TitleAbstractYear(sorted ascending)
structure of a flavivirus envelope glycoprotein in its low-ph-induced membrane fusion conformation.enveloped viruses enter cells via a membrane fusion reaction driven by conformational changes of specific viral envelope proteins. we report here the structure of the ectodomain of the tick-borne encephalitis virus envelope glycoprotein, e, a prototypical class ii fusion protein, in its trimeric low-ph-induced conformation. we show that, in the conformational transition, the three domains of the neutral-ph form are maintained but their relative orientation is altered. similar to the postfusion c ...200414963486
aven and bcl-xl enhance protection against apoptosis for mammalian cells exposed to various culture conditions.a balance between proliferation and cell death is critical for achieving desirable high cell densities in mammalian cell culture. in this study, we evaluate a recently discovered anti-apoptotic gene, aven, and examine its effectiveness alone and in combination with a member of the bcl-2 family, bcl-xl. the commercially popular cell line, chinese hamster ovary (cho), was genetically modified to constitutively express aven, bcl-xl, and the two genes in combination. cells were exposed to several mo ...200414966800
genes encoding pir51, beclin 1, rbap48 and aldolase b are up or down-regulated in human primary hepatocellular reveal new tumor markers and target genes from differentially expressed genes of primary tumor samples using cdna microarray.200414966907
secondary structure and function of the 5'-proximal region of the equine arteritis virus rna genome.nidoviruses produce an extensive 3'-coterminal nested set of subgenomic mrnas, which are used to express their structural proteins. in addition, arterivirus and coronavirus mrnas contain a common 5' leader sequence, derived from the genomic 5' end. the joining of this leader sequence to different segments (mrna bodies) from the genomic 3'-proximal region presumably involves a unique mechanism of discontinuous minus-strand rna synthesis. key elements in this process are the so-called transcriptio ...200414970388
comparison of the transmission potential of two genetically distinct sindbis viruses after oral infection of aedes aegypti (diptera: culicidae).within mosquitoes, arboviruses encounter barriers to infection and dissemination that are critical determinants of vector competence. the molecular mechanisms responsible for these barriers have yet to be elucidated. the prototype sindbis (sin) strain, ar339, and viruses derived from this strain, such as tr339 virus, have limited infection and transmission potential in the medically important arthropod vector, aedes aegypti (l.). however, the malaysian sin virus strain, mre16, disseminates in ne ...200414989352
requirements for ceacams and cholesterol during murine coronavirus cell entry.previous reports have documented that cholesterol supplementations increase cytopathic effects in tissue culture and also intensify in vivo pathogenicities during infection by the enveloped coronavirus murine hepatitis virus (mhv). to move toward a mechanistic understanding of these phenomena, we used growth media enriched with methyl-beta-cyclodextrin or cholesterol to reduce or elevate cellular membrane sterols, respectively. cholesterol depletions reduced plaque development 2- to 20-fold, dep ...200414990688
bluetongue virus outer capsid proteins are sufficient to trigger apoptosis in mammalian cells.bluetongue virus (btv) is transmitted by culicoides sp. biting midges to livestock, causing severe hemorrhagic disease in sheep, but is asymptomatic in the insect host. similarly, btv causes rapid cell death in infected mammalian cells in culture, whereas infections of insect cells are long-term and unapparent, despite productive virus replication. to assess whether apoptosis plays any role in these two distinct cell responses, we have investigated apoptosis in cultured insect and mammalian cell ...200414990706
cholesterol is required for endocytosis and endosomal escape of adenovirus type 2.the species c adenovirus type 2 (ad2) and ad5 bind the coxsackievirus b ad receptor and alphav integrin coreceptors and enter epithelial cells by clathrin-mediated endocytosis. this pathway is rapid and efficient. it leads to cell activation and the cholesterol-dependent formation of macropinosomes. macropinosomes are triggered to release their contents when incoming ad2 escapes from endosomes. here, we show that cholesterol extraction of epithelial cells by methyl-beta-cyclodextrin (mbetacd) tr ...200414990728
development of improved sindbis virus-based dna expression vector.we have constructed an improved dna expression vector based on the sindbis virus. several dna-based sindbis virus vectors were constructed to investigate the efficiency of transgene expression. these vectors, when transfected into mammalian cells, have been used to express heterologous genes. a recombinant genome of sindbis plasmid dna, in which the structural genes were replaced by a polylinker cassette to allow for insertion of heterologous genes, was placed under the control of a simian virus ...200415000747
alphavirus vectors for cancer gene therapy (review).alphaviruses have several characteristics that make them attractive as gene therapy vectors such as transient and high-level expression of a heterologous gene. alphavirus vectors, semliki forest virus (sfv), sindbis virus (sin) and venezuelan equine encephalitis virus (vee) have been developed as gene expression vectors. alphaviruses are positive-strand rna viruses that can mediate efficient cytoplasmic gene expression in mammalian cells. the alphavirus rna replication machinery has been enginee ...200415010830
transgenic mice expressing the nucleoprotein of borna disease virus in either neurons or astrocytes: decreased susceptibility to homotypic infection and disease.the nucleoprotein (n) of borna disease virus (bdv) is the major target of the disease-inducing antiviral cd8 t-cell response in the central nervous system of mice. we established two transgenic mouse lines which express bdv-n in either neurons (neuro-n) or astrocytes (astro-n). despite strong transgene expression, neurological disease or gross behavioral abnormalities were not observed in these animals. when neuro-n mice were infected as adults, replication of bdv was severely impaired and was r ...200415016883
a peptide from autoantigen la blocks poliovirus and hepatitis c virus cap-independent translation and reveals a single tyrosine critical for la rna binding and translation, a 52-kda autoantigen in patients with systemic lupus erythematosus, was one of the first cellular proteins identified to interact with viral internal ribosome entry site (ires) elements and stimulate poliovirus (pv) and hepatitis c virus (hcv) ires-mediated translation. previous results from our laboratory have shown that a small, yeast rna (irna) could selectively inhibit pv and hcv ires-mediated translation by sequestering the la protein. here we have identified an 18-amino-acid-long seque ...200415016896
rubella virus capsid protein modulates viral genome replication and virus infectivity.the structural proteins (sp) of the togaviridae can be deleted in defective interfering rnas. the dispensability of viral sp has allowed construction of noninfectious viral expression vectors and replicons from viruses of the alphavirus and rubivirus genera. nevertheless, in this study, we found that the sp of rubella virus (rub) could enhance expression of reporter genes from rub replicons in trans. sp enhancement required capsid protein (cp) expression and was not due to rna-rna recombination. ...200415047844
glutamate receptor antagonists protect from virus-induced neural degeneration.neuronal damage during acute viral encephalomyelitis can result directly from virus infection or indirectly from the host immune response to infection. in neurodegenerative diseases and stroke, neuronal death also can result from excess release of excitatory amino acid neurotransmitters, such as glutamate. to determine the role of glutamate excitotoxicity in fatal alphavirus-induced paralytic encephalomyelitis, we treated mice infected with neuroadapted sindbis virus (nsv) with antagonists of n- ...200415048893
attenuation of sindbis virus variants incorporating uncleaved pe2 glycoprotein is correlated with attachment to cell-surface heparan sulfate.sindbis virus virions incorporating uncleaved precursor envelope protein pe2 bind efficiently to cell-surface heparan sulfate (hs) because the furin cleavage site (a consensus hs-binding domain) is retained in the mature virus particle. however, they are essentially nonviable. resuscitating mutations selected in the e3 or e2 protein preserve the pe2 noncleaving phenotype and hs binding, but facilitate fusion, and thereby restore wild-type infectivity on cultured cells. here, we have demonstrated ...200415063111
apoptosis is essential for the increased efficacy of alphaviral replicase-based dna vaccines.alphaviral replicons can increase the efficacy and immunogenicity of naked nucleic acid vaccines. to study the impact of apoptosis on this increased effectiveness, we co-delivered an anti-apoptotic gene (bcl-x(l)) with the melanocyte/melanoma differentiation antigen trp-1. although cells co-transfected with bcl-x(l) lived longer, produced more antigen and elicited increased antibody production in vivo, co-delivery of pro-survival bcl-x(l) with antigen significantly reduced the ability of the rep ...200415063579
rna interference, arthropod-borne viruses, and mosquitoes.rna interference (rnai) probably functions as an antiviral mechanism in most eukaryotic organisms. variations in the activity of this antiviral pathway in mosquitoes could explain, in part, why some mosquitoes are competent vectors of medically important, arthropod-borne viruses (arboviruses) and others are not. there are three lines of evidence that show the rnai pathway exists in aedes species that transmit arboviruses. the first is that recombinant sindbis viruses expressing a rna fragment fr ...200415068882
the human membrane cofactor cd46 is a receptor for species b adenovirus serotype 3.many human adenovirus (ad) serotypes use the coxsackie b virus-ad receptor (car). recently, cd46 was suggested to be a receptor of species b ad serotype 11 (ad11), ad14, ad16, ad21, ad35, and ad50. using sindbis virus-mediated cdna library expression, we identify here the membrane cofactor protein cd46 as a surface receptor of species b ad3. all four major cd46 transcripts and one minor cd46 transcript expressed in nucleated human cells were isolated. rodent bhk cells stably expressing the bc1 f ...200415078926
the hypervariable region 1 of the e2 glycoprotein of hepatitis c virus binds to glycosaminoglycans, but this binding does not lead to infection in a pseudotype system.the hypervariable region 1 (hvr1) of hepatitis c virus (hcv) e2 envelope glycoprotein is a 27-amino-acid sequence located at its n terminus. in this study, we investigated the functional role of hvr1 for interaction with the mammalian cell surface. the c-terminal truncated e2 glycoprotein was appended to a transmembrane domain and cytoplasmic tail of vesicular stomatitis virus (vsv) g protein for generation of the chimeric e2-g gene construct. a deletion of the hvr1 sequence from e2 was created ...200415078928
genomic analysis of the host response to hepatitis b virus infection.previous studies in hepatitis b virus (hbv)-infected humans and chimpanzees suggest that control of hbv infection involves the cells, effector functions, and molecular mediators of the immune response. the objective of the current study was to identify, in the liver of acutely hbv-infected chimpanzees, the spectrum of virus-induced and immune response-related genes that regulate the infection. the results demonstrate that hbv does not induce any genes during entry and expansion, suggesting it is ...200415100412
human cytomegalovirus causes endothelial injury through the ataxia telangiectasia mutant and p53 dna damage signaling pathways.atherosclerosis is the leading cause of death in the united states, and human cytomegalovirus (hcmv), a member of the herpes virus family, may play a role in the development of the disease. we previously showed that hcmv regulated endothelial apoptosis. in this study, we investigated the induction of apoptosis and signal transduction pathways regulating this process in hcmv-infected endothelial cells. as observed previously, hcmv induced a typical cytopathic effect in human aortic endothelial ce ...200415105295
repelling class discrimination: ephrin-a5 binds to and activates ephb2 receptor signaling.the interactions between eph receptor tyrosine kinases and their ephrin ligands regulate cell migration and axon pathfinding. the epha receptors are generally thought to become activated by ephrin-a ligands, whereas the ephb receptors interact with ephrin-b ligands. here we show that two of the most widely studied of these molecules, ephb2 and ephrin-a5, which have never been described to interact with each other, do in fact bind one another with high affinity. exposure of ephb2-expressing cells ...200415107857
changes of the secondary structure of the 5' end of the sindbis virus genome inhibit virus growth in mosquito cells and lead to accumulation of adaptive mutations.both the 5' end of the sindbis virus (sin) genome and its complement in the 3' end of the minus-strand rna synthesized during virus replication serve as parts of the promoters recognized by the enzymes that comprise the replication complex (rdrp). in addition to the 5' untranslated region (utr), which was shown to be critical for the initiation of replication, another 5' sequence element, the 51-nucleotide (nt) conserved sequence element (cse), was postulated to be important for virus replicatio ...200415113874
regional differences in viral growth and central nervous system injury correlate with apoptosis.infection of neonatal mice with reovirus t3 dearing (t3d), the prototypic neurotropic reovirus, causes fatal encephalitis associated with neuronal injury and virus-induced apoptosis throughout the brain. t3d variant k (vark) is an antigenic variant that has a nearly 1 million-fold reduction in neurovirulence following intracerebral (i.c.) inoculation compared to t3d and a restricted pattern of central nervous system injury with damage limited to the hippocampus, sparing other brain regions. we w ...200415113925
receptor-dependent coronavirus infection of dendritic several mammalian species, including humans, coronavirus infection can modulate the host immune response. we show a potential role of dendritic cells (dc) in murine coronavirus-induced immune modulation and pathogenesis by demonstrating that the jaw sii dc line and primary dc from balb/c mice and p/p mice with reduced expression of the murine coronavirus receptor, murine ceacam1a, are susceptible to murine coronavirus infection by a receptor-dependent pathway.200415113927
human immunodeficiency virus type 1 envelope glycoproteins that lack cytoplasmic domain cysteines: impact on association with membrane lipid rafts and incorporation onto budding virus particles.the human immunodeficiency virus type 1 (hiv-1) envelope comprises a surface gp120 and a transmembrane gp41. the cytoplasmic domain of gp41 contains cysteine residues (c764 and c837) which are targets for palmitoylation and were reported to be required for envelope association with lipid rafts and assembly on budding virions (i. rousso, m. b. mixon, b. k. chen, and p. s. kim, proc. natl. acad. sci. usa 97:13523-13525, 2000). several infectious hiv-1 clones contain envelopes that have no gp41 cyt ...200415113929
axonal growth of embryonic stem cell-derived motoneurons in vitro and in motoneuron-injured adult rats.we generated spinal motoneurons from embryonic stem (es) cells to determine the developmental potential of these cells in vitro and their capacity to replace motoneurons in the adult mammalian spinal cord. es cell-derived motoneurons extended long axons, formed neuromuscular junctions, and induced muscle contraction when cocultured with myoblasts. we transplanted motoneuron-committed es cells into the spinal cords of adult rats with motoneuron injury and found that approximately 3,000 es cell-de ...200415118094
persistent infection and suppression of host response by alphaviruses.alphaviruses cause chronic noncytopathic infection in mosquito cells and develop a highly cytopathic infection in a wide variety of cells of vertebrate origin. upon infection, alphaviruses modify cellular processes to meet the virus needs for propagation. downregulation of translation and transcription caused by viral infection appears to reduce interferon (ifn) and cytokine gene expression and allows more efficient dissemination of infection. alphaviruses with mutations in nonstructural protein ...200415119769
photodynamic therapy: a new antimicrobial approach to infectious disease?photodynamic therapy (pdt) employs a non-toxic dye, termed a photosensitizer (ps), and low intensity visible light which, in the presence of oxygen, combine to produce cytotoxic species. pdt has the advantage of dual selectivity, in that the ps can be targeted to its destination cell or tissue and, in addition, the illumination can be spatially directed to the lesion. pdt has previously been used to kill pathogenic microorganisms in vitro, but its use to treat infections in animal models or pati ...200415122361
poliovirus rna-dependent rna polymerase (3dpol): pre-steady-state kinetic analysis of ribonucleotide incorporation in the presence of mg2+.we have solved the complete kinetic mechanism for correct nucleotide incorporation catalyzed by the rna-dependent rna polymerase from poliovirus, 3d(pol). the phosphoryl-transfer step is flanked by two isomerization steps. the first conformational change may be related to reorientation of the triphosphate moiety of the bound nucleotide, and the second conformational change may be translocation of the enzyme into position for the next round of nucleotide incorporation. the observed rate constant ...200415122878
processing of a pestivirus protein by a cellular protease specific for light chain 3 of microtubule-associated proteins.the genome of the cytopathogenic (cp) bovine viral diarrhea virus (bvdv) jacp contains a cellular insertion coding for light chain 3 (lc3) of microtubule-associated proteins, the mammalian homologue of yeast aut7p/apg8p. the cellular insertion induces cp bvdv-specific processing of the viral polyprotein by a cellular cysteine protease homologous to the known yeast protease aut2p/apg4p. three candidate bovine protease genes were identified on the basis of the sequence similarity of their products ...200415140988
virus inactivation and protein recovery in a novel ultraviolet-c reactor.ultraviolet-c (uvc) irradiation is a viral-inactivation method that was dismissed by many plasma fractionators as a result of the potential for protein damage and the difficulty in delivering uniform doses. a reactor with novel spiral flow hydraulic mixing was recently designed for uniform and controlled uvc treatment. the objective of this study was to investigate virus inactivation and protein recovery after treatment through the new reactor.200415144527
independent functions of hsp90 in neurotransmitter release and in the continuous synaptic cycling of ampa receptors.the delivery of neurotransmitter receptors into synapses is essential for synaptic function and plasticity. in particular, ampa-type glutamate receptors (ampa receptors) reach excitatory synapses according to two distinct routes: a regulated pathway, which operates transiently during synaptic plasticity, and a constitutive pathway, which maintains synaptic function under conditions of basal transmission. however, the specific mechanisms that distinguish these two trafficking pathways are essenti ...200415152036
inhibition of reovirus by mycophenolic acid is associated with the m1 genome segment.mycophenolic acid (mpa), an inhibitor of imp dehydrogenase, inhibits reovirus replication and viral rna and protein production. in mouse l929 cells, antiviral effects were greatest at 30 microg of mpa/ml. at this dosage, mpa inhibited replication of reovirus strain t3d more than 1,000-fold and inhibited replication of reovirus strain t1l nearly 100-fold, compared to non-drug-treated controls. genetic reassortant analysis indicated the primary determinant of strain-specific differences in sensiti ...200415163710
mcp-1 and ccr2 contribute to non-lymphocyte-mediated brain disease induced by fr98 polytropic retrovirus infection in mice: role for astrocytes in retroviral neuropathogenesis.virus infection of the central nervous system (cns) often results in chemokine upregulation. although often associated with lymphocyte recruitment, increased chemokine expression is also associated with non-lymphocyte-mediated cns disease. in these instances, the effect of chemokine upregulation on neurological disease is unclear. in vitro, several chemokines including monocyte chemotactic protein 1 (mcp-1) protect neurons from apoptosis. therefore, in vivo, chemokine upregulation may be a prote ...200415163738
regulation of semliki forest virus rna replication: a model for the control of alphavirus pathogenesis in invertebrate hosts.alphavirus nonstructural proteins are translated as a polyprotein that is ultimately cleaved into four mature proteins called nsp1, nsp2, nsp3, and nsp4 from their order in the polyprotein. the role of this nonstructural polyprotein, of cleavage intermediates, and of mature proteins in synthesis of semliki forest virus (sfv) rna has been studied using mutants unable to cleave one or more of the sites in the nonstructural polyprotein or that had the arginine sense codon between nsp3 and nsp4 chan ...200415165827
neuronal apoptosis pathways in sindbis virus encephalitis.sindbis virus infects neurons of the brain and spinal cord leading to neuronal apoptosis and encephalitis in mice. during postnatal development, neurons of mice remain susceptible to infection but become refractory to sv-induced programmed cell death. failure to undergo programmed cell death results in a persistent infection. however, some neurovirulent strains of sindbis virus overcome the age-dependent protective function in neurons, leading to enhanced apoptotic cell death in the central nerv ...200415171608
identification of sympathetic premotor neurons in medullary raphe regions mediating fever and other thermoregulatory functions.sympathetic premotor neurons directly control sympathetic preganglionic neurons (spns) in the intermediolateral cell column (iml) of the thoracic spinal cord, and many of these premotor neurons are localized in the medulla oblongata. the rostral ventrolateral medulla contains premotor neurons controlling the cardiovascular conditions, whereas rostral medullary raphe regions are a candidate source of sympathetic premotor neurons for thermoregulatory functions. here, we show that these medullary r ...200415190110
regulation of synaptic strength and ampa receptor subunit composition by pick1.pick1 (protein interacting with c kinase-1) regulates the surface expression of the ampa receptor (ampar) glur2 subunit, however, the functional consequences of this interaction are not well understood. previous work has suggested that pick1 promotes the internalization of ampars. however, we found that when pick1 is virally expressed in the ca1 region of hippocampal slices, it causes an increase in ampar-mediated epsc amplitude. this effect is associated with increased ampar rectification and s ...200415190111
identification of the amino acid sequence in sindbis virus nsp4 that binds to the promoter for the synthesis of the subgenomic rna.a gel mobility-shift assay was used to demonstrate the binding of the sindbis virus transcriptase to the promoter for the synthesis of subgenomic (sg) rna. the assay made use of a p15 fraction (the cell fraction that is pelleted at 15,000 x g) from cells infected with recombinant vaccinia virions expressing various sindbis virus nonstructural proteins (nsps) and a (32)p-labeled 24-mer oligoribonucleotide representing the minimal sequence with sg promoter activity. by itself, nsp4, the viral rna- ...200415197279
endemic venezuelan equine encephalitis in northern peru.since venezuelan equine encephalitis virus (veev) was isolated in peru in 1942, >70 isolates have been obtained from mosquitoes, humans, and sylvatic mammals primarily in the amazon region. to investigate genetic relationships among the peru veev isolates and between the peru isolates and other veev strains, a fragment of the pe2 gene was amplified and analyzed by single-stranded conformation polymorphism. representatives of seven genotypes underwent sequencing and phylogenetic analysis. the res ...200415200823
causative agent of pogosta disease isolated from blood and skin lesions.pogosta disease is a mosquito-borne viral disease in finland, which is clinically manifested by rash and arthritis; larger outbreaks occur in 7-year intervals. the causative agent of the disease has been suspected of being closely related to sindbis virus (sinv). we isolated sinv from five patients with acute pogosta disease during an outbreak in fall 2002 in finland. one virus strain was recovered from a whole blood sample and four other strains from skin lesions. the etiology of pogosta diseas ...200415200824
yellow fever outbreak, imatong, southern may 2003, the world health organization received reports about a possible outbreak of a hemorrhagic disease of unknown cause in the imatong mountains of southern sudan. laboratory investigations were conducted on 28 serum samples collected from patients in the imatong region. serum samples from 13 patients were positive for immunoglobulin m antibody to flavivirus, and serum samples from 5 patients were positive by reverse transcription-polymerase chain reaction with both the genus flavivirus- ...200415207058
conformational changes in sindbis virions resulting from exposure to low ph and interactions with cells suggest that cell penetration may occur at the cell surface in the absence of membrane fusion.alphaviruses have the ability to induce cell-cell fusion after exposure to acid ph. this observation has served as an article of proof that these membrane-containing viruses infect cells by fusion of the virus membrane with a host cell membrane upon exposure to acid ph after incorporation into a cell endosome. we have investigated the requirements for the induction of virus-mediated, low ph-induced cell-cell fusion and cell-virus fusion. we have correlated the ph requirements for this process to ...200415207623
doxorubicin and paclitaxel enhance the antitumor efficacy of vaccines directed against her 2/neu in a murine mammary carcinoma model.the purpose of the present study was to determine whether cytotoxic chemotherapeutic agents administered prior to immunotherapy with gene vaccines could augment the efficacy of the vaccines.200415217493
positive effect of the hepatitis c virus nonstructural 5a protein on viral multiplication.hepatitis c virus infection (hcv), is a major cause of liver disease worldwide, and are frequently resistant to the interferon alpha treatment. the nonstructural (ns) 5a protein of hcv has been proposed to be involved in this resistance. additional studies have pointed out a role for ns5a in several other cellular interactions as well as an important role of its adaptative mutations in hcv genome replication. however, no infectious system is available to assess the role of ns5a in the hcv life c ...200415221536
bad is a pro-survival factor prior to activation of its pro-apoptotic function.the mammalian bad protein belongs to the bh3-only subgroup of the bcl-2 family. in contrast to its known pro-apoptotic function, we found that endogenous and overexpressed bad(l) can inhibit cell death in neurons and other cell types. several mechanisms regulate the conversion of bad from an anti-death to a pro-death factor, including alternative splicing that produces the n-terminally truncated bad(s). in addition, caspases convert bad(l) into a pro-death fragment that resembles the short splic ...200415231831
input- and subunit-specific ampa receptor trafficking underlying long-term potentiation at hippocampal ca3 synapses.hippocampal ca3 pyramidal neurons receive synaptic inputs from both mossy fibres (mfs) and associational fibres (afs). long-term potentiation (ltp) at these synapses differs in its induction sites and n-methyl-d-aspartate receptor (nmdar) dependence. most evidence favours the presynaptic and postsynaptic mechanisms for induction of mf ltp and af ltp, respectively. this implies that molecular and functional properties differ between mf and af synapses at both presynaptic and postsynaptic sites. i ...200415245483
the pdz domain of pick1 differentially accepts protein kinase c-alpha and glur2 as interacting ligands.the c terminus (ct) of protein kinase c-alpha (pkcalpha) has a type i pdz binding motif, whereas glur2 has a type ii pdz binding motif. both motifs are recognized by the pdz domain of protein interacting with protein kinase c (pick1), and pick1-pkcalpha-controlled phosphorylation regulates the synaptic expression and function of glur2. here, we show that a specific mutation within the carboxylate-binding loop of the pdz domain of pick1 (k27e; pick1-ke) results in a loss of interaction with glur2 ...200415247289
cytokine-mediated downregulation of coxsackievirus-adenovirus receptor in endothelial cells.endothelial cells have the ability to change their complement of cell surface proteins in response to inflammatory cytokines. we hypothesized that the expression of the coxsackievirus-adenovirus receptor (car), a viral receptor and putative cell-cell adhesion molecule, may be altered during the response of endothelial cells to inflammation. to test this hypothesis, we evaluated car protein and mrna levels in human umbilical vein endothelial cells after they were exposed to tumor necrosis factor ...200415254176
role of cd8+ t cells in control of west nile virus infection.infection with west nile virus (wnv) causes fatal encephalitis more frequently in immunocompromised humans than in those with a healthy immune system. although a complete understanding of this increased risk remains unclear, experiments with mice have begun to define how different components of the adaptive and innate immune response function to limit infection. previously, we demonstrated that components of humoral immunity, particularly immunoglobulin m (igm) and igg, have critical roles in pr ...200415254203
inactivation of west nile virus, vaccinia virus and viral surrogates for relevant and emergent viral pathogens in plasma-derived products.human plasma is the source of a wide variety of therapeutic proteins, yet it is also a potential source of viral contamination. recent outbreaks of emergent viral pathogens, such as west nile virus, and the use of live vaccinia virus as a vaccine have prompted a reassessment of the viral safety of plasma-derived products. the purpose of this study was to evaluate the efficacy of current viral inactivation methods for west nile and vaccinia viruses and to reassess the use of model viruses to pred ...200415260817
venezuelan equine encephalitis emergence: enhanced vector infection from a single amino acid substitution in the envelope 1993 and 1996, subtype ie venezuelan equine encephalitis (vee) virus caused epizootics in the mexican states of chiapas and oaxaca. previously, only subtype iab and ic vee virus strains had been associated with major outbreaks of equine and human disease. the iab and ic epizootics are believed to emerge via adaptation of enzootic (sylvatic, equine-avirulent) strains for high titer equine viremia that results in efficient infection of mosquito vectors. however, experimental equine infections w ...200415277679
pkr-dependent and -independent mechanisms are involved in translational shutoff during sindbis virus infection.the replication of sindbis virus (sin) profoundly affects the metabolism of infected vertebrate cells. one of the main events during sin infection is the strong inhibition of translation of cellular mrnas. in this study, we used a combination of approaches, including the study of sin replication in pkr(-/-) mouse embryo fibroblasts or in the presence of an excess of catalytically inactive pkr. we show that the pkr-dependent inhibition of translation is not the only and most likely not the major ...200415280454
heparan sulfate-independent infection attenuates high-neurovirulence gdvii virus-induced encephalitis.the high-neurovirulence theiler's murine encephalomyelitis virus (tmev) strain gdvii uses heparan sulfate (hs) as a coreceptor to enter target cells. we report here that gdvii virus adapted to growth in hs-deficient cells exhibited two amino acid substitutions (r3126l and n1051s) in the capsid and no longer used hs as a coreceptor. infectious-virus yields in cho cells were 25-fold higher for the adapted virus than for the parental gdvii virus, and the neurovirulence of the adapted virus in intra ...200415280499
rapid preparative purification of west nile and sindbis virus pcr products utilizing a microbore anion-exchange column.analysis and purification of specific pcr products from pcr reactions can be problematic due to several issues relating to amplification and low product yield. the use of hplc as a preparative tool in pcr product analysis is common but has not replaced traditional electrophoretic techniques for purifying dna to be used in subsequent experiments. gel purification of pcr products can result in a net loss greater than 50% of the starting dna amount. thus, this method of recovery can become the limi ...200415288956
attenuation of dengue virus infection by adeno-associated virus-mediated sirna delivery.background: the need for safe and effective treatment of dengue virus (den), a class a agent that causes dengue hemorrhagic fever/dengue shock syndrome, has been a critical global priority. an effective vaccine for den is not yet available. in this study the possibility of attenuating den infection using adeno-associated virus (aav)-encoded short interfering rnas (sirna) was examined in vero cells and human dendritic cells (dcs). methods: a cassette encoding sirna targeted to a 3' untranslated s ...200415301687
subcellular localization and calcium and ph requirements for proteolytic processing of the hendra virus fusion protein.proteolytic cleavage of the hendra virus fusion (f) protein results in the formation of disulfide-linked f1 and f2 subunits, with cleavage occurring after residue k109 in the sequence gdvk/l. this unusual cleavage site and efficient propagation of hendra virus in a furin-deficient cell line indicate that the hendra f protein is not cleaved by furin, the protease responsible for proteolytic activation of many viral fusion proteins. to identify the subcellular site of hendra f processing, vero cel ...200415308711
phototoxicity against tumor cells and sindbis virus by an octahedral rhodium bisbipyridyl complex and evidence for the genome as a target in viral octahedral rhodium complex (cis-dichloro(dipyrido[3,2a-2',3'c]phenazine)(1,10-phenanthroline)rhodium(iii) chloride; dppzphen) has been prepared that can penetrate tumor cell membranes and the sindbis viral capsid. the compound is phototoxic to these entities when irradiated with uva light. model studies with calf thymus and supercoiled plasmid dna indicate that the complex can both bind with, and nick, nucleic acid. analysis of sindbis virus, following irradiation with the metal complex, conf ...200415310216
effects of ras and rap1 on electrical excitability of differentiated ng108-15 cells.effects of two small g-proteins, rap1 and ras, on the sodium channel activity in ng108-15 cells were studied using sindbis virus-mediated gene transfer. when an activated rap1a mutant (rap1-12v, the activated mutant of rap1 carrying glycine to valine substitution at codon 12) or a dominant-negative h-ras mutant (ras-17n, carrying serine to asparagine substitution at codon 17) was expressed in differentiated ng108-15 cells, the proportion of cells generating action potential decreased and the amp ...200415312909
viral-induced spinal motor neuron death is non-cell-autonomous and involves glutamate excitotoxicity.neuroadapted sindbis virus (nsv) is a neurotropic virus capable of inducing the death of spinal motor neurons in mice and rats. in this study we investigated the mechanisms that underlie nsv-induced motor neuron death. we found that many degenerating spinal motor neurons were not infected directly with nsv, suggesting that bystander cell death occurs. an excitotoxic mechanism was confirmed when blockade of calcium-permeable ampa receptors attenuated motor neuron death both in vitro and in vivo. ...200415329404
intranasal immunization with inactivated influenza virus enhances immune responses to coadministered simian-human immunodeficiency virus-like particle antigens.intranasal immunization with inactivated influenza virus vaccine can provide protective immunity, whereas many other antigens are less effective when used for mucosal immunization. to determine whether influenza virus could enhance immune responses to an antigen coadministered to a mucosal surface, we studied the intranasal immunization of mice with a mixture of simian-human immunodeficiency virus (shiv) virus-like particles (vlps) and inactivated influenza virus. compared to mice immunized with ...200415331695
a mutant of sindbis virus which is able to replicate in cells with reduced ctp makes a replicase/transcriptase with a decreased km for ctp.we reported earlier the isolation and characterization of a sindbis virus mutant, sv(pzf), that can grow in mosquito cells treated with pyrazofurin (pzf), a compound that interferes with pyrimidine biosynthesis (y. h. lin, p. yadav, r. ravatn, and v. stollar, virology 272:61-71, 2000; y. h. lin, h. a. simmonds, and v. stollar, virology 292:78-86, 2002). three amino acid changes in nsp4, the viral rna polymerase, were required to produce this phenotype. we now describe a mutant of sindbis virus, ...200415331697
discrimination among rhinovirus serotypes for a variant icam-1 receptor molecule.intercellular adhesion molecule 1 (icam-1) is the cellular receptor for the major group of human rhinovirus serotypes, including human rhinovirus 14 (hrv14) and hrv16. a naturally occurring variant of icam-1, icam-1kilifi, has altered binding characteristics with respect to different hrv serotypes. hrv14 binds to icam-1 only transiently at physiological temperatures but forms a stable complex with icam-1kilifi. conversely, hrv16 forms a stable complex with icam-1 but does not bind to icam-1kilif ...200415331736
the immunoglobulin family member dendrite arborization and synapse maturation 1 (dasm1) controls excitatory synapse the developing mammalian brain, a large fraction of excitatory synapses initially contain only n-methyl-d-aspartate receptor and thus are "silent" at the resting membrane potential. as development progresses, synapses acquire alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (ampa-rs). although this maturation of excitatory synapses has been well characterized, the molecular basis for this developmental change is not known. here, we report that dendrite arborization and synap ...200415340156
biological diversity versus risk for mosquito nuisance and disease transmission in constructed wetlands in southern southern sweden, many wetlands have been constructed, and maintaining or increasing biological diversity is often included in the aims. some wetlands are constructed near human settlements, thus raising the problem of wetlands being associated with mosquitoes (diptera: culicidae). increased biodiversity (including mosquito diversity) is considered desirable, whereas mosquito nuisance from a human point of view is not. adult mosquito abundance, diversity and species assemblages of constructed ...200415347393
sindbis viral-mediated expression of egfp-dopamine d1 receptors in situ with real-time two-photon microscopic detection.dopamine d1 receptors (d1drs) mediate a major component of dopaminergic neurotransmission, and alterations in their synaptic and subcellular distribution may underlie a variety of neurological diseases. in order to monitor d1dr localization in real time, we subcloned a sindbis virus containing an enhanced-gfp coding region inserted at the c-terminal region of a dopamine d1 receptor (egfp-d1dr). two-photon excitation of expressed egfp-d1drs was monitored in a variety of viable neural preparations ...200415351518
zap is a crm1-dependent nucleocytoplasmic shuttling protein.the zinc finger antiviral protein (zap) is a recently isolated host antiviral factor. it specifically inhibits the replication of moloney murine leukemia virus (mmlv) and sindbis virus (sin) by preventing the accumulation of viral rna in the cytoplasm. in this report, we demonstrate that zap is predominantly localized in the cytoplasm at steady state but shuttles between the nucleus and the cytoplasm in a crm1-dependent manner. two nuclear localization sequences (nls) and one nuclear export sequ ...200415358138
human immunodeficiency virus type 1 gag-specific mucosal immunity after oral immunization with papillomavirus pseudoviruses encoding gag.mucosal surfaces are the primary portals for human immunodeficiency virus (hiv) transmission. because systemic immunization, in general, does not induce effective mucosal immune responses, a mucosal hiv vaccine is urgently needed. for this study, we developed papillomavirus pseudoviruses that express hiv-1 gag. the pseudoviruses are synthetic, nonreplicating viruses, yet they can produce antigens for a long time in the immune system. here we show that oral immunization of mice by the use of papi ...200415367590
structural properties of a multifunctional t-shaped rna domain that mediate efficient tomato bushy stunt virus rna positive-strand rna viruses, 5' untranslated regions (5' utrs) mediate many essential viral processes, including genome replication. previously, we proposed that the 5'-terminal portion of the genomic leader sequence of tomato bushy stunt virus (tbsv) forms an rna structure containing a 3-helix junction, termed the t-shaped domain (tsd). in the present study, we have carried out structure-function analysis of the proposed tsd and have confirmed an important role for this domain in mediating e ...200415367615
temporal modulation of an autoprotease is crucial for replication and pathogenicity of an rna virus.pestiviruses belong to the family flaviviridae, and their genome is a single-stranded rna of positive polarity encoding one large polyprotein which is further processed into mature proteins. noncytopathogenic (noncp) strains of the pestivirus bovine viral diarrhea virus (bvdv) can establish persistent infection. in persistently infected animals, noncp bvdvs occasionally acquire mutations in viral nonstructural protein 2 (ns2) that give rise to cytopathogenic (cp) bvdv variants, and, eventually, ...200415367643
gene therapy for malignant glioma using sindbis vectors expressing a fusogenic membrane glycoprotein.malignant glioma has a dismal prognosis. it was previously shown that glioma cells are efficiently killed when they express a gene coding for a hyperfusogenic mutant of the gibbon ape leukemia virus envelope glycoprotein (galv.fus). however, production of viral vectors expressing galv.fus has proven problematic because the transgene is toxic to vector-producing cells of human origin. we reasoned that sindbis-virus-based vectors might be ideal for galv.fus gene transfer because high-titer stocks ...200415368589
using sindbis viral vectors for specific detection and suppression of advanced ovarian cancer in animal models.we studied the therapeutic value of sindbis vectors for advanced metastatic ovarian cancer by using two highly reproducible and clinically accurate mouse models: a scid xenograft model, established by i.p. inoculation of human es-2 ovarian cancer cells, and a syngenic c57bl/6 model, established by i.p. inoculation of mouse mosec ovarian cancer cells. we demonstrate through imaging, histologic, and molecular data that sindbis vectors systemically and specifically infect/detect and kill metastasiz ...200415374985
antigenic and genetic typing of whataroa viruses in australia.we recently characterized three novel alphaviruses isolated from mosquitoes captured in new south wales, australia. initial cross-neutralization studies revealed antigenic similarity to the sindbis virus (sinv)-like whataroa virus (whav), heretofore found only in new zealand. nucleotide sequence analysis showed that the whav-like viruses shared >99% nucleotide sequence similarity with each other, and 96-97% similarity with prototype whav. enzyme-linked immunosorbent assay reactions of a panel of ...200415381803
mannose-specific plant lectins from the amaryllidaceae family qualify as efficient microbicides for prevention of human immunodeficiency virus infection.the plant lectins derived from galanthus nivalis (snowdrop) (gna) and hippeastrum hybrid (amaryllis) (hha) selectively inhibited a wide variety of human immunodeficiency virus type 1 (hiv-1) and hiv-2 strains and clinical (cxcr4- and ccr5-using) isolates in different cell types. they also efficiently inhibited infection of t lymphocytes by a variety of mutant virus strains. gna and hha markedly prevented syncytium formation between persistently infected hut-78/hiv cells and uninfected t lymphocy ...200415388446
sindbis virus--an effective targeted cancer therapeutic.viral therapies for cancer therapy have many potential positive attributes. these include the ability to specifically infect targeted cells, specifically express toxic or immune-enhancing genes, and the ability to specifically replicate within a tumor cell. despite these biological advantages, efficacy to date has been limited. a recent report demonstrates that the sindbis virus has remarkable properties in three challenging areas of gene therapy - specificity, efficacy and delivery, suggesting ...200415450742
targeted in vivo expression of proteins in the calyx of held.the calyx of held serves as a model for synaptic transmission in the mammalian central nervous system. while offering unique access to the biophysics of presynaptic function, studies addressing the molecular mechanisms of neurotransmitter exocytosis in this model have been mainly limited to pharmacological interventions. to overcome this experimental limitation we used stereotaxic delivery of viral gene shuttles to rapidly and selectively manipulate protein composition in the calyx terminal in v ...200415452710
systemic tumor targeting and killing by sindbis viral vectors.successful cancer gene therapy requires a vector that systemically and specifically targets tumor cells throughout the body. although several vectors have been developed to express cytotoxic genes via tumor-specific promoters or to selectively replicate in tumor cells, most are taken up and expressed by just a few targeted tumor cells. by contrast, we show here that blood-borne sindbis viral vectors systemically and specifically infect tumor cells. a single intraperitoneal treatment allows the v ...200414647305
heparin binding sites on ross river virus revealed by electron cryo-microscopy.cell surface glycosaminoglycans play important roles in cell adhesion and viral entry. laboratory strains of two alphaviruses, sindbis and semliki forest virus, have been shown to utilize heparan sulfate as an attachment receptor, whereas ross river virus (rrv) does not significantly interact with it. however, a single amino acid substitution at residue 218 in the rrv e2 glycoprotein adapts the virus to heparan sulfate binding and expands the host range of the virus into chicken embryo fibroblas ...200515680416
in vivo processing and isolation of furin protease-sensitive alphavirus glycoproteins: a new technique for producing mutations in virus assembly.sindbis virus particles are composed of three structural proteins (capsid/e2/e1). in the mature virion the e1 glycoprotein is organized in a highly constrained, energy-rich conformation. it is hypothesized that this energy is utilized to drive events that deliver the viral genome to the cytoplasm of a host cell. the extraction of the e1 glycoprotein from virus membranes with detergent results in disulfide-bridge rearrangement and the collapse of the protein to a number of low-energy, non-native ...200515680428
characterization of helper virus-independent cytopathogenic classical swine fever virus generated by an in vivo rna recombination system.molecular analyses revealed that most cytopathogenic (cp) pestivirus strains evolve from noncytopathogenic (noncp) viruses by nonhomologous rna recombination. in contrast to bovine viral diarrhea virus (bvdv), cp classical swine fever virus (csfv) field isolates were rarely detected and always represented helper virus-dependent subgenomes. to investigate rna recombination in more detail, we recently established an in vivo system allowing the efficient generation of recombinant cp bvdv strains in ...200515681445
proteasome inhibition protects ht22 neuronal cells from oxidative glutamate toxicity.oxidative stress caused by glutathione depletion after prolonged exposure to extracellular glutamate leads to a form of neuronal cell death that exhibits morphologically mixed features of both apoptosis and necrosis. however, specific downstream executioners involved in this form of cell death have yet to be identified. we report here that glutamate exposure does not activate caspase-3 in the ht22 neuronal cell line. furthermore, no cytoprotection was achieved with either the pan-caspase inhibit ...200515686484
subcellular localisation of recombinant alpha- and gamma-synuclein.alpha-synuclein, a protein implicated in neurodegenerative diseases and of elusive physiological function owes its name to an observed presence in presynaptic and nuclear compartments. however, its nuclear localisation has remained controversial. we expressed synuclein-egfp fusion proteins in organotypic rat hippocampal slice cultures and murine hippocampal primary neurons using a sindbis virus expression system. recombinant full-length alpha-synuclein accumulated in presynaptic locations, mimic ...200515691713
novel replicon-based reporter gene assay for detection of rubella virus in clinical specimens.proof of concept for a novel diagnostic assay for rubella virus (rub) based on rub replicons expressing reporter genes was demonstrated. rub replicons have the structural protein coding region replaced with a reporter gene such as green fluorescent protein or chloramphenicol acetyltransferase. previously, it was shown that a replicon construct with a specific in-frame deletion in the nonstructural protein coding region (noti, approximately nucleotides 1500 to 2100 of the genome) failed to replic ...200515695695
mosquitoborne viruses, czech republic, 2002.specimens from residents (n = 497) of an area affected by the 2002 flood were examined serologically for mosquitoborne viruses. antibodies were detected against tahyna (16%), sindbis (1%), and batai (0.2%) viruses, but not west nile virus. an examination of paired serum samples showed 1 tahyna bunyavirus (california group) infection.200515705333
lentiviral vector retargeting to p-glycoprotein on metastatic melanoma through intravenous injection.targeted gene transduction to specific tissues and organs through intravenous injection would be the ultimate preferred method of gene delivery. here, we report successful targeting in a living animal through intravenous injection of a lentiviral vector pseudotyped with a modified chimeric sindbis virus envelope (termed m168). m168 pseudotypes have high titer and high targeting specificity and, unlike other retroviral pseudotypes, have low nonspecific infectivity in liver and spleen. a mouse can ...200515711560
phospholipase d1-promoted release of tissue plasminogen activator facilitates neurite outgrowth.temporal lobe epilepsy (tle) is the most common form of epilepsy, affecting approximately 1-2% of the population. seizure events resulting from tle are characterized by aberrant hippocampal mossy fiber sprouting and plastic responses that affect brain function. seizure susceptibility is modulated by the enzyme tissue plasminogen activator (tpa), the normal physiological role of which includes promotion of synaptic reorganization in the mossy fiber pathway by initiating a proteolytic cascade that ...200515716416
antiviral activity of human lactoferrin: inhibition of alphavirus interaction with heparan sulfate.human lactoferrin is a component of the non-specific immune system with distinct antiviral properties. we used alphaviruses, adapted to interaction with heparan sulfate (hs), as a tool to investigate the mechanism of lactoferrin's antiviral activity. lactoferrin inhibited infection of bhk-21 cells by hs-adapted, but not by non-adapted, sindbis virus (sin) or semliki forest virus (sfv). lactoferrin also inhibited binding of radiolabeled hs-adapted viruses to bhk-21 cells or liposomes containing l ...200515721362
association of sindbis virus capsid protein with phospholipid membranes and the e2 glycoprotein: implications for alphavirus assembly.a late stage in assembly of alphaviruses within infected cells is thought to be directed by interactions between the nucleocapsid and the cytoplasmic domain of the e2 protein, a component of the viral e1/e2 glycoprotein complex that is embedded in the plasma membrane. recognition between the nucleocapsid protein and the e2 protein was explored in solution using nmr spectroscopy, as well as in binding assays using a model phospholipid membrane system that incorporated a variety of sindbis virus e ...200515723524
early expression of ampa receptors and lack of nmda receptors in developing rat climbing fibre synapses.whether nascent glutamatergic synapses acquire their ampa receptors constitutively or via a regulated pathway triggered by pre-existing nmda receptor activation is still an open issue. here, we provide evidence that some glutamatergic synapses develop without expressing nmda receptors. using immunocytochemistry, we showed that synapses between developing rat climbing fibres and purkinje cells expressed glur2-containing ampa receptors as soon as they were formed (i.e. on embryonic day 19) but nev ...200515731186
dual mechanisms of pestiviral superinfection exclusion at entry and rna replication.for many viruses, primary infection has been shown to prevent superinfection by a homologous second virus. in this study, we investigated superinfection exclusion of bovine viral diarrhea virus (bvdv), a positive-sense rna pestivirus. cells acutely infected with bvdv were protected from superinfection by homologous bvdv but not with heterologous vesicular stomatitis virus. superinfection exclusion was established within 30 to 60 min but was lost upon passaging of persistently infected cells. sup ...200515731218
characterization of an in vitro model of alphavirus infection of immature and mature neurons.terminally differentiated, mature neurons are essential cells that are not easily regenerated. neurotropic viruses, such as sindbis virus (sv), cause encephalomyelitis through their ability to replicate in neurons. sv causes the death of immature neurons, while mature neurons can often survive infection. the lack of a reproducible and convenient neuronal cell culture system has hindered a detailed study of the differences in levels of virus replication between immature and mature neurons and the ...200515731238
3'-terminal sequence in poliovirus negative-strand templates is the primary cis-acting element required for vpgpupu-primed positive-strand initiation.the 5' cloverleaf in poliovirus rna has a direct role in regulating the stability, translation, and replication of viral rna. in this study, we investigated the role of stem a in the 5' cloverleaf in regulating the stability and replication of poliovirus rna in hela s10 translation-replication reactions. our results showed that disrupting the duplex structure of stem a destabilized viral rna and inhibited efficient negative-strand synthesis. surprisingly, the duplex structure of stem a was not r ...200515731251
inhibition of viral replication by ribozyme: mutational analysis of the site and mechanism of antiviral activity.a controlled mutational study was used to determine the site and mechanism of the antiviral action of ribozymes that inhibit sindbis virus replication. a hairpin ribozyme targeting g575 of the sindbis virus genomic rna was designed and cloned into a minimized alphavirus amplicon vector. cells that were stably transfected with this construct expressed low levels of a constitutive transcript containing the ribozyme plus recognition sequences for sindbis rna replicase. upon infection, the ribozyme ...200515731266
cell type-specific targeting with sindbis pseudotyped lentiviral vectors displaying anti-ccr5 single-chain antibodies.lentiviral vectors are among the most efficient tools for gene delivery into mammalian cells. a major goal of lentiviral gene delivery systems is to develop vectors that can efficiently target specific cell types. in the present work, we attempt to generate viral particles for targeting gene delivery. we have used ccr5-positive cells as the target for our strategy. therefore, we developed a novel sindbis pseudotyped lentiviral vector where the sindbis receptor binding envelope protein was modifi ...200515761262
acid-resistant bovine pestivirus requires activation for ph-triggered fusion during entry.the route of internalization of the pestivirus bovine viral diarrhea virus (bvdv) was studied by using different chemical and biophysical inhibitors of endocytosis. expression of the dominant-negative mutant dyn(k44a) of the gtpase dynamin in mdbk cells, as well as the treatment of the cells with chlorpromazine and beta-methyl-cyclodextrin inhibited bvdv entry. bvdv infection was also abolished by potassium (k+) depletion, hyperosmolarity, and different inhibitors of endosomal acidification. we ...200515767420
identification of adult mouse neurovirulence determinants of the sindbis virus strain ar86.sindbis virus infection of mice has provided valuable insight into viral and host factors that contribute to virus-induced neurologic disease. in an effort to further define the viral genetic elements that contribute to adult mouse neurovirulence, the neurovirulent sindbis virus strain ar86 was compared to the closely related (22 single amino acid coding changes and the presence or absence of an 18-amino-acid sequence in nsp3 [positions 386 to 403]) but avirulent girdwood strain. initial studies ...200515767423
two dimensional vopba reveals laminin receptor (lamr1) interaction with dengue virus serotypes 1, 2 and 3.the search for the dengue virus receptor has generated many candidates often identified only by molecular mass. the wide host range of the viruses in vitro combined with multiple approaches to identifying the receptor(s) has led to the notion that many receptors or attachment proteins may be involved and that the different dengue virus serotypes may utilize different receptors on the same cells as well as on different cell types.200515790424
recoding elements located adjacent to a subset of eukaryal selenocysteine-specifying uga codons.incorporation of the 21st amino acid, selenocysteine, into proteins is specified in all three domains of life by dynamic translational redefinition of uga codons. in eukarya and archaea, selenocysteine insertion requires a cis-acting selenocysteine insertion sequence (secis) usually located in the 3'utr of selenoprotein mrnas. here we present comparative sequence analysis and experimental data supporting the presence of a second stop codon redefinition element located adjacent to a selenocystein ...200515791204
neuronal cell death in alphavirus encephalomyelitis.alphaviruses are mosquito-borne, enveloped, plus-strand rna viruses that cause a spectrum of diseases in humans that include fever, rash, arthritis, meningitis, and encephalomyelitis. sindbis virus (sinv) is the prototype alphavirus, causes encephalomyelitis in mice, and provides a model system for studying the pathogenesis of alphavirus-induced neurological disease. major target cells for sinv infection in the central nervous system (cns) are neurons, and both host and viral factors determine t ...200515791951
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