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a let-7 microrna-sensitive vesicular stomatitis virus demonstrates tumor-specific replication.creation of potent oncolytic viruses (ovs) suitable for the clinic may require new strategies in virus design. replication-competent viruses facilitate a variety of approaches to achieving tumor specificity. altered expression of micrornas is a common hallmark of cancer that we demonstrate can be used to alter expression of a potent wild-type viral gene to achieve tumor-specific replication of an engineered vesicular stomatitis virus (vsv). incorporation of let-7 microrna complementary sequences ...200818560417
length-dependent recognition of double-stranded ribonucleic acids by retinoic acid-inducible gene-i and melanoma differentiation-associated gene 5.the ribonucleic acid (rna) helicases retinoic acid-inducible gene-i (rig-i) and melanoma differentiation-associated gene 5 (mda5) recognize distinct viral and synthetic rnas, leading to the production of interferons. although 5'-triphosphate single-stranded rna is a rig-i ligand, the role of rig-i and mda5 in double-stranded (ds) rna recognition remains to be characterized. in this study, we show that the length of dsrna is important for differential recognition by rig-i and mda5. the mda5 ligan ...200818591409
differential recognition of double-stranded rna by rig-i-like receptors in antiviral immunity.retinoic acid-inducible gene (rig)-i-like receptors (rlrs) are cytosolic rna helicases that sense viral rna and trigger signaling pathways that induce the production of type i interferons (ifns) and proinflammatory cytokines. rlrs recognize distinct and overlapping sets of viruses, but the mechanisms that dictate this specificity were unknown. a new study now provides evidence for size-based discrimination of double-stranded rna (dsrna) by rlrs and suggests how host cells recognize a variety of ...200818591413
development and evaluation of a one-step loop-mediated isothermal amplification for detection of spring viraemia of carp virus.spring viraemia of carp virus (svcv) is the causative agent of svc disease. the main aim of our study was to develop a one-step reverse transcription loop-mediated isothermal amplification (rt-lamp) assay for rapid, sensitive and effective detection of svcv.200818631262
antagonistic pleiotropy involving promoter sequences in a virus.selection of specialist genotypes, that is, populations with limited niche width, promotes the maintenance of diversity. specialization to a particular environment may have a cost in other environments, including fitness tradeoffs. when the tradeoffs are the result of mutations that have a beneficial effect in the selective environment but a deleterious effect in other environments, we have antagonistic pleiotropy. alternatively, tradeoffs can result from the fixation of mutations that are neutr ...200818644381
antibody-mediated enhancement of the rate, magnitude, and responsiveness of vesicular stomatitis virus induced alpha interferon production.a majority of adults without evidence of exposure to vesicular stomatitis virus (vsv) have serum igg antibodies that interact with pro-inflammatory tlr7 in the presence of vsv, and enhance several aspects of vsv-induced ifn-alpha production. enhancing igg antibody enables human pbmc to make ifn-alpha more rapidly and in higher titers in response to a broad range of vsv-concentrations that include those too low to independently stimulate ifn-alpha production. these antibody-mediated functions com ...200818649334
efficacy of systemically administered mutant vesicular stomatitis virus (vsvdelta51) combined with radiation for nasopharyngeal carcinoma.nasopharyngeal carcinoma (npc) is a malignancy of the head and neck region that is associated with ebv latency. curative treatments for npc achieve modest survival rates, underscoring a need to develop novel therapies. we evaluated the therapeutic potential of a mutant vesicular stomatitis virus (vsvdelta51) as single treatment modality or in combination with ionizing radiation (rt) in npc.200818676763
the eif2alpha kinases inhibit vesicular stomatitis virus replication independently of eif2alpha phosphorylation.the eif2alpha kinases have been involved in the inhibition of vesicular stomatatis virus replication but the contribution of each kinase to this process has not been fully investigated. using mouse embryonic fibroblasts (mefs) from knock-out mice we show that pkr and hri have no effects on vsv replication as opposed to perk and gcn2, which exhibit strong inhibitory effects. when mefs containing the serine 51 to alanine mutation of eif2alpha were used, we found that vsv replication is independent ...200818677106
brainstem encephalitis associated with chandipura in andhra pradesh outbreak.clinical data of 104 hospitalized children during the 2003 epidemic of encephalitis in andhra pradesh state was retrospectively analysed to know the clinical profile and risk factors associated with mortality. fever was the first symptom associated with altered sensorium, seizures, diarrhoea and vomiting. evolution of illness was very rapid with high fatality (47%). majority of deaths occurred within the first 24 h of illness due to brainstem involvement. on multiple logistic regression analysis ...200817906316
role of intermolecular interactions of vesicular stomatitis virus nucleoprotein in rna encapsidation.the crystal structure of the vesicular stomatitis virus nucleoprotein (n) in complex with rna reveals extensive and specific intermolecular interactions among the n molecules in the 10-member oligomer. what roles these interactions play in encapsidating rna was studied by mutagenesis of the n protein. three n mutants intended for disruption of the intermolecular interactions were designed and coexpressed with the phosphoprotein (p) in an escherichia coli system previously described (t. j. green ...200818003727
attenuation of recombinant vesicular stomatitis virus-human immunodeficiency virus type 1 vaccine vectors by gene translocations and g gene truncation reduces neurovirulence and enhances immunogenicity in mice.recombinant vesicular stomatitis virus (rvsv) has shown great potential as a new viral vector for vaccination. however, the prototypic rvsv vector described previously was found to be insufficiently attenuated for clinical evaluation when assessed for neurovirulence in nonhuman primates. here, we describe the attenuation, neurovirulence, and immunogenicity of rvsv vectors expressing human immunodeficiency virus type 1 gag. these rvsv vectors were attenuated by combinations of the following manip ...200817942549
direct priming of antiviral cd8+ t cells in the peripheral interfollicular region of lymph nodes.it is uncertain how antiviral lymphocytes are activated in draining lymph nodes, the site where adaptive immune responses are initiated. here, using intravital microscopy we show that after infection of mice with vaccinia virus (a large dna virus) or vesicular stomatitis virus (a small rna virus), virions drained to the lymph node and infected cells residing just beneath the subcapsular sinus. naive cd8+ t cells rapidly migrated to infected cells in the peripheral interfollicular region and then ...200818193049
transcription of signal-3 cytokines, il-12 and ifn alpha beta, coincides with the timing of cd8 alpha beta up-regulation during viral infection of common carp (cyprinus carpio l).mammalian naïve cd8+ t cells are activated by antigen (signal 1) and cd28 costimulation (signal 2) to undergo several rounds of cell division, but programming for survival, effector function and memory requires a third signal that can be provided by il-12 and/or type i interferons. functional studies indicate that the route of antigen presentation and costimulation are conserved from fish to mammals. however, the potential of il-12 and ifn alpha beta to act as signal-3 cytokines in infections in ...200818022233
chandipura virus: a major cause of acute encephalitis in children in north telangana, andhra pradesh, india.a hospital-based surveillance was undertaken between may 2005 and april 2006 to elucidate the contribution of chandipura virus (chpv) to acute viral encephalitis cases in children, seroconversion in recovered cases and to compare the seroprevalences of anti-chpv igm and n antibodies in areas reporting cases with those without any case of acute viral encephalitis. during this period, 90 cases of acute encephalitis were hospitalized in the pediatric wards of mahatma gandhi memorial (mgm) hospital, ...200818041027
efficient production of canine interferon-alpha in silkworm bombyx mori by use of a bmnpv/bac-to-bac expression system.we exploited the silkworm bombyx mori for the production of recombinant canine interferon-alpha (caifn-alpha). the recombinant baculovirus harboring canine interferon gene was rapidly generated by the bmnpv/bac-to-bac system that was recently developed. in b. mori-derived cell lines, the expression of the recombinant protein reached maximal levels around 72-96 h post-infection. for the isolation of the expressed recombinant protein from b. mori larvae, the whole bodies of the infected larvae wer ...200818066544
genomic sequence of mandarin fish rhabdovirus with an unusual small non-transcriptional orf.the complete genome of mandarin fish siniperca chuatsi rhabdovirus (scrv) was cloned and sequenced. it comprises 11,545 nucleotides and contains five genes encoding the nucleoprotein n, the phosphoprotein p, the matrix protein m, the glycoprotein g, and the rna-dependent rna polymerase protein l. at the 3' and 5' termini of scrv genome, leader and trailer sequences show inverse complementarity. the n, p, m and g proteins share the highest sequence identities (ranging from 14.8 to 41.5%) with the ...200818068257
20-hete-mediated cytotoxicity and apoptosis in ischemic kidney epithelial cells.20-hete, a metabolite of arachidonic acid, has been implicated as a mediator of free radical formation and tissue death following ischemia-reperfusion (ir) injury in the brain and heart. the present study examined the role of this pathway in a simulated ir renal injury model in vitro. modified self-inactivating lentiviral vectors were generated to stably overexpress murine cyp4a12 following transduction into llc-pk(1) cells (llc-cyp4a12). we compared the survival of control and transduced llc-pk ...200818171997
identification of mavs splicing variants that interfere with rigi/mavs pathway signaling.the mitochondrial anti-viral signaling protein (mavs), also known as cardif, ips-1, kiaa1271 and visa, is a mitochondria associated protein that regulates type i interferon production through coordinated activation of nf-kappab and irf3. the n-terminal card domain of mavs interacts with rigi helicase of upcapped rna detection and the putative traf2 and traf6 binding motifs modulate protein interaction for nf-kappab activation. mavs is encoded by a single gene composed of 6 exons but is generally ...200818207245
akt plays a critical role in replication of nonsegmented negative-stranded rna viruses.the order mononegavirales (comprised of nonsegmented negative-stranded rna viruses or nnsvs) contains many important pathogens. parainfluenza virus 5 (piv5), formerly known as simian virus 5, is a prototypical paramyxovirus and encodes a v protein, which has a cysteine-rich c terminus that is conserved among all paramyxoviruses. the v protein of piv5, like that of many other paramyxoviruses, plays an important role in regulating viral rna synthesis. in this work, we show that v interacts with ak ...200817959676
a conserved motif in region v of the large polymerase proteins of nonsegmented negative-sense rna viruses that is essential for mrna capping.nonsegmented negative-sense (nns) rna viruses cap their mrna by an unconventional mechanism. specifically, 5' monophosphate mrna is transferred to gdp derived from gtp through a reaction that involves a covalent intermediate between the large polymerase protein l and mrna. this polyribonucleotidyltransferase activity contrasts with all other capping reactions, which are catalyzed by an rna triphosphatase and guanylyltransferase. in these reactions, a 5' diphosphate mrna is capped by transfer of ...200818003731
combined vsv oncolytic virus and chemotherapy for squamous cell carcinoma.vesicular stomatitis virus (vsv) is a negative-strand ribonucleic acid (rna) virus that replicates specifically in tumor cells and has oncolytic effects in a variety of malignant tumors. we previously demonstrated recombinant vsv vectors incorporating viral fusion protein (rvsv-f) and interleukin 12 (rvsv-il12) to have significant antitumor effects against squamous cell carcinoma (scc) in a murine model. here we evaluate the potential to combine a potent chemotherapeutic agent for scc (cisplatin ...200818043494
site-specific labeling of enveloped viruses with quantum dots for single virus tracking.this study reports a general method of labeling enveloped viruses with semiconductor quantum dots (qds) for use in single virus trafficking studies. retroviruses, including human immunodeficiency virus (hiv), could be successfully tagged with qds through the membrane incorporation of a short acceptor peptide (ap) that is susceptible to site-specific biotinylation and attachment of streptavidin-conjugated qds. it was found that this ap tag-based qd labeling had little effect on the viral infectiv ...200819079775
development and evaluation of a real-time one step reverse-transcriptase pcr for quantitation of chandipura virus.chandipura virus (chpv), a member of family rhabdoviridae was attributed to an explosive outbreak of acute encephalitis in children in andhra pradesh, india in 2003 and a small outbreak among tribal children from gujarat, western india in 2004. the case-fatality rate ranged from 55-75%. considering the rapid progression of the disease and high mortality, a highly sensitive method for quantifying chpv rna by real-time one step reverse transcriptase pcr (real-time one step rt-pcr) using taqman tec ...200819091082
rhabdovirus matrix protein structures reveal a novel mode of self-association.the matrix (m) proteins of rhabdoviruses are multifunctional proteins essential for virus maturation and budding that also regulate the expression of viral and host proteins. we have solved the structures of m from the vesicular stomatitis virus serotype new jersey (genus: vesiculovirus) and from lagos bat virus (genus: lyssavirus), revealing that both share a common fold despite sharing no identifiable sequence homology. strikingly, in both structures a stretch of residues from the otherwise-di ...200819112510
a recombinant vesicular stomatitis virus replicon vaccine protects chickens from highly pathogenic avian influenza virus (h7n1).highly pathogenic avian influenza viruses (hpaiv) of subtypes h5 and h7 cause fatal disease in poultry (fowl plague) but also have zoonotic potential. currently commercially available vaccines often do not provide sufficient protection and do not allow easy discrimination between vaccinated and infected birds. therefore, vaccination of domestic poultry against h5 and h7 hpaiv is not allowed in many countries, or is only possible after special permission has been provided. we generated a recombin ...200919135116
vesicular stomatitis virus m protein mutant stimulates maturation of toll-like receptor 7 (tlr7)-positive dendritic cells through tlr-dependent and -independent mechanisms.wild-type (wt) vesicular stomatitis virus (vsv) strains stimulate plasmacytoid dendritic cells (pdc) through toll-like receptor 7 (tlr7) and its adaptor molecule, myd88. granulocyte-macrophage colony-stimulating factor-derived dc (g-dc), which do not express tlr7, are unresponsive to wt vsv due to inhibition of cellular gene expression by the matrix (m) protein. in contrast to its recombinant wt (rwt) counterpart, an m protein mutant of vsv, rm51r-m virus, stimulates maturation of g-dc independe ...200919144711
induction of apobec3 in vivo causes increased restriction of retrovirus infection.apobec3 proteins are important cellular factors that restrict infection by a number of viruses, including human immunodeficiency virus type 1 (hiv-1). previously, we found that the mouse apobec3 (ma3) restricts infection by mouse mammary tumor virus (mmtv) in its natural host. dendritic cells (dcs) are the first in vivo targets of mmtv infection. in this study, we demonstrate that ma3 expressed in target cells restricts mmtv infection in dcs ex vivo and in vivo. by comparing infection of dcs fro ...200919153238
[comparison of characteristics of svcv strains isolated in china and in europe].in the nationwide epidemiological investigation, svcv-741 was for the first time isolated in beijing region, china in 2003, and designated as svcv asian strain. in this paper, we compared svcv-741 (asian strains isolated in china) with svcv-10/3 (europe reference strain) on their physico-chemical, biological and morphological characteristics. the results indicated that there were no distinct differences between two svcv strains on phycico-chemical and morphological characteristics. the main exis ...200919437886
in situ (in vivo) gene transfer into murine bone marrow stem cells.adult bone marrow stem cell is an ideal target for gene therapy of genetic diseases, selected malignant diseases, and aids. the in vivo approach of lentivirus vector (lv)-mediated stem cell gene transfer by intrafemoral (if) injection can take full advantage of any source of stem cells residing in the bone cavity. such an approach may avoid several difficulties encountered by ex vivo hematopoietic stem cell (hsc) gene transfer. we have shown that both hsc and mesenchymal stem/progenitor cells (m ...200919110626
vesicular stomatitis virus matrix protein mutations that affect association with host membranes and viral nucleocapsids.viral matrix (m) proteins bind the nucleoprotein core (nucleocapsid) to host membranes during the process of virus assembly by budding. previous studies using truncated m proteins had implicated the n-terminal 50 amino acids of the vesicular stomatitis virus m protein in binding both membranes and nucleocapsids and a sequence from amino acids 75-106 as an additional membrane binding region. structure-based mutations were introduced into these two regions, and their effects on membrane associatio ...200919088071
prime-boost vaccination with recombinant mumps virus and recombinant vesicular stomatitis virus vectors elicits an enhanced human immunodeficiency virus type 1 gag-specific cellular immune response in rhesus macaques.intramuscular inoculation of rhesus macaques with one or more doses of recombinant vesicular stomatitis virus (rvsv) expressing human immunodeficiency virus type 1 (hiv-1) gag (rvsvgag) typically elicits peak cellular immune responses of 500 to 1,000 gamma interferon (ifn-gamma) enzyme-linked immunospots (elispots)/10(6) peripheral blood lymphocytes (pbl). here, we describe the generation of a novel recombinant mumps virus (rmuv) expressing hiv-1 gag (rmuvgag) and measure the gag-specific cellul ...200919625392
rho gtpases modulate entry of ebola virus and vesicular stomatitis virus pseudotyped vectors.to explore mechanisms of entry for ebola virus (ebov) glycoprotein (gp) pseudotyped virions, we used comparative gene analysis to identify genes whose expression correlated with viral transduction. candidate genes were identified by using ebov gp pseudotyped virions to transduce human tumor cell lines that had previously been characterized by cdna microarray. transduction profiles for each of these cell lines were generated, and a significant positive correlation was observed between rhoc expres ...200919625394
ars2 regulates both mirna- and sirna- dependent silencing and suppresses rna virus infection in drosophila.intrinsic immune responses autonomously inhibit viral replication and spread. one pathway that restricts viral infection in plants and insects is rna interference (rnai), which targets and degrades viral rna to limit infection. to identify additional genes involved in intrinsic antiviral immunity, we screened drosophila cells for modulators of viral infection using an rnai library. we identified ars2 as a key component of drosophila antiviral immunity. loss of ars2 in cells, or in flies, increas ...200919632183
dna vaccines expressing retrovirus-like particles are efficient immunogens to induce neutralizing antibodies.we aimed at improving dna vaccination efficiency for inducing neutralizing antibodies. we used plasmids encoding gag of mlv and envelope proteins of vsv or wnv. upon in vivo injection, they generate retrovirus-derived vlps pseudotyped with these envelopes expressed in their wild-type conformation. we show that these plasmo-retrovlps induce potent humoral responses, the efficacy of which could be improved by co-administration of dna encoding adjuvant cytokines. antibodies against vsv or wnv were ...200919656495
antiviral screening of forty-two egyptian medicinal plants.egyptian medicinal plants are well known by their diverse uses in traditional folk medicine to cure various ailments including infectious diseases. forty-two egyptian medicinal plant species were selected from local market and were subjected to antiviral screening bioassay to investigate and to evaluate their biological activities.200919666102
mechanical transmission of vesicular stomatitis new jersey virus by simulium vittatum (diptera: simuliidae) to domestic swine (sus scrofa).biting flies have been suggested as mechanical vectors of vesicular stomatitis new jersey virus (family rhabdoviridae, genus vesiculovirus, vsnjv) in livestock populations during epidemic outbreaks in the western united states. we conducted a proof-of-concept study to determine whether biting flies could mechanically transmit vsnjv to livestock by using a black fly, simulium vittatum zetterstedt (diptera: simuliidae), domestic swine, sus scrofa l., model. black flies mechanically transmitted vsn ...200919960709
mutations in the c-terminal loop of the nucleocapsid protein affect vesicular stomatitis virus rna replication and transcription differentially.the 2.9-a structure of the vesicular stomatitis virus nucleocapsid (n) protein bound to rna shows the rna to be tightly sequestered between the two lobes of the n protein. domain movement of the lobes of the n protein has been postulated to facilitate polymerase access to the rna template. we investigated the roles of individual amino acid residues in the c-terminal loop, involved in long-range interactions between n protein monomers, in forming functional ribonucleoprotein (rnp) templates. the ...200919726519
vesicular stomatitis virus inhibits mitotic progression and triggers cell death.vesicular stomatitis virus (vsv) infects and kills a wide range of cell types; however, the mechanisms involved in vsv-mediated cell death are not fully understood. here we show that vsv infection interferes with mitotic progression, resulting in cell death. this effect requires the interaction of vsv matrix (m) protein with the rae1-nup98 complex in mitosis, which is associated with a subset of ribonucleoproteins (rnps). vsv displaced rae1 from spindle poles, caused spindle abnormalities and tr ...200919745842
recombinant vectors as influenza vaccines.the antiquated system used to manufacture the currently licensed inactivated influenza virus vaccines would not be adequate during an influenza virus pandemic. there is currently a search for vaccines that can be developed faster and provide superior, long-lasting immunity to influenza virus as well as other highly pathogenic viruses and bacteria. recombinant vectors provide a safe and effective method to elicit a strong immune response to a foreign protein or epitope. this review explores the a ...200919768410
expression of ifn-beta enhances both efficacy and safety of oncolytic vesicular stomatitis virus for therapy of mesothelioma.our preclinical and clinical trials using a replication-defective adenoviral vector expressing ifn-beta have shown promising results for the treatment of malignant mesothelioma. based on the hypotheses that a replication-competent vesicular stomatitis virus (vsv) oncolytic vector would transduce more tumor cells in vivo, that coexpression of the immunostimulatory ifn-beta gene would enhance the immune-based effector mechanisms associated both with regression of mesotheliomas and with vsv-mediate ...200919773437
glycoprotein-dependent acidification of vesicular stomatitis virus enhances release of matrix protein.to study vesicular stomatitis virus (vsv) entry and uncoating, we generated a recombinant vsv encoding a matrix (m) protein containing a c-terminal tetracysteine lumio tag (rvsv-ml) that could be fluorescently labeled using biarsenical compounds. quantitative confocal microscopy showed that there is a transient loss of fluorescence at early times after the initiation of endocytosis of rvsv-ml-green (rvsv-mlg) virions, which did not occur when cells were treated with bafilomycin a1. the reduction ...200919776119
insertion of enhanced green fluorescent protein in a hinge region of vesicular stomatitis virus l polymerase protein creates a temperature-sensitive virus that displays no virion-associated polymerase activity in vitro.the rna-dependent rna polymerase of viruses belonging to the order mononegavirales is part of a large multifunctional l protein that also catalyzes viral mrna capping and cap methylation. the l protein of this diverse group of agents displays six blocks of conserved sequences. the precise relationship between these conserved regions and individual functions is largely unknown, except for "domain" vi that clearly encodes a viral mrna cap methylase. the l protein of morbilliviruses (family paramyx ...200919793815
pcbp2 mediates degradation of the adaptor mavs via the hect ubiquitin ligase aip4.mavs is critical in innate antiviral immunity as the sole adaptor for rig-i-like helicases. mavs regulation is essential for the prevention of excessive harmful immune responses. here we identify pcbp2 as a negative regulator in mavs-mediated signaling. overexpression of pcbp2 abrogated cellular responses to viral infection, whereas knockdown of pcbp2 exerted the opposite effect. pcbp2 was induced after viral infection, and its interaction with mavs led to proteasomal degradation of mavs. pcbp2 ...200919881509
a single peptide-mhc complex positively selects a diverse and specific cd8 t cell repertoire.pathogen recognition by t cells is dependent on their exquisite specificity for self-major histocompatibility complex (mhc) molecules presenting a bound peptide. although this specificity results from positive and negative selection of developing t cells in the thymus, the relative contribution of these two processes remains controversial. to address the relation between the selecting peptide-mhc complex and the specificity of mature t cells, we generated transgenic mice that express a single pe ...200919892989
viral strategies for studying the brain, including a replication-restricted self-amplifying delta-g vesicular stomatis virus that rapidly expresses transgenes in brain and can generate a multicolor golgi-like expression.viruses have substantial value as vehicles for transporting transgenes into neurons. each virus has its own set of attributes for addressing neuroscience-related questions. here we review some of the advantages and limitations of herpes, pseudorabies, rabies, adeno-associated, lentivirus, and others to study the brain. we then explore a novel recombinant vesicular stomatitis virus (dg-vsv) with the g-gene deleted and transgenes engineered into the first position of the rna genome, which replicat ...200919672982
a genetic background with low mutational robustness is associated with increased adaptability to a novel host in an rna virus.although mutational robustness is central to many evolutionary processes, its relationship to evolvability remains poorly understood and has been very rarely tested experimentally. here, we measure the evolvability of vesicular stomatitis virus in two genetic backgrounds with different levels of mutational robustness. we passaged the viruses into a novel cell type to model a host-jump episode, quantified changes in infectivity and fitness in the new host, evaluated the cost of adaptation in the ...200919702844
ribose 2'-o methylation of the vesicular stomatitis virus mrna cap precedes and facilitates subsequent guanine-n-7 methylation by the large polymerase protein.during conventional mrna cap formation, two separate methyltransferases sequentially modify the cap structure, first at the guanine-n-7 (g-n-7) position and subsequently at the ribose 2'-o position. for vesicular stomatitis virus (vsv), a prototype of the nonsegmented negative-strand rna viruses, the two methylase activities share a binding site for the methyl donor s-adenosyl-l-methionine and are inhibited by individual amino acid substitutions within the c-terminal domain of the large (l) poly ...200919710136
vsv infection is sensed by drosophila, attenuates nutrient signaling, and thereby activates antiviral autophagy.innate immune mechanisms are the first line of defense against pathogens including viruses. this work identifies autophagy, an innate intracellular degradative pathway, as antiviral against vesicular stomatitis virus (vsv) in drosophila. vsv is sensed by cells via the surface glycoprotein leading to the attenuation of the nutrient signaling pathway thereby activating an antiviral autophagic program.200919713743
specific intracellular localization and antiviral property of genetic and splicing variants in bovine mx1.in bovine mx1, only an amino acid substitution between ile and met at position 120 was detected by the nucleotide sequence and mismatched pcr-rflp technique. the ile variant was assumed to distribute mainly in the bovine population since the gene frequency was 79.3%. furthermore, we cloned water buffalo mx1 cdna, which showed 51 nucleotide and 20 amino acid substitutions in comparison with that of the cow. another kind of mx1 cdna, bovine mx1b cdna, was found and it was deduced to cause 27 amino ...200919951175
in vitro antiviral activity of dehydroepiandrosterone and its synthetic derivatives against vesicular stomatitis virus.in this work the antiviral activity of 20 dehydroepiandrosterone (dhea) analogs with different substituents at positions c-3, c-15, c-16 and c-17 were evaluated against vesicular stomatitis virus (vsv) in vero cell cultures. the selectivity indexes (si) obtained with dhea and epiandrosterone (ea) were 50 and 72.6, respectively. the work showed that the compounds 21-norpregna-5,17(20)-dien-3beta,16alpha-diyl-diacetate, 17,17-ethylendioxyandrostan-5,15-dien-3beta-ol and 3beta-hydroxypregn-17(20)-e ...200918682333
hnrnps relocalize to the cytoplasm following infection with vesicular stomatitis virus.vesicular stomatitis virus (vsv) matrix protein inhibits nuclear-cytoplasmic mrna transport. the goal of this work is to determine whether vsv inhibits the nuclear-cytoplasmic transport of heterogeneous ribonucleoproteins (hnrnps), which are thought to serve as mrna export factors. confocal microscopy experiments showed that hnrnpa1, hnrnpk, and hnrnpc1/c2, but not hnrnpb1 or lamin a/c, are relocalized to the cytoplasm during vsv infection. we determined whether protein import is inhibited by vs ...200919004954
recombinant vesicular stomatitis virus targeted to her2/neu combined with anti-ctla4 antibody eliminates implanted mammary tumors.vesicular stomatitis virus (vsv) is being developed for cancer therapy. we created a recombinant replicating vsv (rrvsv) that preferentially infected her2/neu expressing breast cancer cells. we now used this rrvsv to treat macroscopic peritoneal tumor implants of a mouse mammary tumor cell line stably transfected to express her2/neu. rrvsv therapy alone prolonged survival but did not cure any animals. rrvsv therapy combined with antibody to tgfb or antibody to il-10 receptor (il-10r) each produc ...200918654610
structure-activity relationships for dipeptide prodrugs of acyclovir: implications for prodrug design.a series of water-soluble dipeptide ester prodrugs of the antiviral acyclovir (acv) were evaluated for their chemical stability, cytotoxicity, and antiviral activity against several strains of herpes simplex-1 and -2, vaccinia, vesicular stomatitis, cytomegalovirus and varicella zoster viruses. acv dipeptide esters were very active against herpetic viruses, independently of the rate at which they liberate the parent drug. their minimum cytotoxic concentrations were above 100 microm and the resul ...200918848738
immunization with single-cycle siv significantly reduces viral loads after an intravenous challenge with siv(mac)239.strains of simian immunodeficiency virus (siv) that are limited to a single cycle of infection were evaluated for the ability to elicit protective immunity against wild-type siv(mac)239 infection of rhesus macaques by two different vaccine regimens. six animals were inoculated at 8-week intervals with 6 identical doses consisting of a mixture of three different envelope variants of single-cycle siv (scsiv). six additional animals were primed with a mixture of cytoplasmic domain-truncated envelop ...200919165322
kernel energy method applied to vesicular stomatitis virus nucleoprotein.the kernel energy method (kem) is applied to the vesicular stomatitis virus (vsv) nucleoprotein (pdb id code 2qvj). the calculations employ atomic coordinates from the crystal structure at 2.8-a resolution, except for the hydrogen atoms, whose positions were modeled by using the computer program hyperchem. the calculated kem ab initio limited basis hartree-fock energy for the full 33,175 atom molecule (including hydrogen atoms) is obtained. in the kem, a full biological molecule is represented b ...200919188588
computational fitness landscape for all gene-order permutations of an rna virus.how does the growth of a virus depend on the linear arrangement of genes in its genome? answering this question may enhance our basic understanding of virus evolution and advance applications of viruses as live attenuated vaccines, gene-therapy vectors, or anti-tumor therapeutics. we used a mathematical model for vesicular stomatitis virus (vsv), a prototype rna virus that encodes five genes (n-p-m-g-l), to simulate the intracellular growth of all 120 possible gene-order variants. simulated yiel ...200919197345
local type i ifn receptor signaling protects against virus spread within the central nervous system.several neurotropic viruses such as vesicular stomatitis virus (vsv) induce peripheral neutralizing ab responses and still can infect cells within the cns. to address whether local type i ifn receptor (ifnar) triggering plays a role in controlling virus replication within the brain, we generated mice with a cell type-specific ifnar deletion in neuroectodermal cells of the cns (nescre(+/-)ifnar(flox/flox)). intranasal vsv infection with 10(3) pfu was well tolerated by wild-type mice, whereas conv ...200919201884
recombinant vesicular stomatitis virus expressing influenza nucleoprotein induces cd8 t-cell responses that enhance antibody-mediated protection after lethal challenge with influenza virus.live attenuated vaccine vectors based on recombinant vesicular stomatitis viruses (rvsvs) expressing foreign antigens are highly effective vaccines in animal models. in this study, we report that an rvsv expressing influenza nucleoprotein (vsv np) from the first position of the vsv genome induces robust anti-np cd8 t cells in immunized mice. these cd8 t cells are phenotypically similar to those induced by natural influenza infection and are cytotoxic in vivo. animals immunized with an rvsv expre ...200919244472
preparation and biological evaluation of a glycosylated fusion interferon directed to hepatic receptors.the antiviral activity and biodistribution of a glycosylated fusion interferon directed to hepatic receptors were evaluated to determine whether its pharmaceutical concentration in the liver could be improved. the novel glycosylated fusion interferon, galactosyl-human serum albumin-interferon-alpha2b (g-hsa-ifn) was obtained from a long-term recombinant fusion protein (hsa-ifn) by covalent coupling with a bifunctional reagent, 2-imino-2-ethyloxymethy1-1-thiogalactose. there are about 24 thiogala ...200919252292
peripheral dendritic cells are essential for both the innate and adaptive antiviral immune responses in the central nervous system.intranasal application of vesicular stomatitis virus (vsv) causes acute infection of the central nervous system (cns). however, vsv encephalitis is not invariably fatal, suggesting that the cns may contain a professional antigen-presenting cell (apc) capable of inducing or propagating a protective antiviral immune response. to examine this possibility, we first characterized the cellular elements that infiltrate the brain as well as the activation status of resident microglia in the brains of no ...200919264338
comparison of vesicular stomatitis virus pseudotyped with the s proteins from a porcine and a human coronavirus.the surface proteins s of severe acute respiratory syndrome coronavirus (sars-cov) and transmissible gastroenteritis virus (tgev) were compared for their ability to mediate infection of viral pseudotypes based on vesicular stomatitis virus (vsv). the cell tropism of the respective pseudotypes corresponded to the tropism of the viruses from which the s protein was derived. higher infectivity values were obtained with the sars-cov s protein than with the tgev s protein. differences were observed w ...200919264610
new insights into the evolution of ifns: zebrafish group ii ifns induce a rapid and transient expression of ifn-dependent genes and display powerful antiviral activities.the ifns and their receptors have existed in early chordates for approximately 500 million years and represent the early elements in innate and adaptive immunity. both types i and ii ifns have been discovered in fish, and type i has recently been classified into two groups based on their primary protein sequences. however, the biological activities of fish ifns and their roles in infection are largely unknown. using the zebrafish and manageable bacterial (streptococcus iniae) and viral (spring v ...200919265122
infection of melanoplus sanguinipes grasshoppers following ingestion of rangeland plant species harboring vesicular stomatitis virus.knowledge of the many mechanisms of vesicular stomatitis virus (vsv) transmission is critical for understanding of the epidemiology of sporadic disease outbreaks in the western united states. migratory grasshoppers [melanoplus sanguinipes (fabricius)] have been implicated as reservoirs and mechanical vectors of vsv. the grasshopper-cattle-grasshopper transmission cycle is based on the assumptions that (i) virus shed from clinically infected animals would contaminate pasture plants and remain inf ...200919286779
lipid rafts play an important role in the vesicular stomatitis virus life cycle.lipid rafts are involved in the life cycle of many viruses. in this study, we investigated the role of lipids in the life cycle of vesicular stomatitis virus (vsv). cholesterol depletion by pretreatment of bhk cells or vsv particles with methyl-beta-cyclodextrin (mbetacd), a cholesterol-sequestering drug, inhibited the production of vsv dramatically. this effect was reversible, and virus production was restored by the addition of cholesterol, indicating that the reduction was caused by the loss ...200919288237
single-amino-acid alterations in a highly conserved central region of vesicular stomatitis virus n protein differentially affect the viral nucleocapsid template functions.the nucleocapsid protein (n) of vesicular stomatitis virus and other rhabdoviruses plays a central role in the assembly and template functions of the viral n-rna complex. the crystal structure of the viral n-rna complex suggests that the central region of the n protein interacts with the viral rna. sequence alignment of rhabdovirus n proteins revealed several highly conserved regions, one of which spanned residues 282 to 291 (glsskspyss) in the central region of the molecule. alanine-scanning mu ...200919321605
the cd8+ memory t-cell state of readiness is actively maintained and reversible.the ability of the adaptive immune system to respond rapidly and robustly upon repeated antigen exposure is known as immunologic memory, and it is thought that acquisition of memory t-cell function is an irreversible differentiation event. in this study, we report that many phenotypic and functional characteristics of antigen-specific cd8 memory t cells are lost when they are deprived of contact with dendritic cells. under these circumstances, memory t cells reverted from g(1) to the g(0) cell-c ...200919617575
autophagy is an essential component of drosophila immunity against vesicular stomatitis virus.intrinsic innate immune mechanisms are the first line of defense against pathogens and exist to control infection autonomously in infected cells. here, we showed that autophagy, an intrinsic mechanism that can degrade cytoplasmic components, played a direct antiviral role against the mammalian viral pathogen vesicular stomatitis virus (vsv) in the model organism drosophila. we found that the surface glycoprotein, vsv-g, was likely the pathogen-associated molecular pattern (pamp) that initiated t ...200919362021
vesicular stomatitis virus enters cells through vesicles incompletely coated with clathrin that depend upon actin for internalization.many viruses that enter cells by clathrin-dependent endocytosis are significantly larger than the dimensions of a typical clathrin-coated vesicle. the mechanisms by which viruses co-opt the clathrin machinery for efficient internalization remain uncertain. here we examined how clathrin-coated vesicles accommodate vesicular stomatitis virus (vsv) during its entry into cells. using high-resolution imaging of the internalization of single viral particles into cells expressing fluorescent clathrin a ...200919390604
a temperature sensitive vsv identifies l protein residues that affect transcription but not replication.to investigate the polymerase components selectively involved in transcription versus replication of vesicular stomatitis virus (vsv), we sequenced the polymerase gene of a conditionally rna defective, temperature sensitive vsv: ts(g)114, which has a phenotype upon shift from permissive to non-permissive temperature of shut-down of mrna transcription and unaffected genome replication. sequence analysis of the ts(g)114 l gene identified three altered amino acid residues in the l protein. these th ...200919395055
recombinant glycoprotein based vaccine for chandipura virus infection.chandipura virus (chpv) has emerged as an important pediatric encephalitis-causing pathogen with very high mortality in india. no specific vaccine or treatment is available till date. we attempted to prepare a candidate vaccine employing recombinant chpv glycoprotein (rgp). the glycoprotein gene (g-gene) of chpv was expressed using baculovirus expression system. the rgp was purified by hplc and used for mice immunization, 3 doses, and 4 weeks apart. one microgram rgp was found to be optimum. ser ...200919428894
in vivo biodistribution of a highly attenuated recombinant vesicular stomatitis virus expressing hiv-1 gag following intramuscular, intranasal, or intravenous inoculation.recombinant vesicular stomatitis viruses (rvsvs) are being developed as potential hiv-1 vaccine candidates. to characterize the in vivo replication and dissemination of rvsv vectors in mice, high doses of a highly attenuated vector expressing hiv-1 gag, rvsv(in)-n4ct9-gag1, and a prototypic reference virus, rvsv(in)-hivgag5, were delivered intramuscularly (im), intranasally (in), or intravenously (iv). we used quantitative, real-time rt-pcr (q-pcr) and standard plaque assays to measure the tempo ...200919428903
highly sensitive fetal goat tongue cell line for detection and isolation of foot-and-mouth disease virus.a fetal goat cell line (zz-r 127) supplied by the collection of cell lines in veterinary medicine of the friedrich loeffler institute was examined for susceptibility to infection by foot-and-mouth disease (fmd) virus (fmdv) and by two other viruses causing clinically indistinguishable vesicular conditions, namely, the viruses of swine vesicular disease and vesicular stomatitis. primary bovine thyroid (bty) cells are generally the most sensitive cell culture system for fmdv detection but are prob ...200919656987
a neutralization test for specific detection of nipah virus antibodies using pseudotyped vesicular stomatitis virus expressing green fluorescent protein.nipah virus (niv) is a new zoonotic paramyxovirus that emerged in 1998 and is now classified in the genus henipavirus along with the closely related hendra virus (hev). niv is highly pathogenic in several vertebrate species including humans, and the lack of available vaccines or specific treatment restricts it to biosafety level 4 (bsl4) containment. a serum neutralization test was developed for measuring niv neutralizing antibodies under bsl2 conditions using a recombinant vesicular stomatitis ...200919433112
viruses and endosome membrane dynamics.cell surface molecules, ligands, and solutes can be endocytosed into animal cells via several pathways in addition to clathrin-mediated endocytosis, which all seem to lead to canonical endosomes. it seems that viruses can enter and infect cells through most of, if not all, endocytic routes, having evolved different, sometimes elaborate, strategies to (mis)use cellular machineries to their own benefit during infection. in this short review, i will discuss recent progress in understanding the path ...200919443190
a pseudotype baculovirus-mediated vaccine confers protective immunity against lethal challenge with h5n1 avian influenza virus in mice and chickens.baculovirus has emerged recently as a novel and attractive gene delivery vehicle for mammalian cells. in this study, baculovirus pseudotyped with vesicular stomatitis virus glycoprotein was used as a vector to express the hemagglutinin (ha) protein of highly pathogenic h5n1 avian influenza virus, a/chicken/hubei/327/2004 (hb/327). the resultant recombinant baculovirus (bv-g-ha) mediated gene delivery and ha expression efficiently in mammalian cells. mice immunized with 1 x 10(9)pfu of bv-g-ha de ...200919446339
late generation lentiviral vectors: evaluation of inflammatory potential in human airway epithelial cells.lentiviruses (lvs) are considered one of the most promising tools for gene transfer, however, their potential to induce pro-inflammatory cytokines on delivery into the respiratory tissue remains to be established. here we tested a third-generation vesicular stomatitis virus (vsv)-g pseudotyped lv vector in the two respiratory epithelial cell lines a549 and cft1-c2. we observed that the vsv-g lv vector does not induce (a) activation of the nuclear factor (nf)-kappab, which intervenes in transcrip ...200919447514
stochastic kinetic modeling of vesicular stomatitis virus intracellular growth.by building kinetic models of biological networks one may advance the development of new modeling approaches while gaining insights into the biology. we focus here on building a stochastic kinetic model for the intracellular growth of vesicular stomatitis virus (vsv), a well-studied virus that encodes five genes. the essential network of vsv reactions creates challenges to stochastic simulation owing to (i) delayed reactions associated with transcription and genome replication, (ii) production o ...200919459014
the lipidomes of vesicular stomatitis virus, semliki forest virus, and the host plasma membrane analyzed by quantitative shotgun mass spectrometry.although enveloped virus assembly in the host cell is a crucial step in the virus life cycle, it remains poorly understood. one issue is how viruses include lipids in their membranes during budding from infected host cells. to analyze this issue, we took advantage of the fact that baby hamster kidney cells can be infected by two different viruses, namely, vesicular stomatitis virus and semliki forest virus, from the rhabdoviridae and togaviridae families, respectively. we purified the host plasm ...200919474104
the e3 ubiquitin ligase nrdp1 'preferentially' promotes tlr-mediated production of type i interferon.e3 ubiquitin ligases are important in both innate and adaptive immunity. here we report that nrdp1, an e3 ubiquitin ligase, inhibited the production of proinflammatory cytokines but increased interferon-beta production in toll-like receptor-triggered macrophages by suppressing adaptor myd88-dependent activation of transcription factors nf-kappab and ap-1 while promoting activation of the kinase tbk1 and transcription factor irf3. nrdp1 directly bound and polyubiquitinated myd88 and tbk1, which l ...200919483718
inhibition of lassa virus glycoprotein cleavage and multicycle replication by site 1 protease-adapted alpha(1)-antitrypsin variants.proteolytic processing of the lassa virus envelope glycoprotein precursor gp-c by the host proprotein convertase site 1 protease (s1p) is a prerequisite for the incorporation of the subunits gp-1 and gp-2 into viral particles and, hence, essential for infectivity and virus spread. therefore, we tested in this study the concept of using s1p as a target to block efficient virus replication.200919488405
akt inhibitor akt-iv blocks virus replication through an akt-independent mechanism.many viruses activate the phosphatidylinositol 3'-kinase (pi3k)/akt intracellular signaling pathway to promote viral replication. we have analyzed whether a rapidly replicating rhabdovirus, vesicular stomatitis virus (vsv), requires the pi3k/akt signaling pathway for its replication. through the use of chemical inhibitors of pi3k and akt, we show that vsv replication and cytopathic effects do not require activation of these kinases. inhibitors that block the activating phosphorylations of akt at ...200919740993
bioinformatics comparison of g protein of isfahan virus with the same proteins of two other closely related viruses of the genus vesiculovirus.since there are not much experimental data available about different structural properties of isfahan virus (isfv), in the present investigation, computational study of g protein of isfv was performed and the results were compared with g proteins of chandipura virus (chpv) and piry virus (pv). calculation of amino acid compositions of g proteins of viruses was done by pseaac server. predictions of localization, sequence of signal peptides, c, n and o glycosylation sites, transmembrane helices, c ...200919508221
thermosensitivity of the reverse transcription process as an inactivation mechanism of lentiviral vectors.lentiviral vectors are an important tool for gene transfer research and gene therapy purposes. however, the low stability of these vectors affects their production, storage, and efficacy in preclinical and clinical settings. in the present work the mechanism underlying the thermosensitivity of lentiviral vectors was evaluated. for lentiviral vectors pseudotyped with amphotropic and rdpro envelopes, the capacity to perform reverse transcription was lost rapidly at 37 degrees c, in high correlatio ...200919537947
secretory expression of porcine interferon-gamma in baculovirus using hbm signal peptide and its inhibition activity on the replication of porcine reproductive and respiratory syndrome virus.the gene sequence encoding mature porcine interferon-gamma (poifn-gamma) fused with a c-terminal 6x histidine tag was cloned into the baculovirus pfastbac dual vector of the bac-to-bac baculovirus expression system under the control of ph promoter. the authentic signal sequence of porcine interferon-gamma was substituted with the honeybee melittin (hbm) signal sequence, and expressed in insect cells. the recombinant proteins were detected by sds-page and immunofluorescence assay. the nickel affi ...200919556014
development of a neutralization assay for nipah virus using pseudotype particles.nipah virus (niv) and hendra virus (hev) are zoonotic paramyxoviruses capable of causing severe disease in humans and animals. these viruses require biosafety level 4 (bsl-4) containment. like other paramyxoviruses, the plaque reduction neutralization test (prnt) can be used to detect antibodies to the surface glycoproteins, fusion (f) and attachment (g), and prnt titers give an indication of protective immunity. unfortunately, for niv and hev, the prnt must be performed in bsl-4 containment and ...200919559943
toll-like receptor signaling controls reactivation of kshv from latency.kaposi's sarcoma-associated herpesvirus (kshv) is the etiological agent of kaposi's sarcoma, primary effusion lymphoma (pel), and multicentric castleman's disease. like other herpesviruses, kshv establishes life-long latency in the human host with intermittent periods of reactivation. physiological triggers of herpesviral reactivation are poorly defined. toll-like receptors (tlrs) recognize pathogens and are vital for the host innate immune response. we screened multiple tlr agonists for their a ...200919564611
vesicular stomatitis virus induces apoptosis primarily through bak rather than bax by inactivating mcl-1 and bcl-xl.vesicular stomatitis virus (vsv) induces apoptosis via the mitochondrial pathway. the mitochondrial pathway is regulated by the bcl-2 family of proteins, which consists of both pro- and antiapoptotic members. to determine the relative importance of the multidomain proapoptotic bcl-2 family members bak and bax, hela cells were transfected with bak and/or bax small interfering rna (sirna) and subsequently infected with recombinant wild-type vsv. our results showed that bak is more important than b ...200919587033
analysis of virion associated host proteins in vesicular stomatitis virus using a proteomics approach.vesicular stomatitis virus (vsv) is the prototypic rhabdovirus and the best studied member of the order mononegavirales. there is now compelling evidence that enveloped virions released from infected cells carry numerous host (cellular) proteins some of which may play an important role in viral replication. although several cellular proteins have been previously shown to be incorporated into vsv virions, no systematic study has been done to reveal the host protein composition for virions of vsv ...200919821998
[oncolytic virus therapy using vesicular stomatitis virus]. 200919847736
[transcriptional profiles of intestinal pig epithelial cell jejenum 2 cultures infected by vesicular stomatitis virus].to better understand the host inflammatory responses, in particular inflammatory cytokines responses of vesicular stomatitis virus (vsv) infection, and the host-vsv interaction.200919873763
phylogenetic analysis of spring viraemia of carp virus isolates from austria indicates the existence of at least two subgroups within genogroup id.genetic relationships between 22 spring viraemia of carp virus (svcv) isolates from austria collected between 1994 and 2007 were determined based on the partial nucleotide sequence of the glycoprotein gene (g gene). phylogenetic analyses located all austrian isolates except one in genogroup id. one isolate collected in 2007 was placed within the svcv ia genogroup. more importantly, the study also revealed 3 distinct clusters within genogroup id, designated id1, id2 and id3. existence of subgroup ...200919593931
microrna-146a feedback inhibits rig-i-dependent type i ifn production in macrophages by targeting traf6, irak1, and irak2.upon recognition of viral components by pattern recognition receptors, including tlrs and retinoic acid-inducible gene i (rig-i)- like helicases, cells are activated to produce type i ifn and proinflammatory cytokines. these pathways are tightly regulated by host to prevent inappropriate cellular response, but viruses can down-regulate these pathways for their survival. recently, identification of negative regulators for cytoplasmic rna-mediated antiviral signaling, especially the rig-i pathway, ...200919596990
vesicular stomatitis virus as a novel cancer vaccine vector to prime antitumor immunity amenable to rapid boosting with adenovirus.vesicular stomatitis virus (vsv) has proven to be an effective vaccine vector for immunization against viral infection, but its potential to induce an immune response to a self-tumor antigen has not been investigated. we constructed a recombinant vsv expressing human dopachrome tautomerase (hdct) and evaluated its immunogenicity in a murine melanoma model. intranasal delivery of vsv-hdct activated both cd4(+) and cd8(+) dct-specific t-cell responses. the magnitude of these responses could be sig ...200919603003
characterization of the complete genome sequence of pike fry rhabdovirus.the complete genome sequence of pike fry rhabdovirus (pfrv), consisting of 11,097 nucleotides, was determined. the genome contains five genes, encoding the nucleoprotein (n), phosphoprotein (p), matrix protein (m), glycoprotein (g), and rna-dependent rna polymerase (l) protein in the order 3'-n-p-m-g-l-5'. 3' leader- and 5' trailer-sequences in the pfrv genome show inverse complementarity. the pfrv proteins share the highest homology to the proteins of spring viremia of carp virus (svcv), rangin ...200919603256
enhanced oncolytic potency of vesicular stomatitis virus through vector-mediated inhibition of nk and nkt cells.recombinant oncolytic viruses represent a promising alternative option for the treatment of malignant cancers. we have reported earlier the safety and efficacy of recombinant vesicular stomatitis virus (vsv) vectors in a rat model of hepatocellular carcinoma (hcc). however, the full potential of vsv therapy is limited by a sudden decline in intratumoral virus replication observed early after viral administration, a phenomenon that coincides with an accumulation of inflammatory cells within infec ...200918846115
long-term vaccine protection from aids and clearance of viral dna following shiv89.6p challenge.in an earlier study, our group vaccinated rhesus macaques with vesicular stomatitis virus (vsv) vectors expressing gag, pol, and env proteins from a hybrid simian/human immunodeficiency virus (shiv). this was followed by a single boost with modified vaccinia virus ankara (mva) vectors expressing the same proteins. following challenge with shiv89.6p, vaccinated animals cleared challenge virus rna from the blood by day 150 and maintained normal cd4 t cell counts for 8 months. here we report on the ...200919135115
lower levels of gamma interferon expressed by a pseudotyped single-cycle simian immunodeficiency virus enhance immunogenicity in rats.a vaccine for human immunodeficiency virus (hiv) infection is desperately needed to control the aids pandemic. to address this problem, we constructed single-cycle simian immunodeficiency viruses (sivs) pseudotyped with the glycoprotein of vesicular stomatitis virus and expressing different levels of gamma interferon (ifn-gamma) as a potential vaccine strategy. we previously showed that ifn-gamma expression by pseudotyped sivs does not alter viral single-cycle infectivity. t cells primed with de ...200919073726
recombinant vesicular stomatitis virus-based west nile vaccine elicits strong humoral and cellular immune responses and protects mice against lethal challenge with the virulent west nile virus strain lsu-ar01.vesicular stomatitis virus (vsv) has been extensively utilized as a viral vector system for the induction of protective immune responses against a variety of pathogens. we constructed recombinant vsvs specifying either the indiana or chandipura virus g glycoprotein and expressing the west nile virus (wnv) envelope (e) glycoprotein. mice were intranasally vaccinated using a prime (indiana)-boost (chandipura) immunization approach and challenged with the virulent wnv-lsu-ar01. ninety-percent (9 of ...200919070640
growth of an rna virus in single cells reveals a broad fitness distribution.genetic and environmental factors will influence the growth of an rna virus, but their relative contributions are challenging to resolve because standard culture methods mask how virus particles interact with individual host cells. here, single particles of vesicular stomatitis virus, a prototype rna virus, were used to infect individual bhk cells. infected cells produced 50 to 8000 progeny virus particles, but these differences were lost upon subsequent culture, suggesting the diversity of yiel ...200919070881
opposing effects of inhibiting cap addition and cap methylation on polyadenylation during vesicular stomatitis virus mrna synthesis.the multifunctional large (l) polymerase protein of vesicular stomatitis virus (vsv) contains enzymatic activities essential for rna synthesis, including mrna cap addition and polyadenylation. we previously mapped amino acid residues g1154, t1157, h1227, and r1228, present within conserved region v (crv) of l, as essential for mrna cap addition. here we show that alanine substitutions to these residues also affect 3'-end formation. specifically, the cap-defective polymerases produced truncated t ...200919073725
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