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a novel toll-like receptor that recognizes vesicular stomatitis virus.toll-like receptors (tlrs) are the key molecular sensors used by the mammalian innate immune system to detect various types of pathogens. tlr13 is a novel and uncharacterized member of the mammalian tlr family. here we report the cloning and characterization of tlr13. tlr13 is predominantly expressed in the spleen, particularly in dendritic cells and macrophages. tlr13 appears to activate a myd88- and tak1-dependent tlr signaling pathway, inducing the activation of nf-κb. this receptor can also ...201021131352
production of hepatitis c virus lacking the envelope-encoding genes for single-cycle infection by providing homologous envelope proteins or vesicular stomatitis virus glycoproteins in trans.hepatitis c virus (hcv) infection is a major worldwide health problem. the envelope glycoproteins are the major components of viral particles. here we developed a trans-complementation system that allows the production of infectious hcv particles in whose genome the regions encoding envelope proteins are deleted (hcvδe). the lack of envelope proteins could be efficiently complemented by the expression of homologous envelope proteins in trans. hcvδe production could be enhanced significantly by p ...201021159872
progress in filovirus vaccine development: evaluating the potential for clinical use.marburg and ebola viruses cause severe hemorrhagic fever in humans and nonhuman primates. currently, there are no effective treatments and no licensed vaccines; although a number of vaccine platforms have proven successful in animal models. the ideal filovirus vaccine candidate should be able to provide rapid protection following a single immunization, have the potential to work postexposure and be cross-reactive or multivalent against all marburg virus strains and all relevant ebola virus speci ...201121162622
synthesis and biological activity of 7h-benzo[4,5]indolo[2,3-b]-quinoxaline derivatives.new 7-(2-aminoethyl)-7h-benzo[4,5]indolo[2,3-b]quinoxalines (13-20) were synthesized with high yields starting from 3h-benzo[e]indole-1,2-dione. these compounds were screened for the cytotoxicity, anti-viral activity, interferon inducing ability and dna affinity compared with the corresponding 6-(2-aminoethyl)-6h-indolo[2,3-b]quinoxaline derivatives (1-12). it was shown, that compounds 13-20 bind to dna stronger (lg кa=6.23-6.87) than compounds 1-12 (lg кa=5.57-5.89). anti-viral activity is sign ...201021172726
access to rna encapsidated in the nucleocapsid of vesicular stomatitis virus.the genomic rna of negative-strand rna viruses, such as vesicular stomatitis virus (vsv), is completely enwrapped by the nucleocapsid protein (n) in every stage of virus infection. during viral transcription/replication, however, the genomic rna in the nucleocapsid must be accessible by the virus-encoded rna-dependent rna polymerase in order to serve as the template for rna synthesis. with the vsv nucleocapsid and a nucleocapsid-like particle (nlp) produced in escherichia coli, we have found tha ...201021177817
complementing defective viruses that express separate paramyxovirus glycoproteins provide a new vaccine vector approach.replication-defective vaccine vectors based on vesicular stomatitis virus (vsv) lacking its envelope glycoprotein gene (g) are highly effective in animal models. however, such δg vectors are difficult to grow because they require complementation with the vsv g protein. in addition, the complementing g protein induces neutralizing antibodies in animals and thus limits multiple vector applications. in the process of generating an experimental nipah virus (a paramyxovirus) vaccine, we generated two ...201021177820
genome of turbot rhabdovirus exhibits unusual non-coding regions and an additional orf that could be expressed in fish cell.genomic sequence of scophthalmus maximus rhabdovirus (smrv) isolated from diseased turbot has been characterized. the complete genome of smrv comprises 11,492 nucleotides and encodes five typical rhabdovirus genes n, p, m, g and l. in addition, two open reading frames (orf) are predicted overlapping with p gene, one upstream of p and smaller than p (temporarily called ps), and another in p gene which may encodes a protein similar to the vesicular stomatitis virus c protein. the c orf is containe ...201021185339
a functional c-terminal traf3-binding site in mavs participates in positive and negative regulation of the ifn antiviral response.recognition of viral rna structures by the cytosolic sensor retinoic acid-inducible gene-i (rig-i) results in the activation of signaling cascades that culminate with the generation of the type i interferon (ifn) antiviral response. onset of antiviral and inflammatory responses to viral pathogens necessitates the regulated spatiotemporal recruitment of signaling adapters, kinases and transcriptional proteins to the mitochondrial antiviral signaling protein (mavs). we previously demonstrated that ...201121200404
the n(0)-binding region of the vesicular stomatitis virus phosphoprotein is globally disordered but contains transient α-helices.the phosphoprotein (p) of vesicular stomatitis virus (vsv) interacts with nascent nucleoprotein (n), forming the n(0)-p complex that is indispensable for the correct encapsidation of newly synthesized viral rna genome. in this complex, the n-terminal region (p(ntr)) of p prevents n from binding to cellular rna and keeps it available for encapsidating viral rna genomes. here, using nuclear magnetic resonance (nmr) spectroscopy and small-angle x-ray scattering (saxs), we show that an isolated pept ...201121207454
distinct roles for the nf-kappa b rela subunit during antiviral innate immune responses.production of type i interferons (ifns; prominently, ifn-α/β) following virus infection is a pivotal antiviral innate immune response in higher vertebrates. the synthesis of ifn-β proceeds via the virus-induced assembly of the transcription factors irf-3/7, atf-2/c-jun, and nf-κb on the ifnβ promoter. surprisingly, recent data indicate that the nf-κb subunit rela is not essential for virus-stimulated ifnβ expression. here, we show that rela instead sustains autocrine ifn-β signaling prior to inf ...201121209118
construction and immunogenicity of a recombinant pseudotype baculovirus expressing the glycoprotein of rabies virus in mice.a pseudotype baculovirus with the glycoprotein of vesicular stomatitis virus (vsv-g) on the envelope was used as a vector for the construction of recombinant baculovirus expressing the g protein of rabies virus (rabv) under the cytomegalovirus (cmv) promoter. the generated recombinant baculovirus (bv-g) efficiently expressed the rabv g proteins in mammalian cells. intramuscular vaccination with bv-g (10(9) pfu/mouse) induced the production of rabv g-specific neutralizing antibodies and strong t ...201121221673
vesicular stomatitis virus as a vector to deliver virus-like particles of human norovirus: a new vaccine candidate against an important noncultivable virus.human norovirus (hunov) is a major causative agent of food-borne gastroenteritis worldwide. currently, there are no vaccines or effective therapeutic interventions for this virus. development of an attenuated vaccine for hunov has been hampered by the inability to grow the virus in cell culture. thus, a vector-based vaccine may be ideal. in this study, we constructed a recombinant vesicular stomatitis virus (rvsv-vp1) expressing vp1, the major capsid protein of hunov. expression of the capsid pr ...201121228240
virus infection speeds: theory versus experiment.in order to explain the speed of vesicular stomatitis virus (vsv) infections, we develop a simple model that improves previous approaches to the propagation of virus infections. for vsv infections, we find that the delay time elapsed between the adsorption of a viral particle into a cell and the release of its progeny has a very important effect. moreover, this delay time makes the adsorption rate essentially irrelevant in order to predict vsv infection speeds. numerical simulations are in agree ...201021230688
a recombinant vesicular stomatitis virus encoding hiv-1 receptors and human ox40 ligand efficiently eliminates hiv-1-infected cd4-positive t cells expressing ox40.ox40 protein is highly expressed on activated cd4-positive t cells that are susceptible for human immunodeficiency virus type 1 (hiv-1) infection. to target and kill hiv-1-infected ox40(+) t cells, we used a recombinant vesicular stomatitis virus (rvsv) lacking its envelope glycoprotein (?g) and instead expressing hiv-1 receptors cd4/cxcr4 and ox40 ligand (ox40l). expression of ox40l as well as hiv-1 receptors on the vsv particles led to specific infection of ox40(+) t cells, including primary c ...201121262309
the transmembrane domain sequence affects the structure and function of the newcastle disease virus fusion protein.the role of specific sequences in the transmembrane (tm) domain of newcastle disease virus (ndv) fusion (f) protein in the structure and function of this protein was assessed by replacing this domain with the f protein tm domains from two other paramyxoviruses, sendai virus (sv) and measles virus (mv), or the tm domain of the unrelated glycoprotein (g) of vesicular stomatitis virus (vsv). mutant proteins with the sv or mv f protein tm domains were expressed, transported to cell surfaces, and pro ...201121270151
preparation of cho cell-derived rhifn-?-fc with improved pharmacokinetics.interferon-omega (ifn-?) may be a useful, promising and alternative antiviral agent, in addition to ifn-a-2a and ifn-a-2b. to improve the pharmacokinetics of ifn-? for clinical use, the recombinant human ifn-?-fc fusion protein (rhifn-?-fc) was expressed in a chinese hamster ovary cell line (cho-s), due to the longer serum half-life of rhifn-?-fc compared to the native ifn-? protein, and purified by affinity chromatography. physicochemical characterization of the purified fusion protein was perf ...201121277904
trim56 is a virus- and interferon-inducible e3 ubiquitin ligase that restricts pestivirus infection.the tripartite motif (trim) protein family comprises more than 60 members that have diverse functions in various biological processes. although a small number of trim proteins have been shown to regulate innate immunity, much remains to be learned about the functions of the majority of the trim proteins. here we identify trim56 as a cellular protein associated with the n-terminal protease (n(pro)) of bovine viral diarrhea virus (bvdv), a pestiviral interferon antagonist which degrades interferon ...201121289118
the nlrp3 inflammasome detects encephalomyocarditis virus and vesicular stomatitis virus infection.inflammasomes are cytosolic protein complexes that regulate caspase-1 activation and the secretion of interleukin-1ß (il-1ß) and il-18. several different inflammasome complexes have been identified, but the nlrp3 inflammasome is particularly notable because of its central role in diseases of inflammation. recent work has demonstrated an essential role for the nlrp3 inflammasome in host defense against influenza virus. we show here that two other rna viruses, encephalomyocarditis virus (emcv) and ...201121289120
il-15 and type i interferon are required for activation of tumoricidal nk cells by virus-infected dendritic cells.there is increasing evidence that natural killer (nk) cells play an important role in antitumor immunity following dendritic cell (dc) vaccination. little is known, however, about the optimal stimulation of dcs that favors nk activation in tumor-bearing hosts. in this study, we demonstrate that treatment with toll-like receptor (tlr) ligands and infection with a mutant vesicular stomatitis virus (vsv-?m51) both induced dc maturation. further, inoculation of these dcs led to robust nk-mediated pr ...201121307131
[expression of goat il-18 mature protein in insect/baculovirus and determination of bioactivity of the recombinant protein].to express goat il-18 in insect/baculovirus and detect the bioactivity of the recombinant protein.201121315049
detecting protein-protein interactions in vesicular stomatitis virus using a cytoplasmic yeast two hybrid system.protein-protein interactions play an important role in many virus-encoded functions and in virus-host interactions. while a "classical" yeast two-hybrid system (y2h) is one of the most common techniques to detect such interactions, it has a number of limitations, including a requirement for the proteins of interest to be relocated to the nucleus. modified y2h, such as the sos recruitment system (srs), which detect interactions occurring in the cytoplasm rather than the nucleus, allow proteins fr ...201121320532
vesicular stomatitis virus-based h5n1 avian influenza vaccines induce potent cross-clade neutralizing antibodies in rhesus macaques.we analyzed the ability of a vaccine vector based on vesicular stomatitis virus (vsv) to induce a neutralizing antibody (nab) response to avian influenza viruses (aivs) in rhesus macaques. animals vaccinated with vectors expressing either strain a/hong kong/156/1997 or strain a/vietnam/1203/2004 h5 hemagglutinin (ha) were able to generate robust nab responses. the ability of the vectors to induce nabs against homologous and heterologous aivs after a single dose was dependent upon the ha antigen ...201121325423
consequences of conceptus exposure to colony-stimulating factor 2 on survival, elongation, interferon-t secretion, and gene expression.exposure of bovine conceptuses to colony-stimulating factor 2 (csf2) from days 5 to 7 of development can increase the percentage of transferred conceptuses that develop to term. the purpose of this experiment was to understand the mechanism by which csf2 increases embryonic and fetal survival. conceptuses were produced in vitro in the presence or absence of 10 ?ng/ml csf2 from days 5 to 7 after insemination, transferred into cows, and flushed from the uterus at day 15 of pregnancy. there was a t ...201121339286
hiv-1 requires arf6-mediated membrane dynamics to efficiently enter and infect t lymphocytes.as the initial barrier to viral entry, the plasma membrane along with the membrane trafficking machinery and cytoskeleton are of fundamental importance in the viral cycle. however, little is known about the contribution of plasma membrane dynamics during early human immunodeficiency virus type 1 (hiv-1) infection. considering that adp ribosylation factor 6 (arf6) regulates cellular invasion via several microorganisms by coordinating membrane trafficking, our aim was to study the function of arf6 ...201121346189
partial efficacy of a vsv-siv/mva-siv vaccine regimen against oral siv challenge in infant macaques.despite antiretroviral medications, the rate of pediatric hiv-1 infections through breast-milk transmission has been staggering in developing countries. therefore, the development of a vaccine to protect vulnerable infant populations should be actively pursued. we previously demonstrated that oral immunization of newborn macaques with vesicular stomatitis virus expressing simian immunodeficiency virus genes (vsv-siv) followed 2 weeks later by an intramuscular boost with modified vaccinia ankara ...201121377510
enhancing vsv oncolytic activity with an improved cytosine deaminase suicide gene strategy.oncolytic viruses (ovs) are promising therapeutic agents for cancer treatment, with recent studies emphasizing the combined use of chemotherapeutic compounds and prodrug suicide gene strategies to improve ov efficacy. in the present study, the synergistic activity of recombinant vesicular stomatitis virus (vsv)-m+ö51 virus expressing the cytosine deaminase/uracil phosphoribosyltransferase (cd::uprt) suicide gene and 5-fluorocytosine (5fc) prodrug was investigated in triggering tumor cell oncolys ...201121394109
medical microbiologythe family rhabdoviridae consists of more than 100 single-stranded, negative-sense, nonsegmented viruses that infect a wide variety of hosts, including vertebrates, invertebrates, and plants. common to all members of the family is a distinctive rod- or bullet-shaped morphology. human pathogens of medical importance are found in the genera lyssavirus and vesiculovirus.only rabies virus, medically the most significant member of the genus lyssavirus, is reviewed in this chapter.199621413354
possible role of phosphoinositide-3-kinase in mx1 protein translation and antiviral activity of interferon-omega-stimulated hela cells.interferon ? (ifn-?), a cytokine released during innate immune activation, is well known for promoting direct antiviral responses; however, the possible signal pathways that are initiated by ifn-? binding to the type i ifn receptors have not been fully studied. here, we provide evidence that activation of phosphoinositide-3-kinase/protein kinase b (pi3k/akt) signaling plays a pivotal role in the generation of ifn-?-mediated biological responses. we found that ly294002 (pi3k inhibitor)-attenuated ...201121430412
rnai screening for host factors involved in viral infection using drosophila cells.since viral pathogens represent a significant threat to human health, a better understanding of the cellular factors that impact infection would facilitate the development of therapeutics. the recent advent of rna interference (rnai) technology coupled with the ease and efficiency of rnai in drosophila cell culture has led to the widespread use of this experimental system for high-throughput rnai screening of host factors required for viral infection [cherry et al., genes dev 19:445-452, 2005; h ...201121431698
oncolytic vesicular stomatitis virus administered by isolated limb perfusion suppresses osteosarcoma growth.a significant limitation to oncolytic virotherapy in vivo is the lack of a clinically relevant means of delivering the virus. we evaluated the oncolytic activity of vesicular stomatitis virus (vsv) in human osteosarcoma cells and explored isolated limb perfusion (ilp) as a novel oncolytic virus delivery system to extremity sarcoma in immune-competent rats. human and rat osteosarcoma cells transduced with rvsv-lacz uniformly expressed β-gal. vsv was fully capable of replicating its rna genome in ...201121437961
viral infection induces thymic stromal lymphopoietin (tslp) in human keratinocytes. 201121440421
inactivation of a human norovirus surrogate, human norovirus virus-like particles, and vesicular stomatitis virus by gamma irradiation.gamma irradiation is a nonthermal processing technology that has been used for the preservation of a variety of food products. this technology has been shown to effectively inactivate bacterial pathogens. currently, the fda has approved doses of up to 4.0 kgy to control food-borne pathogens in fresh iceberg lettuce and spinach. however, whether this dose range effectively inactivates food-borne viruses is less understood. we have performed a systematic study on the inactivation of a human norovi ...201121441330
pseudotyping vesicular stomatitis virus with lymphocytic choriomeningitis virus glycoproteins enhances infectivity for glioma cells and minimizes neurotropism.vesicular stomatitis virus (vsv)-based oncolytic virotherapy has the potential to significantly improve the prognosis of aggressive malignancies such as brain cancer. however, vsv's inherent neurotoxicity has hindered clinical development so far. given that this neurotropism is attributed to the glycoprotein vsv-g, vsv was pseudotyped with the nonneurotropic envelope glycoprotein of the lymphocytic choriomeningitis virus (lcmv-gp?vsv-gp). compared to vsv, vsv-gp showed enhanced infectivity for b ...201121450833
cross-dressed dendritic cells drive memory cd8+ t-cell activation after viral infection.after an infection, cytotoxic t lymphocyte precursors proliferate and become effector cells by recognizing foreign peptides in the groove of major histocompatibility complex (mhc) class i molecules expressed by antigen-presenting cells (apcs). professional apcs specialized for t-cell activation acquire viral antigen either by becoming infected themselves (direct presentation) or by phagocytosis of infected cells, followed by transfer of antigen to the cytosol, processing and mhc class i loading ...201121455179
vesicular stomatitis virus-simian retrovirus type 2 vaccine protects macaques from detectable infection and b-cell destruction.natural infection with simian retrovirus (srv) has long been recognized in rhesus macaques (rms) and may result in an aids-like disease. importantly, srv infections persist as a problem in recently imported macaques. therefore, there is a clear need to control srv spread in macaque colonies. we developed a recombinant vesicular stomatitis virus (vsv)-srv vaccine consisting of replication-competent hybrid vsvs that express srv gag and env in separate vectors. the goal of this study was to assess ...201121490096
the stochastic quasi-steady-state assumption: reducing the model but not the noise.highly reactive species at small copy numbers play an important role in many biological reaction networks. we have described previously how these species can be removed from reaction networks using stochastic quasi-steady-state singular perturbation analysis (sqspa). in this paper we apply sqspa to three published biological models: the pap operon regulation, a biochemical oscillator, and an intracellular viral infection. these examples demonstrate three different potential benefits of sqspa. fi ...201121513377
role of p38 protein kinase in the ligand-independent ubiquitination and downregulation of the ifnar1 chain of type i interferon receptor.phosphorylation-dependent ubiquitination and degradation of the ifnar1 chain of type i interferon (ifn) receptor is a robust and specific mechanism that limits the magnitude and duration of ifnα/β signaling. besides the ligand-inducible ifnar1 degradation, the existence of an inside-out signaling that accelerates ifnar1 turnover in the cells undergoing the endoplasmic reticulum (er) stress and activated unfolded protein responses (upr) has been recently described. the latter pathway does not req ...201121540188
development of an inactivated candidate vaccine against chandipura virus (rhabdoviridae: vesiculovirus).a vero cell based vaccine candidate against chandipura (chp) virus (rhabdoviridae: vesiculovirus), was developed and evaluated for immunogenicity in mice. virus was purified by ultracentrifugation on 30% glycerol cushion followed by differential centrifugation on 10-60% sucrose gradient and inactivated with β-propio lactone at a concentration of 1:3500. the inactivated product was blended with aluminium phosphate (3%) and immunized 4-week-old swiss albino mice. neutralizing antibodies in the ran ...201121549791
proteomic analyses of gastric cancer cells treated with vesicular stomatitis virus matrix protein.gastric cancer constitutes the second leading cause of mortality worldwide and the fourth most common cancer. while chemotherapy remains the primary treatment for both resectable and advanced gastric cancer, most gastric cancers are naturally resistant to anticancer drugs, rendering new therapeutic avenues in dire need. vesicular stomatitis virus (vsv) was proved to preferentially replicate in many types of tumor cells and eventually induce apoptosis of host cells. the vesicular stomatitis virus ...201121574062
the protease-sensitive loop of the vesicular stomatitis virus matrix protein is involved in virus assembly and protein translation.to study the contribution of the protease-sensitive loop of the vsv m protein in virus assembly we recovered recombinant vsv (rvsv) with mutations in this region and examined virus replication. mutations in the highly conserved lxd motif (aa 123-125) resulted in reduced virion budding, reduced virus titers and enhanced m protein exchange with m-ribonucleocapsid complexes (m-rnps), suggesting that the mutant m proteins were less tightly associated with rnp skeletons. in addition, viral protein sy ...201121596416
immune regulation in chandipura virus infection: characterization of cd4+ t regulatory cells from infected mice.abstract: back ground: chandipura virus produces acute infection in mice. during infection drastic reduction of cd4+, cd8+ and cd19 + cell was noticed. depletion of lymphocytes also noticed in spleen. the reduction may be due to the regulatory mechanism of immune system to prevent the bystander host tissue injury. there are several mechanisms like generation of regulatory cells, activation induced cell death (acid) etc were indicated to control the activation and maintain cellular homeostasis. r ...201121612593
hiv-protease inhibitors block the replication of both vesicular stomatitis and influenza viruses at an early post-entry replication step.the inhibitors of hiv-1 protease (pis) have been designed to block the activity of the viral aspartyl-protease. however, it is now accepted that this family of inhibitors can also affect the activity of cell proteases. since the replication of many virus species requires the activity of host cell proteases, investigating the effects of pis on the life cycle of viruses other than hiv would be of interest. here, the potent inhibition induced by saquinavir and nelfinavir on the replication of both ...201121620431
host response to polyoma virus infection is modulated by rna adenosine deaminase adar1 but not by adar2.adenosine deaminases acting on rna (adars) catalyze the c-6 deamination of adenosine (a) to produce inosine (i) which behaves as guanine (g), thereby altering base pairing in rnas with double-stranded character. two genes, adar1 and adar2, are known to encode enzymatically active adars in mammalian cells. furthermore, two size forms of adar1 are expressed by alternative promoter usage, a short (p110) nuclear form that is constitutively made and a long (p150) form that is interferon-inducible and ...201121632755
a freeze frame view of vesicular stomatitis virus transcription defines a minimal length of rna for 5' processing.the rna synthesis machinery of vesicular stomatitis virus (vsv) comprises the genomic rna encapsidated by the viral nucleocapsid protein (n) and associated with the rna dependent rna polymerase, the viral components of which are a large protein (l) and an accessory phosphoprotein (p). the 241 kda l protein contains all the enzymatic activities necessary for synthesis of the viral mrnas, including capping, cap methylation and polyadenylation. those rna processing reactions are intimately coordina ...201121655110
differential, type i interferon-mediated autophagic trafficking of hepatitis c virus proteins in mouse liver.the hepatitis c virus (hcv) serine protease ns3/4a can cleave mitochondria-associated antiviral signaling protein (mavs) and block retinoic acid-inducible gene i-mediated interferon (ifn) responses. although this mechanism is thought to have an important role in hcv-mediated innate immunosuppression, its significance in viral persistence is not clear.201121683701
broad antigenic coverage induced by vaccination with virus-based cdna libraries cures established tumors.effective cancer immunotherapy requires the release of a broad spectrum of tumor antigens in the context of potent immune activation. we show here that a cdna library of normal tissue, expressed from a highly immunogenic viral platform, cures established tumors of the same histological type from which the cdna library was derived. immune escape occurred with suboptimal vaccination, but tumor cells that escaped the immune pressure were readily treated by second-line virus-based immunotherapy. thi ...201121685898
reverse genetics system for chandipura virus: tagging the viral matrix protein with green fluorescent protein.chandipura virus (cv; genus vesiculovirus, family rhabdoviridae) is an emerging arbovirus, responsible for a number of outbreaks of severe viral encephalitis affecting children in india. a reverse genetics system has been constructed which allows recovery of infectious recombinant cv (rcv) entirely from cdna. this system was used to construct a virus, rcve, which has an additional transcription unit encoding green fluorescent protein (egfp) between the 3rd and 4th cv genes. this virus grew to ti ...201121704089
ck2 inhibitors increase the sensitivity of hsv-1 to interferon-+¦.herpes simplex virus type 1 (hsv-1) requires the activities of cellular kinases for efficient replication. the host kinase, ck2, has been shown or is predicted to modify several hsv-1 proteins and has been proposed to affect one or more steps in the viral life cycle. furthermore, potential cellular and viral substrates of ck2 are involved in antiviral pathways and viral counter-defenses, respectively, suggesting that ck2 regulates these processes. consequently, we tested whether pharmacological ...201121722672
vesicular stomatitis virus has extensive oncolytic activity against human sarcomas: rare resistance is overcome by blocking interferon pathways.oncolytic viruses have been tested against many carcinomas of ectodermal and endodermal origin; however, sarcomas, arising from mesoderm, have received relatively little attention. using 13 human sarcomas representing seven tumor types, we assessed the efficiency of infection, cytolysis, and replication of green fluorescent protein (gfp)-expressing vesicular stomatitis virus (vsv) and its oncolytically enhanced mutant vsv-rp30a. both viruses efficiently infected and killed 12 of 13 sarcomas. vsv ...201121734048
a viral strategy to ambush tumors. 201121738155
Involvement of Noxa in mediating cellular ER stress responses to lytic virus infection.Noxa is a Bcl-2 homology domain-containing pro-apoptotic mitochondrial protein. Noxa mRNA and protein expression are upregulated by dsRNA or virus, and ectopic Noxa expression enhances cellular sensitivity to virus or dsRNA-induced apoptosis. Here we demonstrate that Noxa null baby mouse kidney (BMK) cells are deficient in normal cytopathic response to lytic viruses, and that reconstitution of the knockout cells with wild-type Noxa restored normal cytopathic responses. Noxa regulation by virus m ...201121742363
protein transfer into human cells by vsv-g-induced nanovesicles.identification of new techniques to express proteins into mammal cells is of particular interest for both research and medical purposes. the present study describes the use of engineered vesicles to deliver exogenous proteins into human cells. we show that overexpression of the spike glycoprotein of the vesicular stomatitis virus (vsv-g) in human cells induces the release of fusogenic vesicles named gesicles. biochemical and functional studies revealed that gesicles incorporated proteins from pr ...201121750535
antagonistic effects of cellular poly(c) binding proteins on vesicular stomatitis virus gene expression.immunoprecipitation and subsequent mass-spectrometric analysis of the cellular proteins from cells expressing the vsv p protein identified the poly(c) binding protein 2 (pcbp2) as one of the p protein interacting protein. to investigate the role of pcbp2 in the viral life cycle, we examined the effects of depletion or overexpression of this protein on vsv growth. sirna-mediated silencing of pcbp2 promoted vsv replication. conversely, overexpression of pcbp2 in transfected cells suppressed vsv gr ...201121752917
human immunodeficiency virus type 1 induces lytic cycle replication of kaposi's-sarcoma-associated herpesvirus: role of ras/c-raf/mek1/2, pi3k/akt, and nf-?b signaling pathways.human immunodeficiency virus type 1 (hiv-1) infection significantly increases the risk and development of kaposi's sarcoma (ks) in individuals infected with ks-associated herpesvirus (kshv). previously, we reported that hiv-1 tat protein induced kshv replication by modulating the janus kinase/signal transducers and activators of transcription signaling pathway. here, we further investigated the possible signaling pathways involved in hiv-1-induced reactivation of kshv. we showed that hiv-1 infec ...201121763505
the alpha subunit of eukaryotic initiation factor (eif) 2b is requisite for eif2-mediated translational suppression of vesicular stomatitis virus.eukaryotic translation initiation factor 2b (eif2b) is a heteropentameric guanine nucleotide exchange factor that converts protein synthesis initiation factor 2 (eif2) from a gdp-bound form to the active eif2-gtp complex. cellular stress can repress translation initiation by activating kinases capable of phosphorylating the alpha subunit of eif2, which sequesters eif2b to prevent exchange activity. previously, we have demonstrated that tumor cells are sensitive to viral replication, plausibly du ...201121795329
interferon impedes an early step of hepatitis delta virus infection.hepatitis delta virus (hdv) infects hepatocytes, the major cell type of the liver. infection of the liver may be either transient or chronic. the prognosis for patients with chronic hdv infection is poor, with a high risk of cirrhosis and hepatocellular carcinoma. the best antiviral therapy is weekly administration for at least one year of high doses of interferon alpha. this efficacy of interferon therapy has been puzzling in that hdv replication in transfected cell lines is reported as insensi ...201121811602
vesicular stomatitis virus (vsv) expressing tumor suppressor p53 is a highly attenuated, potent oncolytic agent.vesicular stomatitis virus (vsv), a negative stranded rna rhabdovirus, preferentially replicates in and eradicates transformed versus non-transformed cells, and is thus being considered for use as a potential anti-cancer treatment. the genetic malleability of vsv also affords an opportunity to develop more potent agents that exhibit increased therapeutic activity. the tumor suppressor p53 has been shown to exert potent anti-tumor properties, which may in part involve stimulating host innate immu ...201121813611
anterograde or retrograde transsynaptic labeling of cns neurons with vesicular stomatitis virus vectors.to understand how the nervous system processes information, a map of the connections among neurons would be of great benefit. here we describe the use of vesicular stomatitis virus (vsv) for tracing neuronal connections in vivo. we made vsv vectors that used glycoprotein (g) genes from several other viruses. the g protein from lymphocytic choriomeningitis virus endowed vsv with the ability to spread transsynaptically, specifically in an anterograde direction, whereas the rabies virus glycoprotei ...201121825165
genetic and antigenic relationships of vesicular stomatitis viruses from south america.vesicular stomatitis (vs) viruses have been classified into two serotypes: new jersey (vsnjv) and indiana (vsiv). here, we have characterized field isolates causing vesicular stomatitis in brazil and argentina over a 35-year span. cluster analysis based on either serological relatedness, as inferred from virus neutralization and complement fixation assays, or nucleotide sequences of two separate genes (phosphoprotein or glycoprotein) grouped the field isolates into two distinct monophyletic grou ...201121830071
natural resistance-associated macrophage protein is a cellular receptor for sindbis virus in both insect and mammalian hosts.alphaviruses, including several emerging human pathogens, are a large family of mosquito-borne viruses with sindbis virus being a prototypical member of the genus. the host factor requirements and receptors for entry of this class of viruses remain obscure. using a drosophila system, we identified the divalent metal ion transporter natural resistance-associated macrophage protein (nramp) as a host cell surface molecule required for sindbis virus binding and entry into drosophila cells. consequen ...201121843867
first detection of pike fry-like rhabdovirus in barbel and spring viraemia of carp virus in sturgeon and pike in aquaculture in the czech republic.rapid antigen detection enzyme-linked immunosorbent assay (elisa) testing of cell cultures with organ homogenate from fish, collected from farms with a predominance of common carp or in natural aquaculture in the czech republic between 1995 and 2008, identified piscine vesiculovirus in 27 of 178 samples. using reverse transcription semi-nested pcr, targeting a 550 nucleotide region of the glycoprotein (g) gene, piscine vesiculovirus was confirmed in 23 of the 27 organ samples diagnosed by elisa ...201121848117
the ebola virus glycoprotein mediates entry via a non-classical dynamin-dependent macropinocytic pathway.ebola virus (ebov) has been reported to enter cultured cell lines via a dynamin-2-independent macropinocytic pathway or clathrin-mediated endocytosis. the route(s) of productive ebov internalization into physiologically relevant cell types remain unexplored, and viral-host requirements for this process are incompletely understood. here, we use electron microscopy and complementary chemical and genetic approaches to demonstrate that the viral glycoprotein, gp, induces macropinocytic uptake of vir ...201121907381
chemical inhibition of rna viruses reveals redd1 as a host defense factor.a chemical genetics approach was taken to identify inhibitors of ns1, a major influenza a virus virulence factor that inhibits host gene expression. a high-throughput screen of 200,000 synthetic compounds identified small molecules that reversed ns1-mediated inhibition of host gene expression. a counterscreen for suppression of influenza virus cytotoxicity identified naphthalimides that inhibited replication of influenza virus and vesicular stomatitis virus (vsv). the mechanism of action occurs ...201121909097
neural circuits look forward. 201121914847
genetic diversity of perch rhabdoviruses isolates based on the nucleoprotein and glycoprotein genes.despite the increasing impact of rhabdoviruses in european percid farming, the diversity of the viral populations is still poorly investigated. to address this issue, we sequenced the partial nucleoprotein (n) and complete glycoprotein (g) genes of nine rhabdoviruses isolated from perch (perca fluviatilis) between 1999 and 2010, mostly from france, and analyzed six of them by immunofluorescence antibody test (ifat). using two rabbit antisera raised against either the reference perch rhabdovirus ...201121927897
E-cadherin promotes accumulation of a unique memory CD8 T-cell population in murine salivary glands.The salivary glands are important effector sites for IgA-mediated humoral immunity to protect oral surfaces. Within murine submandibular glands (SMG), we identified a memory CD8 T-cell population that exhibited a unique cell-surface phenotype distinct from memory CD8 T cells in spleen but similar to memory T cells resident in the intraepithelial lymphocyte compartment of the intestinal mucosa. In mice immune to lymphocytic choriomeningitis virus (LCMV) or vesicular stomatitis virus(VSV), virus-s ...201121930933
propagation, purification, and in vivo testing of oncolytic vesicular stomatitis virus strains.oncolytic viruses are self-amplifying therapeutics that specifically replicate in and kill cancer cells. we have previously shown that vesicular stomatitis virus (vsv) can be used as an oncolytic virus. a strain of vsv harboring a mutation in the m protein (vsvδ51) was found to exhibit enhanced tumor selectivity over its wild-type counterpart due to its inability to overcome antiviral programs in normal cells and due to the frequent defects in antiviral signaling pathways observed in the majorit ...201221948474
Structure of the vesicular stomatitis virus N°-P complex.Replication of non-segmented negative-strand RNA viruses requires the continuous supply of the nucleoprotein (N) in the form of a complex with the phosphoprotein (P). Here, we present the structural characterization of a soluble, heterodimeric complex between a variant of vesicular stomatitis virus N lacking its 21 N-terminal residues (N(?21)) and a peptide of 60 amino acids (P(60)) encompassing the molecular recognition element (MoRE) of P that binds RNA-free N (N(0)). The complex crystallized ...201121960769
[Development of viral vectors and application for viral entry mechanisms].Virus is identified as one of the obligate intracellular parasites, which only amplify in cells of specific living things. Viral vectors, which are developed by utilizing these properties, are available in the various fields such as basic research of medical biology or application of gene therapy. Our research group has studied development of viral vectors using properties of baculovirus or vesicular stomatitis virus (VSV). Due to the development of new baculoviral vectors for mammalian cells, i ...201121972561
vesicular stomatitis virus-based ebola vaccines with improved cross-protective efficacy.for ebola virus (ebov), 4 different species are known: zaire, sudan, côte d'ivoire, and reston ebolavirus. the newly discovered bundibugyo ebolavirus has been proposed as a 5th species. so far, no cross-neutralization among ebov species has been described, aggravating progress toward cross-species protective vaccines. with the use of recombinant vesicular stomatitis virus (rvsv)-based vaccines, guinea pigs could be protected against zaire ebolavirus (zebov) infection only when immunized with a v ...201121987743
Recombinant vesicular stomatitis virus-based vaccines against Ebola and Marburg virus infections.The filoviruses, Marburg virus and Ebola virus, cause severe hemorrhagic fever with a high mortality rate in humans and nonhuman primates. Among the most-promising filovirus vaccines under development is a system based on recombinant vesicular stomatitis virus (rVSV) that expresses a single filovirus glycoprotein (GP) in place of the VSV glycoprotein (G). Importantly, a single injection of blended rVSV-based filovirus vaccines was shown to completely protect nonhuman primates against Marburg vir ...201121987744
single immunization with a monovalent vesicular stomatitis virus-based vaccine protects nonhuman primates against heterologous challenge with bundibugyo ebolavirus.the recombinant vesicular stomatitis virus (rvsv) vector-based monovalent vaccine platform expressing a filovirus glycoprotein has been demonstrated to provide protection from lethal challenge with ebola (ebov) and marburg (marv) viruses both prophylactically and after exposure. this platform provides protection between heterologous strains within a species; however, protection from lethal challenge between species has been largely unsuccessful. to determine whether the rvsv-ebov vaccines have t ...201121987745
protective efficacy of a bivalent recombinant vesicular stomatitis virus vaccine in the syrian hamster model of lethal ebola virus infection.outbreaks of filoviral hemorrhagic fever occur sporadically and unpredictably across wide regions in central africa and overlap with the occurrence of other infectious diseases of public health importance.201121987746
management of accidental exposure to ebola virus in the biosafety level 4 laboratory, hamburg, germany.a needlestick injury occurred during an animal experiment in the biosafety level 4 laboratory in hamburg, germany, in march 2009. the syringe contained zaire ebolavirus (zebov) mixed with freund's adjuvant. neither an approved treatment nor a postexposure prophylaxis (pep) exists for ebola hemorrhagic fever. following a risk-benefit assessment, it was recommended the exposed person take an experimental vaccine that had shown pep efficacy in zebov-infected nonhuman primates (nhps) [12]. the vacci ...201121987751
permissivity of the nci-60 cancer cell lines to oncolytic vaccinia virus glv-1h68.oncolytic viral therapy represents an alternative therapeutic strategy for the treatment of cancer. we previously described glv-1h68, a modified vaccinia virus with exclusive tropism for tumor cells, and we observed a cell line-specific relationship between the ability of glv-1h68 to replicate in vitro and its ability to colonize and eliminate tumor in vivo.201122011439
whole genomes of chandipura virus isolates and comparative analysis with other rhabdoviruses.the chandipura virus (chpv) belonging to the vesiculovirus genus and rhabdoviridae family, has recently been associated with a number of encephalitis epidemics, with high mortality in children, in different parts of india. no full length genome sequences of chpv isolates were available in genbank and little is known about the molecular markers for pathogenesis. in the present study, we provide the complete genomic sequences of four isolates from epidemics during 2003-2007. these sequences along ...201222272333
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