w.p., frey, t.k. (2006). c-e1 fusion protein synthesized by rubella virus di rnas maintained during serial passage. virology 356 198-207.]. a bhk cell line stably expressing t ...200717698161
averaging tens to hundreds of icosahedral particle images to resolve protein secondary structure elements using a multi-path simulated annealing optimization algorithm.accurately determining a cryoem particle's alignment parameters is crucial to high resolution single particle 3-d reconstruction. we developed multi-path simulated annealing, a monte-carlo type of optimization algorithm, for globally aligning the center and orientation of a particle simultaneously. a consistency criterion was developed to ensure the alignment parameters are correct and to remove some bad particles from a large pool of images of icosahedral particles. without using any a priori m ...200717698370
the delta2 'ionotropic' glutamate receptor functions as a non-ionotropic receptor to control cerebellar synaptic plasticity.the delta2 glutamate receptor (glurdelta2) belongs to the ionotropic glutamate receptor (iglur) family and plays a crucial role in the induction of cerebellar long-term depression (ltd), a form of synaptic plasticity underlying motor learning. nevertheless, the mechanisms by which glurdelta2 regulates cerebellar ltd have remained elusive. because a mutation occurring in lurcher mice causes continuous glurdelta2 channel activity that can be abolished by 1-naphtylacetylspermine (nasp), a channel b ...200717702810
venezuelan equine encephalitis virus infection of mosquito cells requires acidification as well as mosquito homologs of the endocytic proteins rab5 and rab7.venezuelan equine encephalitis virus (veev) is a new world alphavirus that can cause fatal encephalitis in humans. it remains a naturally emerging disease as well as a highly developed biological weapon. veev is transmitted to humans in nature by mosquito vectors. little is known about veev entry, especially in mosquito cells. here, a novel luciferase-based virus entry assay is used to show that the entry of veev into mosquito cells requires acidification. furthermore, mosquito homologs of key h ...200717707875
the atg5 atg12 conjugate associates with innate antiviral immune responses.autophagy is an essential process for physiological homeostasis, but its role in viral infection is only beginning to be elucidated. we show here that the atg5-atg12 conjugate, a key regulator of the autophagic process, plays an important role in innate antiviral immune responses. atg5-deficient mouse embryonic fibroblasts (mefs) were resistant to vesicular stomatitis virus replication, which was largely due to hyperproduction of type i interferons in response to immunostimulatory rna (isrna), s ...200717709747
production of pseudoinfectious yellow fever virus with a two-component genome.application of genetically modified, deficient-in-replication flaviviruses that are incapable of developing productive, spreading infection is a promising means of designing safe and effective vaccines. here we describe a two-component genome yellow fever virus (yfv) replication system in which each of the genomes encodes complete sets of nonstructural proteins that form the replication complex but expresses either only capsid or prm/e instead of the entire structural polyprotein. upon delivery ...200717715227
identification of novel small-molecule inhibitors of west nile virus infection.west nile virus (wnv) has spread throughout the united states and canada and now annually causes a clinical spectrum of human disease ranging from a self-limiting acute febrile illness to acute flaccid paralysis and lethal encephalitis. no therapy or vaccine is currently approved for use in humans. using high-throughput screening assays that included a luciferase expressing wnv subgenomic replicon and an ns1 capture enzyme-linked immunosorbent assay, we evaluated a chemical library of over 80,00 ...200717715228
characterization of the early events in dengue virus cell entry by biochemical assays and single-virus this study, we investigated the cell entry characteristics of dengue virus (denv) type 2 strain s1 on mosquito, bhk-15, and bs-c-1 cells. the concentration of virus particles measured by biochemical assays was found to be substantially higher than the number of infectious particles determined by infectivity assays, leading to an infectious unit-to-particle ratio of approximately 1:2,600 to 1:72,000, depending on the specific assays used. in order to explain this high ratio, we investigated th ...200717728239
aug_hairpin: prediction of a downstream secondary structure influencing the recognition of a translation start site.the translation start site plays an important role in the control of translation efficiency of eukaryotic mrnas. the recognition of the start aug codon by eukaryotic ribosomes is considered to depend on its nucleotide context. however, the fraction of eukaryotic mrnas with the start codon in a suboptimal context is relatively large. it may be expected that mrna should possess some features providing efficient translation, including the proper recognition of a translation start site. it has been ...200717760957
role of 3-o-sulfated heparan sulfate in virus-induced polykaryocyte way herpes simplex virus type-1 (hsv-1) spreads in vivo is by polykaryocytes formation. here we demonstrate that polykaryocyte production during hsv-1 spread in cultured human corneal fibroblasts (cf) required heparan sulfate (hs) and more specifically 3-o sulfated hs (3-os hs). the polykaryocyte formation heavily depended on the expression of hs on target (cf) cells but not on glycoprotein expressing effector cells. furthermore, we provide the first visual evidence of 3-os hs and hsv-1 gd c ...200717765228
ifn regulatory factor family members differentially regulate the expression of type iii ifn (ifn-lambda) genes.virus replication induces the expression of antiviral type i (ifn-alphabeta) and type iii (ifn-lambda1-3 or il-28a/b and il-29) ifn genes via tlr-dependent and -independent pathways. although type iii ifns differ genetically from type i ifns, their similar biological antiviral functions suggest that their expression is regulated in a similar fashion. structural and functional characterization of the ifn-lambda1 and ifn-lambda3 gene promoters revealed them to be similar to ifn-beta and ifn-alpha ...200717785777
role of autophagy in breast cancer.autophagy is an evolutionarily conserved process of cytoplasm and cellular organelle degradation in lysosomes. autophagy is a survival pathway required for cellular viability during starvation; however, if it proceeds to completion, autophagy can lead to cell death. in neurons, constitutive autophagy limits accumulation of polyubiquitinated proteins and prevents neuronal degeneration. therefore, autophagy has emerged as a homeostatic mechanism regulating the turnover of long-lived or damaged pro ...200717786023
viral encounters with 2',5'-oligoadenylate synthetase and rnase l during the interferon antiviral response. 200717804500
interferon-like virus-inhibitor induced in human leukocytes by phytohemagglutinin.phytohemagglutinin, an extract of the kidney bean, phaseolus vulgaris, induces in human leukocyte cultures an inhibitor of the cytopathic effects of sindbis virus. the physicochemical and biological properties of this virus-inhibitor are similar to those of interferon induced by newcastle disease virus, except for an instability at ph 2 and 10 and at 56 degrees c.196517838106
arthritis and arthralgia three years after sindbis virus infection: clinical follow-up of a cohort of 49 patients.sindbis virus (sinv) emerges as large human outbreaks in northern europe every 7 years. similar to many other alphaviruses, sinv is a mosquito-borne causative agent of a rash-arthritis. previous reports suggest that in many alphavirus infections joint symptoms might persist for years. a prospective cohort of 49 patients was physically examined 3 y after verified acute sinv infection to reveal persistent joint symptoms. we carefully searched for a temporal association between the infection and cu ...200817852949
analysis of the role of autophagy in replication of herpes simplex virus in cell culture.the herpes simplex virus type 1 (hsv-1) neurovirulence gene encoding icp34.5 controls the autophagy pathway. hsv-1 strains lacking icp34.5 are attenuated in growth and pathogenesis in animal models and in primary cultured cells. while this growth defect has been attributed to the inability of an icp34.5-null virus to counteract the induction of translational arrest through the pkr antiviral pathway, the role of autophagy in the regulation of hsv-1 replication is unknown. here we show that hsv-1 ...200717855538
rubella virus-induced superinfection exclusion studied in cells with persisting replicons.for the first time, homologous superinfection exclusion was documented for rubella virus (rub) by using vero cells harbouring persisting rub replicons. infection with wild-type rub was reduced by tenfold, whereas sindbis virus infection was unaffected. replication following infection with packaged replicons and transfection with replicon transcripts was also restricted in these cells, indicating that restriction occurred after penetration and entry. translation of such 'supertransfecting' replic ...200717872530
structural and functional analyses of stem-loop 1 of the sindbis virus genome.alphavirus genome function is controlled by elements at both the 5' and 3' ends. the 5' 220 nt of the sindbis virus genome is predicted to consist of four stem-loop structures the first of which has been demonstrated to be required for efficient minus-strand rna synthesis. to understand the role of the structure of the first stem-loop (sl1) in regulating genome function, we performed enzymatic and chemical probing analyses. there were significant differences between the computer-predicted struct ...200817900652
novel vectors expressing anti-apoptotic protein bcl-2 to study cell death in semliki forest virus-infected cells.semliki forest virus (sfv, alphavirus) induce rapid shut down of host cell protein synthesis and apoptotic death of infected vertebrate cells. data on alphavirus-induced apoptosis are controversial. in this study, the anti-apoptotic bcl-2 gene was placed under the control of duplicated subgenomic promoter or different internal ribosome entry sites (ires) and expressed using a novel bicistronic sfv vector. the use of ires containing vectors resulted in high-level bcl-2 synthesis during the early ...200817904678
chimeric sindbis/eastern equine encephalitis vaccine candidates are highly attenuated and immunogenic in mice.we developed chimeric sindbis (sinv)/eastern equine encephalitis (eeev) viruses and investigated their potential for use as live virus vaccines against eeev. one vaccine candidate contained structural protein genes from a typical north american eeev strain, while the other had structural proteins from a naturally attenuated brazilian isolate. both chimeric viruses replicated efficiently in mammalian and mosquito cell cultures and were highly attenuated in mice. vaccinated mice did not develop de ...200717904699
increased immunogenicity of a dna-launched venezuelan equine encephalitis virus-based replicon dna vaccine.a novel genetic vaccine that is based on a venezuelan equine encephalitis virus (vee) replicon launched from plasmid dna is described. the plasmid encodes a vee replicon under the transcriptional control of the cytomegalovirus immediate-early promoter (vee dna). the vee dna consistently expressed 3- to 15-fold more green fluorescent protein in vitro than did a conventional dna vaccine. furthermore, transfection with the dna-launched vee replicon induced apoptosis and type i interferon production ...200717913817
analysis of venezuelan equine encephalitis virus capsid protein function in the inhibition of cellular transcription.the encephalitogenic new world alphaviruses, including venezuelan (veev), eastern (eeev), and western equine encephalitis viruses, constitute a continuing public health threat in the united states. they circulate in central, south, and north america and have the ability to cause fatal disease in humans and in horses and other domestic animals. we recently demonstrated that these viruses have developed the ability to interfere with cellular transcription and use it as a means of downregulating a ...200717913819
type i interferons are essential in controlling neurotropic coronavirus infection irrespective of functional cd8 t cells.neurotropic coronavirus infection induces expression of both beta interferon (ifn-beta) rna and protein in the infected rodent central nervous system (cns). however, the relative contributions of type i ifn (ifn-i) to direct, cell-type-specific virus control or cd8 t-cell-mediated effectors in the cns are unclear. ifn-i receptor-deficient (ifnar(-/-)) mice infected with a sublethal and demyelinating neurotropic virus variant and those infected with a nonpathogenic neurotropic virus variant both ...200817928334
venezuelan equine encephalitis virus replicon particles encoding respiratory syncytial virus surface glycoproteins induce protective mucosal responses in mice and cotton rats.respiratory syncytial virus (rsv) is an important viral pathogen that causes severe lower respiratory tract infection in infants, the elderly, and immunocompromised individuals. there are no licensed rsv vaccines to date. to prevent rsv infection, immune responses in both the upper and lower respiratory tracts are required. previously, immunization with venezuelan equine encephalitis virus replicon particles (vrps) demonstrated effectiveness in inducing mucosal protection against various pathoge ...200717928349
the zinc finger antiviral protein acts synergistically with an interferon-induced factor for maximal activity against alphaviruses.type i interferons (ifns) signal through specific receptors to mediate expression of genes, which together confer a cellular antiviral state. overexpression of the zinc finger antiviral protein (zap) imparts a cellular antiviral state against retroviridae, togaviridae, and filoviridae virus family members. since zap expression is induced by ifn, we utilized sindbis virus (sinv) to investigate the role of other ifn-induced factors in zap's inhibitory potential. overexpressed zap did not inhibit v ...200717928353
long-term protection in hamsters against human parainfluenza virus type 3 following mucosal or combinations of mucosal and systemic immunizations with chimeric alphavirus-based replicon licensed vaccines are available to protect against parainfluenza virus type 3 (piv3), a significant health risk for infants. in search of a safe vaccine, we used an alphavirus-based chimeric vector, consisting of sindbis virus (sin) structural proteins and venezuelan equine encephalitis virus (vee) replicon rna, expressing the piv3 hemagglutinin-neuraminidase (hn) glycoprotein (vee/sin-hn). we compared different routes of intramuscular (i.m.), intranasal (i.n.), or combined i.n. and i.m. immu ...200717944814
beta7-integrin-independent enhancement of mucosal and systemic anti-hiv antibody responses following combined mucosal and systemic gene delivery.vaccination strategies that can block or limit heterosexual human immunodeficiency virus (hiv) transmissions to local and systemic tissues are the goal of much research effort. herein, in a mouse model, we aimed to determine whether the enhancement of antibody responses through mucosal and systemic immunizations, previously observed with protein-based vaccines, applies to immunizations with dna- or rna-based vectors. intranasal (i.n.) followed by intramuscular (i.m.) immunizations (i.n./i.m.) wi ...200817944930
cytopathic mechanisms of hiv-1.the human immunodeficiency virus type 1 (hiv-1) has been intensely investigated since its discovery in 1983 as the cause of acquired immune deficiency syndrome (aids). with relatively few proteins made by the virus, it is able to accomplish many tasks, with each protein serving multiple functions. the envelope glycoprotein, composed of the two noncovalently linked subunits, su (surface glycoprotein) and tm (transmembrane glycoprotein) is largely responsible for host cell recognition and entry re ...200717945027
a dual-targeted lentiviral vector homing in on prostate bone metastases. 200717948046
the exanthem of dengue fever: clinical features of two us tourists traveling abroad.dengue fever is the most common identifiable cause of acute febrile illness among travelers returning from south america, south central asia, southeast asia, and the caribbean. although the characteristic exanthem of dengue fever occurs in up to 50% of patients, few descriptions of it are found in the dermatology literature, and discussions of how to distinguish the dengue exanthem from other infectious disease entities are rare. chikungunya fever is an emerging infectious disease now seen in re ...200817959270
reovirus apoptosis and virulence are regulated by host cell membrane penetration efficiency.apoptosis plays an important role in the pathogenesis of reovirus encephalitis and myocarditis in infected animals. differences in apoptosis efficiency displayed by reovirus strains are linked to the viral mu1-encoding m2 gene segment. studies using pharmacologic inhibitors of reovirus replication demonstrate that apoptosis induction by reovirus requires viral disassembly in cellular endosomes but not rna synthesis. since the mu1 protein functions to pierce endosomal membranes during this tempor ...200817959662
expression of the e3l gene of vaccinia virus in transgenic mice decreases host resistance to vaccinia virus and leishmania major infections.the e3l gene of vaccinia virus (vacv) encodes the e3 protein that in cultured cells inhibits the activation of interferon (ifn)-induced proteins, double-stranded rna-dependent protein kinase (pkr), 2'-5'-oligoadenylate synthetase/rnase l (2-5a system) and adenosine deaminase (adar-1), thus helping the virus to evade host responses. here, we have characterized the in vivo e3 functions in a murine inducible cell culture system (e3l-tetoff) and in transgenic mice (tge3l). inducible e3 expression in ...200817959665
intracellular restriction of a productive noncytopathic coronavirus infection.virus infection in vitro can either result in a cytopathic effect (cpe) or proceed without visible changes in infected cells (noncytopathic infection). we are interested in understanding the mechanisms controlling the impact of coronavirus infection on host cells. to this end, we compared a productive, noncytopathic infection of murine hepatitis virus (mhv) strain a59 in the fibroblastlike cell line nih 3t3 with cytopathic mhv infections. infected nih 3t3 cells could be cultured for up to 4 week ...200817959675
viroporins from rna viruses induce caspase-dependent apoptosis.the virus-encoded viroporins are known to modify membrane permeability and play an essential role in virus budding. here, a comparative analysis of the membrane permeabilization capacity of a number of viroporins was performed in baby hamster kidney cells. synthesis of 6k protein from sindbis virus, e from mouse hepatitis virus, m2 from influenza a virus, and 2b and 3a from poliovirus enhanced membrane permeability to different extents. we show that two proteins from hepatitis c virus, p7 and ns ...200817961183
control of gag-pol gene expression in the candida albicans retrotransposon the c. albicans retrotransposon tca2, the gag and pol orfs are separated by a uga stop codon, 3' of which is a potential rna pseudoknot. it is unclear how the tca2 gag uga codon is bypassed to allow pol expression. however, in other retroelements, translational readthrough of the gag stop codon can be directed by its flanking sequence, including a 3' pseudoknot.200717961216
genistein treatment of cells inhibits arenavirus infection.arenaviridae is a family of enveloped viruses some of which are capable of causing hemorrhagic fever syndromes in humans. in this report, we demonstrate that treatment of host cells with the tyrosine kinase inhibitor genistein inhibits infection of cells with the new world arenavirus pichindé (picv). the greatest degree of inhibition was observed in pre-treated target cells, but modest inhibition of infection was also seen when drug was added to cultures up to 48h after infection. we show that p ...200817961732
recombination-ready sindbis replicon expression vectors for transgene expression.sindbis viruses have been widely used as tools to study gene function in cells. despite the utility of these systems, the construction and production of alphavirus replicons is time consuming and inefficient due to potential additional restriction sites within the insert region and lack of directionality for insert ligation. in this report, we present a system useful for producing recombinant sindbis replicons that uses lambda phage recombination technology to rapidly and specifically construct ...200717963504
antiviral properties of cobalt(iii)-complexes.we have investigated the potential antiviral activity of three cobalt(iii) compounds. two compounds, co(iii)-cyclen-methylbenzoic acid and its methyl ester derivative, are based on the macrocyclic chelator, cyclen, and were synthesized in our laboratory. both compounds have been shown to bind tightly to nucleic acids and to hydrolyze phosphodiester bonds. however, neither compound exhibited any significant antiviral activity in an in vitro model of sindbis virus replication. in contrast, a third ...200817967542
heterologous prime-boost strategy to immunize very young infants against measles: pre-clinical studies in rhesus macaques.infants in developing countries are at high risk of developing severe clinical measles if they become infected during the "window of vulnerability" (age 4-9 months), when declining maternal antibodies do not protect against wild virus, yet impede successful immunization by attenuated measles vaccine. we developed two sindbis replicon-based dna vaccines expressing measles virus hemagglutinin and fusion protein with the goal of priming young infants to respond safely and effectively to subsequent ...200717971812
recent advances in strategies for immunotherapy of human papillomavirus-induced lesions.human papillomavirus (hpv)-induced lesions are distinct in that they have targetable foreign antigens, the expression of which is necessary to maintain the cancerous phenotype. hence, they pose as a very attractive target for "proof of concept" studies in the development of therapeutic vaccines. this review will focus on the most recent clinical trials for the immunotherapy of mucosal and cutaneous hpv-induced lesions as well as emerging therapeutic strategies that have been tested in preclinica ...200817973257
the 3' untranslated region of sindbis virus represses deadenylation of viral transcripts in mosquito and mammalian cells.the positive-sense transcripts of sindbis virus (sinv) resemble cellular mrnas in that they possess a 5' cap and a 3' poly(a) tail. it is likely, therefore, that sinv rnas must successfully overcome the cytoplasmic mrna decay machinery of the cell in order to establish an efficient, productive infection. in this study, we have taken advantage of a temperature-sensitive polymerase to shut off viral transcription, and we demonstrate that sinv rnas are subject to decay during a viral infection in b ...200817977976
human immunodeficiency virus type 1 vaccine development: recent advances in the cytotoxic t-lymphocyte platform "spotty business". 200817989174
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 ...200717989181
possible stimulation of anti-tumor immunity using repeated cold stress: a hypothesis.the phenomenon of hormesis, whereby small amounts of seemingly harmful or stressful agents can be beneficial for the health and lifespan of laboratory animals has been reported in literature. in particular, there is accumulating evidence that daily brief cold stress can increase both numbers and activity of peripheral cytotoxic t lymphocytes and natural killer cells, the major effectors of adaptive and innate tumor immunity, respectively. this type of regimen (for 8 days) has been shown to impro ...200717999770
gamma-herpesvirus kinase actively initiates a dna damage response by inducing phosphorylation of h2ax to foster viral replication.dna virus infection can elicit the dna damage response in host cells, including atm kinase activation and h2ax phosphorylation. this is considered to be the host cell response to replicating viral dna. in contrast, we show that during infection of macrophages murine gamma-herpesvirus 68 (gammahv68) actively induces h2ax phosphorylation by expressing a viral kinase (orf36). gammahv68-encoded orf36 kinase and its ebv homolog, bglf4, induce h2ax phosphorylation independently of other viral genes. t ...200718005708
altered levels of stat1 and stat3 influence the neuronal response to interferon immune responses in the cns are highly regulated, cell-specific differences in ifngamma signaling may be integral in dictating the outcome of host cell responses. in comparing the response of ifngamma-treated primary neurons to control mef, we observed that neurons demonstrated lower basal expression of both stat1 and stat3, the primary signal transducers responsible for ifngamma signaling. following ifngamma treatment of these cell populations, we noted muted and delayed stat1 phosphorylatio ...200718006082
maturation-dependent responses of human neuronal cells to western equine encephalitis virus infection and type i interferons.innate cell-autonomous antiviral responses are essential first lines of defense against central nervous system infections but may also contribute to neuropathogenesis. we investigated the relationships between innate immunity and neuronal differentiation using an in vitro culture system with human cell lines to analyze cellular responses to the neurotropic alphavirus western equine encephalitis virus. human neuronal cells displayed a maturation-dependent reduction in virus-induced cytopathology ...200818022665
venezuelan equine encephalitis virus in the mosquito vector aedes taeniorhynchus: infection initiated by a small number of susceptible epithelial cells and a population bottleneck.we evaluated infection of aedes taeniorhynchus mosquitoes, vectors of venezuelan equine encephalitis virus (veev), using radiolabeled virus and replicon particles expressing green (gfp) or cherry fluorescent protein (cfp). more epidemic veev bound to and infected mosquito midguts compared to an enzootic strain, and a small number of midgut cells was preferentially infected. chimeric replicons infected midgut cells at rates comparable to those of the structural gene donor. the numbers of midgut c ...200818023837
a glur1-cgkii interaction regulates ampa receptor trafficking.trafficking of ampa receptors (ampars) is regulated by specific interactions of the subunit intracellular c-terminal domains (ctds) with other proteins, but the mechanisms involved in this process are still unclear. we have found that the glur1 ctd binds to cgmp-dependent protein kinase ii (cgkii) adjacent to the kinase catalytic site. binding of glur1 is increased when cgkii is activated by cgmp. cgkii and glur1 form a complex in the brain, and cgkii in this complex phosphorylates glur1 at s845 ...200718031684
replication-coupled packaging mechanism in positive-strand rna viruses: synchronized coexpression of functional multigenome rna components of an animal and a plant virus in nicotiana benthamiana cells by agroinfiltration.flock house virus (fhv), a bipartite rna virus of insects and a member of the nodaviridae family, shares viral replication features with the tripartite brome mosaic virus (bmv), an rna virus that infects plants and is a member of the bromoviridae family. in bmv and fhv, genome packaging is coupled to replication, a widely conserved mechanism among positive-strand rna viruses of diverse origin. to unravel the events that modulate the mechanism of replication-coupled packaging, in this study, we h ...200818032497
amino acid substitutions in the s2 subunit of mouse hepatitis virus variant v51 encode determinants of host range expansion.we previously described mouse hepatitis virus (mhv) variant v51 derived from a persistent infection of murine dbt cells with an expanded host range (r. s. baric, e. sullivan, l. hensley, b. yount, and w. chen, j. virol. 73:638-649, 1999). sequencing of the v51 spike gene, the mediator of virus entry, revealed 13 amino acid substitutions relative to the originating mhv a59 strain. seven substitutions were located in the amino-terminal s1 cleavage subunit, and six were located in the carboxy-termi ...200818032498
rotavirus infection induces the phosphorylation of eif2alpha but prevents the formation of stress granules.early during the infection process, rotavirus causes the shutoff of cell protein synthesis, with the nonstructural viral protein nsp3 playing a vital role in the phenomenon. in this work, we have found that the translation initiation factor 2alpha (eif2alpha) in infected cells becomes phosphorylated early after virus infection and remains in this state throughout the virus replication cycle, leading to a further inhibition of cell protein synthesis. under these restrictive conditions, however, t ...200818032499
bovine viral diarrhea virus core is an intrinsically disordered protein that binds rna.pestiviruses, including bovine viral diarrhea virus (bvdv), are important animal pathogens and close relatives of hepatitis c virus. pestivirus particles are composed of an rna genome, a host-derived lipid envelope, and four virion-encoded structural proteins, core (c), e(rns), e1, and e2. core is a small, highly basic polypeptide that is processed by three enzymatic cleavages before its incorporation into virions. little is known about its biological properties or its role in virion assembly an ...200818032507
uncoupling rna virus replication from transcription via the polymerase: functional and evolutionary insights.many eukaryotic positive-strand rna viruses transcribe subgenomic (sg) mrnas that are virus-derived messages that template the translation of a subset of viral proteins. currently, the premature termination (pt) mechanism of sg mrna transcription, a process thought to operate in a variety of viruses, is best understood in tombusviruses. the viral rna elements involved in regulating this mechanism have been well characterized in several systems; however, no corresponding protein factors have been ...200718034156
krüppel homolog 1 (kr-h1) mediates juvenile hormone action during metamorphosis of drosophila melanogaster.juvenile hormone (jh) given at pupariation inhibits bristle formation and causes pupal cuticle formation in the abdomen of drosophila melanogaster due to its prolongation of expression of the transcription factor broad (br). in a microarray analysis of jh-induced gene expression in abdominal integument, we found that krüppel homolog 1 (kr-h1) was up-regulated during most of adult development. quantitative real-time pcr analyses showed that kr-h1 up-regulation began at 10h after puparium formatio ...200718036785
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 ...200718054219
hippocampal poly(adp-ribose) polymerase 1 and caspase 3 activation in neonatal bornavirus infection.infection of neonatal rats with borna disease virus results in a characteristic behavioral syndrome and apoptosis of subsets of neurons in the hippocampus, cerebellum, and cortex (neonatal borna disease [nbd]). in the nbd rat hippocampus, dentate gyrus granule cells progressively degenerate. apoptotic loss of granule cells in nbd is associated with accumulation of zinc in degenerating neurons and reduced zinc in granule cell mossy fibers. excess zinc can trigger poly(adp-ribose) polymerase 1 (pa ...200818057239
the heat shock protein 70 cochaperone ydj1 is required for efficient membrane-specific flock house virus rna replication complex assembly and function in saccharomyces cerevisiae.the assembly of rna replication complexes on intracellular membranes is an essential step in the life cycle of positive-sense rna viruses. we have previously shown that hsp90 chaperone complex activity is essential for efficient flock house virus (fhv) rna replication in drosophila melanogaster s2 cells. to further explore the role of cellular chaperones in viral rna replication, we used both pharmacologic and genetic approaches to examine the role of the hsp90 and hsp70 chaperone systems in fhv ...200818057252
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