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rna interference screen for human genes associated with west nile virus infection.west nile virus (wnv), and related flaviviruses such as tick-borne encephalitis, japanese encephalitis, yellow fever and dengue viruses, constitute a significant global human health problem. however, our understanding of the molecular interaction of such flaviviruses with mammalian host cells is limited. wnv encodes only 10 proteins, implying that it may use many cellular proteins for infection. wnv enters the cytoplasm through ph-dependent endocytosis, undergoes cycles of translation and replic ...200818690214
cigarette smoking products suppress anti-viral effects of type i interferon via phosphorylation-dependent downregulation of its receptor.while negative effect of smoking on the resistance to viral infections was known, the underlying mechanisms remained unclear. here we report that products of cigarette smoking compromise the cellular anti-viral defenses by inhibiting the signaling induced by type i interferon (ifn). cigarette smoking condensate (but not pure nicotine) stimulated specific serine phosphorylation-dependent ubiquitination and degradation of the ifnar1 subunit of the type i ifn receptor leading to attenuation of ifn ...200818722370
formation of bovine viral diarrhea virus e1-e2 heterodimers is essential for virus entry and depends on charged residues in the transmembrane domains.the envelope of bovine viral diarrhea virus (bvdv) contains the glycoproteins erns, e1 and e2. complementation of a recombinant vesicular stomatitis virus (vsv) with bvdv glycoproteins resulted in infectious pseudotyped viruses. to elucidate the specific role of each of the single envelope glycoproteins during viral entry, pseudotypes were generated bearing the bvdv envelope proteins in different combinations. pseudoviruses that contained e1 and e2 but not erns were infectious, indicating that e ...200818753220
photodynamic treatment with mono-phenyl-tri-(n-methyl-4-pyridyl)-porphyrin for pathogen inactivation in cord blood stem cell products.hematopoietic stem cell transplants and culture of hematopoietic progenitor cells require pathogen-free conditions. the application of a method of pathogen inactivation in red blood cells using photodynamic treatment (pdt) was investigated for the decontamination of cord blood stem cell (cbsc) products.200818764827
severe acute respiratory syndrome coronavirus elicits a weak interferon response compared to traditional interferon-inducing viruses.the aim of the present study is to investigate changes of interferon (ifn) production occurring over the first 48 h after infection of peripheral blood mononuclear cells (pbmcs) with severe acute respiratory syndrome (sars) coronavirus (cov) and to compare these changes to those induced by well-established ifn-inducing viruses, such as vesicular stomatitis (vsv) and newcastle viruses (ndv). experiments have been carried out using pbmcs of 10 different healthy donors. the results showed that the ...200818781076
inhibition of the ifn-beta response in hepatocellular carcinoma by alternative spliced isoform of ifn regulatory factor-3.the intrinsic oncolytic specificity of vesicular stomatitis virus (vsv) is currently being exploited to develop alternative therapeutic strategies for hepatocellular carcinoma (hcc). we have observed earlier that, in contrast to cultured human hcc cells, primary human hepatocytes (phhs) are refractory to vsv infection. impairment of the type i interferon (ifn) pathway in hcc cells has been suggested to be the mechanism by which these cells become susceptible to vsv infection. the goal of this st ...200818781139
selection for gene junction sequences important for vsv transcription.the heptauridine tract at each gene end and intergenic region (igr) at the gene junctions of vesicular stomatitis virus (vsv) have effects on synthesis of the downstream mrna, independent of their respective roles in termination of the upstream mrna. to investigate the role of the u tract and the igr in downstream gene transcription, we altered the n/p gene junction of infectious vsv such that transcription levels would be affected and result in altered molar ratios of the n and p proteins, whic ...200818783810
detecting positively selected codons in the glycoprotein of spring viraemia of carp virus (svcv) isolates from the usa and china. 200818801064
dna vaccine protects ornamental koi (cyprinus carpio koi) against north american spring viremia of carp virus.the emergence of spring viremia of carp virus (svcv) in the united states constitutes a potentially serious alien pathogen threat to susceptible fish stocks in north america. a dna vaccine with an svcv glycoprotein (g) gene from a north american isolate was constructed. in order to test the vaccine a challenge model utilizing a specific pathogen-free domestic koi stock and a cold water stress treatment was also developed. we have conducted four trial studies demonstrating that the psgnc dna vacc ...200818812203
vesicular stomatitis virus matrix protein impairs cd1d-mediated antigen presentation through activation of the p38 mapk pathway.natural killer t (nkt) cells are unique t lymphocytes that recognize cd1d-bound lipid antigens and play an important role in both innate and acquired immune responses against infectious diseases and tumors. we have already shown that a vesicular stomatitis virus (vsv) infection results in the rapid inhibition of murine cd1d-mediated antigen presentation to nkt cells. in the present study, it was found that the vsv matrix (vsv-m) protein is an important element in this decrease in antigen present ...200818815300
chemical targeting of the innate antiviral response by histone deacetylase inhibitors renders refractory cancers sensitive to viral oncolysis.intratumoral innate immunity can play a significant role in blocking the effective therapeutic spread of a number of oncolytic viruses (ovs). histone deacetylase inhibitors (hdis) are known to influence epigenetic modifications of chromatin and can blunt the cellular antiviral response. we reasoned that pretreatment of tumors with hdis could enhance the replication and spread of ovs within malignancies. here, we show that hdis markedly enhance the spread of vesicular stomatitis virus (vsv) in a ...200818815361
the escrt-i subunit tsg101 controls endosome-to-cytosol release of viral rna.like other enveloped viruses, vesicular stomatitis virus infects cells through endosomes. there, the viral envelope undergoes fusion with endosomal membranes, thereby releasing the nucleocapsid into the cytoplasm and allowing infection to proceed. previously, we reported that the viral envelope fuses preferentially with the membrane of vesicles present within multivesicular endosomes. then, these intra-endosomal vesicles (containing nucleocapsids) are transported to late endosomes, where back-fu ...200818817529
use of biological therapy to enhance both virotherapy and adoptive t-cell therapy for cancer.to protect viral particles from neutralization, sequestration, nonspecific adhesion, and mislocalization following systemic delivery, we have previously exploited the natural tumor-homing properties of antigen-specific cd8+ t cells. thus, ot-i t cells, preloaded in vitro with the oncolytic vesicular stomatitis virus (vsv), can deliver virus to established b16ova tumors to generate significantly better therapy than that achievable with ot-i t cells, or systemically delivered vsv, alone. here, we ...200818827807
early steps of the virus replication cycle are inhibited in prostate cancer cells resistant to oncolytic vesicular stomatitis virus.vesicular stomatitis virus (vsv) is currently being studied as a candidate oncolytic virus for tumor therapies due to its potent tumoricidal activity. previous studies have demonstrated that vsv selectively infects tumor cells due to defects in their antiviral pathways. these defects make them more susceptible to vsv-induced killing than normal cells. however, some cancer cells display differential sensitivity to vsv. specifically, lncap prostate cancer cells are sensitive to infection with vsv, ...200818829743
s-adenosyl homocysteine-induced hyperpolyadenylation of vesicular stomatitis virus mrna requires the methyltransferase activity of l protein.there are many unique aspects of vesicular stomatitis virus (vsv) transcription. in addition to its unusual mrna capping and methyltransferase mechanisms, the addition of s-adenosyl homocysteine (sah), which is the by-product and competitive inhibitor of s-adenosyl methionine (sam)-mediated methyltransferase reactions, leads to synthesis of poly(a) tails on the 3' end of vsv mrnas that are 10- or 20-fold longer than normal. the mechanism by which this occurs is not understood, since it has been ...200818829753
a linear relationship between fitness and the logarithm of the critical bottleneck size in vesicular stomatitis virus populations.we explored the relationship between fitness change and population size during transmission in vesicular stomatitis populations of very high fitness. the results show a linear correlation between the logarithm of the critical bottleneck size (population size at which there are no significant fitness changes after 20 passages) and the initial fitness of the population. in addition, limits to fitness increases during large-population passages of very-high-fitness strains were abolished by increasi ...200818829755
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
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
fln29 deficiency reveals its negative regulatory role in the toll-like receptor (tlr) and retinoic acid-inducible gene i (rig-i)-like helicase signaling pathway.fln29 was identified as an interferon (ifn)-inducible gene, and it has been shown to suppress toll-like receptor 4-mediated nf-kappab activation by binding to traf6. to elucidate the physiological roles of fln29, we generated fln29-deficient mice. fln29 deficiency resulted in hyper-response to lps both in vivo and in vitro, demonstrating the negative regulatory role of fln29 in tlr4 signaling. furthermore, we found that fln29(-/-) mice exhibited increased susceptibility to poly(i:c)-induced sept ...200818849341
cigarette smoke attenuation of poly i:c-induced innate antiviral responses in human pbmc is mainly due to inhibition of ifn-beta production.the cellular response to dsrna or its synthetic analog polyinosinic-polycytidylic acid (poly i:c) results in irf-3-, irf-7- and nf-kb-mediated activation of type 1 ifns and pro-inflammatory cytokines critical for innate antiviral immune responses. to investigate whether cigarette smoke compromises type 1 ifn signaling in humans, peripheral blood mononuclear cells (pbmcs) from non-smoking individuals were treated with smoke-conditioned media (scm) and stimulated with poly i:c. we observed a marke ...200918930547
immune response during acute chandipura viral infection in experimentally infected susceptible mice.age dependent susceptibility was observed in chandipura virus (chpv) infected mice through intravenous and intraperitoneal route. adult mice were susceptible only through intracerebral route of infection. immature neuron and some other biological variables including immature immune system are considered to be important factor for age related susceptibility in some diseases. as chandipura virus infects both young and adult mice brain through intracerebral route the role of immune system during pe ...200818937835
the p14 fast protein of reptilian reovirus increases vesicular stomatitis virus neuropathogenesis.the fusogenic orthoreoviruses express nonstructural fusion-associated small transmembrane (fast) proteins that induce cell-cell fusion and syncytium formation. it has been speculated that the fast proteins may serve as virulence factors by promoting virus dissemination and increased or altered cytopathology. to directly test this hypothesis, the gene encoding the p14 fast protein of reptilian reovirus was inserted into the genome of a heterologous virus that does not naturally form syncytia, ves ...200918971262
host cell factors and functions involved in vesicular stomatitis virus entry.vesicular stomatitis virus (vsv) is an animal virus that based on electron microscopy and its dependence on acidic cellular compartments for infection is thought to enter its host cells in a clathrin-dependent manner. the exact cellular mechanism, however, is largely unknown. in this study, we characterized the entry kinetics of vsv and elucidated viral requirements for host cell factors during infection in hela cells. we found that endocytosis of vsv was a fast process with a half time of 2.5 t ...200918971266
characterization of retinoic acid-inducible gene-i expression in primary murine glia following exposure to vesicular stomatitis virus.vesicular stomatitis virus (vsv) is a negative-sense single-stranded rna virus that closely resembles its deadly cousin, rabies virus. in mice, vsv elicits a rapid and severe t cell-independent encephalitis, indicating that resident glial cells play an important role in the initiation of central nervous system (cns) inflammation. recently, retinoic acid-inducible gene i (rig-i)-like helicases have been shown to function as intracellular pattern recognition receptors for replicative viral rna mot ...200818991139
synergistic antitumor effects of transarterial viroembolization for multifocal hepatocellular carcinoma in rats.oncolytic virotherapy is a promising strategy for safe and effective treatment of malignancy. we have reported previously that recombinant vesicular stomatitis virus (vsv) vectors are effective oncolytic agents that can be safely administered via the hepatic artery in immunocompetent rats to treat multifocal hepatocellular carcinoma (hcc), resulting in tumor necrosis and prolonged survival. though the results were encouraging, complete tumor regression was not observed, which led us to explore a ...200819003878
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
screening of small-molecule compounds as inhibitors of hcv entry.the hepatitis c virus (hcv) has infected some 170 million people worldwide, and is expected to pose a significant medical problem for the foreseeable future. no vaccine is presently available, and the current antiviral therapies (pegylated interferon-alpha and ribavirin) are characterized by limited efficacy, high costs, and substantial side effects. initiation of infection requires attachment of the hcv virus to the cell surface followed by viral entry and represents a critical determinant of t ...200919009270
riplet/rnf135, a ring finger protein, ubiquitinates rig-i to promote interferon-beta induction during the early phase of viral infection.rig-i (retinoic acid-inducible gene-i), a cytoplasmic rna helicase, interacts with ips-1/mavs/cardif/visa, a protein on the outer membrane of mitochondria, to signal the presence of virus-derived rna and induce type i interferon production. activation of rig-i requires the ubiquitin ligase, trim25, which mediates lysine 63-linked polyubiquitination of the rig-i n-terminal card-like region. however, how this modification proceeds for activation of ips-1 by rig-i remains unclear. here we identify ...200919017631
tcr down-regulation controls virus-specific cd8+ t cell responses.the cd3gamma di-leucine-based motif plays a central role in tcr down-regulation. however, little is understood about the role of the cd3gamma di-leucine-based motif in physiological t cell responses. in this study, we show that the expansion in numbers of virus-specific cd8(+) t cells is impaired in mice with a mutated cd3gamma di-leucine-based motif. the cd3gamma mutation did not impair early tcr signaling, nor did it compromise recruitment or proliferation of virus-specific t cells, but it inc ...200819017968
gas-phase behavior of noncovalent transmembrane segment complexes.specific helix oligomerization between transmembrane segments (tmss) is often promoted by motifs like gxxxg. disruption of this motif in the transmembrane segments of vesicular stomatitis virus g-protein and of glycophorin a results in a reduced dimerization level studied by in vivo systems like toxr. this paper reports the influence of sequence motifs like gxxxg in solution and the gas phase.the transmembrane segments may behave differently in the gas and liquid phase, because of the absence of ...200819025888
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
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
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
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
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
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
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
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
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
[effect of apoptosis of vesicular stomatitis virus on tumor cells of nasopharyngeal carcinoma in vivo].to investigate apoptosis induced by vesicular stomatitis virus (vsv) in hne-1 cancer cells of human nasopharyngeal carcinoma by models of nude mice-balb/c in vivo.200819157153
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
internalization of swine vesicular disease virus into cultured cells: a comparative study with foot-and-mouth disease virus.we performed a comparative analysis of the internalization mechanisms used by three viruses causing important vesicular diseases in animals. swine vesicular disease virus (svdv) internalization was inhibited by treatments that affected clathrin-mediated endocytosis and required traffic through an endosomal compartment. svdv particles were found in clathrin-coated pits by electron microscopy and colocalized with markers of early endosomes by confocal microscopy. svdv infectivity was significantly ...200919225001
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
dideoxy fluoro-ketopyranosyl nucleosides as potent antiviral agents: synthesis and biological evaluation of 2,3- and 3,4-dideoxy-3-fluoro-4- and -2-keto-beta-d-glucopyranosyl derivatives of n(4)-benzoyl cytosine.the synthesis of the dideoxy fluoro ketopyranonucleoside analogues, 1-(2,3-dideoxy-3-fluoro-6-o-trityl-beta-d-glycero-hexopyranosyl-4-ulose)-n(4)-benzoyl cytosine (7a), 1-(3,4-dideoxy-3-fluoro-6-o-trityl-beta-d-glycero-hexopyranosyl-2-ulose)-n(4)-benzoyl cytosine (13a) and their detritylated analogues 8a and 14a, respectively, is described. condensation of peracetylated 3-deoxy-3-fluoro-d-glucopyranose (1) with silylated n(4)-benzoyl cytosine, followed by selective deprotection and isopropyliden ...200919246130
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
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
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
[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
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
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
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
reversal of papilloma growth in rabbits therapeutically vaccinated against e6 with naked dna and/or vesicular stomatitis virus vectors.persistent infection with high-risk human papillomaviruses (hpvs) is the greatest risk factor for the development of hpv-associated cancers. in this study rabbits bearing persistent and potentially malignant papillomas were used to test the efficacy of vaccination with a recombinant dna and/or vesicular stomatitis virus (vsv) targeting the cottontail rabbit papillomavirus (crpv) e6 protein. immune responses were primed with either vector and boosted twice with the homologous or heterologous e6 v ...201019615481
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
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
yak interferon-alpha loaded solid lipid nanoparticles for controlled release.to explore the potential of a novel animal interferon formulation for controlled release, the yak interferon-alpha (ifn-alpha) glutathione s-transferase (gst) fusion protein was expressed in escherichia coli (e. coli) and the purified recombinant ifn-alpha was encapsulated into solid lipid nanoparticles (sln) by double emulsion solvent evaporation (w/o/w) method. the particle size and zeta potential of ifn-alpha-loaded sln were 124.2+/-10.2 nm and -11.2+/-0.6 mv. the encapsulation efficiency of ...201019647842
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
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
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
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
evaluation of an attenuated vesicular stomatitis virus vector expressing interferon-beta for use in malignant pleural mesothelioma: heterogeneity in interferon responsiveness defines potential efficacy.abstract vesicular stomatitis virus (vsv) has shown promise as an oncolytic agent, although unmodified vsv can be neurotoxic. to avoid toxicity, a vector was created by introducing the interferon-beta (ifn-beta) gene (vsv.ifn-beta). we conducted this study to determine the ability of vsv.ifn-beta to lyse human cancer (mesothelioma) cells and to evaluate the potential of this recombinant virus for clinical translation. four normal human mesothelial and 12 mesothelioma cell lines were tested for t ...201019715403
peripheral immunization blocks lethal actions of vesicular stomatitis virus within the brain.vesicular stomatitis virus (vsv) is the prototype virus for 75 or more negative-strand rna viruses in the rhabdovirus family. some of these viruses, including vsv, can cause neurological impairment or death upon brain infection. vsv has shown promise in the prevention and treatment of disease as a vaccine vector and an oncolytic virus, but infection of the brain remains a concern. three vsv variants, the wild-type-related vsv-g/gfp and two attenuated viruses, vsv-ct1 and vsv-ct9-m51, were compar ...200919726512
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
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
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
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