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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
does the vesicular stomatitis virus really have a selective oncolytic effect in human cancer? 201019795451
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
targeting viral dsrna for antiviral prophylaxis.double-stranded (ds)rna in the infected cells is a trait shared by most if not all viruses. while humans have developed variable immune responses, viruses have also developed countermeasures to defeat dsrna-induced antiviral strategies. thus, we proposed a broad antiviral strategy to antagonize the countermeasures of viruses and bypass the dsrna-induced signals that are readily defeated by viruses. by rewiring the dsrna-binding proteins in the dsrna complex and reconnecting them to apoptosis sig ...201119880628
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
characterization of the structure of the phosphoprotein of chandipura virus, a negative stranded rna virus probing intratryptophan energy transfer using single and double tryptophan mutants.the phosphoprotein (p protein) of chandipura virus (chpv), a negative stranded rna virus, is involved in both transcription and replication phases of the viral life cycle. the two tryptophan (trp) residues of chpv, located at 105 and 135 respectively and two single trp mutants w135f and w105f and a double trp mutant w135f/w105f have been characterized by steady state and time-resolved fluorescence and phosphorescence at 298 k and 77 k. results indicate that trp135 is more buried with less polar ...201019895867
study of andes virus entry and neutralization using a pseudovirion system.andes virus (andv), a member of the hantavirus genus in the family bunyaviridae, causes an acute disease characteristic of new-world hantaviruses called hantavirus pulmonary syndrome (hps). hps is a highly pathogenic disease with a case-fatality rate of 40%. andv is the only hantavirus reported to spread directly from human-to-human. the aim of the present study was to develop a quantitative and high-throughput pseudovirion assay to study andv infection and neutralization in biosafety level 2 fa ...201019903496
some attenuated variants of vesicular stomatitis virus show enhanced oncolytic activity against human glioblastoma cells relative to normal brain cells.vesicular stomatitis virus (vsv) has been shown in laboratory studies to be effective against a variety of tumors, including malignant brain tumors. however, attenuation of vsv may be necessary to balance the potential toxicity toward normal cells, particularly when targeting brain tumors. here we compared 10 recombinant vsv variants resulting from different attenuation strategies. attenuations included gene shifting (vsv-p1-gfp/rfp), m protein mutation (vsv-m51), g protein cytoplasmic tail trun ...201019906910
attenuation of vesicular stomatitis virus encephalitis through microrna targeting.vesicular stomatitis virus (vsv) has long been regarded as a promising recombinant vaccine platform and oncolytic agent but has not yet been tested in humans because it causes encephalomyelitis in rodents and primates. recent studies have shown that specific tropisms of several viruses could be eliminated by engineering microrna target sequences into their genomes, thereby inhibiting spread in tissues expressing cognate micrornas. we therefore sought to determine whether microrna targets could b ...201019906911
viral mutagenesis as a means for generating novel proteins.we demonstrate that a mutation-prone virus engineered to express a foreign gene is an expedient means for generating novel mutant nonviral proteins in mammalian cells. using vesicular stomatitis virus to express a gene coding for a fluorescent dsred protein, a number of green mutant variants including a new variant not previously described were rapidly isolated from infected cells, sequenced, and cloned. similar methods may be useful in the development of physiologically sensitive fluorescent re ...201019906913
structure of the nucleoprotein binding domain of mokola virus phosphoprotein.mokola virus (mokv) is a nonsegmented, negative-sense rna virus that belongs to the lyssavirus genus and rhabdoviridae family. mokv phosphoprotein p is an essential component of the replication and transcription complex and acts as a cofactor for the viral rna-dependent rna polymerase. p recruits the viral polymerase to the nucleoprotein-bound viral rna (n-rna) via an interaction between its c-terminal domain and the n-rna complex. here we present a structure for this domain of mokv p, obtained ...201019906936
rna adenosine deaminase adar1 deficiency leads to increased activation of protein kinase pkr and reduced vesicular stomatitis virus growth following interferon treatment.two size forms of adar1 adenosine deaminase are known, one constitutively expressed (p110) and the other interferon (ifn)-induced (p150). to test the role of adar1 in viral infection, hela cells with adar1 stably knocked down and 293 cells overexpressing adar1 were utilized. overexpression of p150 adar1 had no significant effect on the yield of vesicular stomatitis virus. likewise, reduction of p110 and p150 adar1 proteins to less than approximately 10 to 15% of parental levels (adar1-deficient) ...201019913273
refined methods for propagating vesicular stomatitis virus vectors that are defective for g protein expression.propagation-defective vesicular stomatitis virus (vsv) vectors that encode a truncated g protein (vsv-gstem) or lack the g gene entirely (vsv-deltag) are attractive vaccine vectors because they are immunogenic, cannot replicate and spread after vaccination, and do not express many of the epitopes that elicit neutralizing anti-vsv immunity. to consider advancing non-propagating vsv vectors towards clinical assessment, scalable technology that is compliant with human vaccine manufacturing must be ...201019941901
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
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
cd4+ t cell regulation of cd25 expression controls development of short-lived effector cd8+ t cells in primary and secondary responses.both cd4(+) t cell help and il-2 have been postulated to "program" activated cd8(+) t cells for memory cell development. however, the linkage between these two signals has not been well elucidated. here we have studied effector and memory cd8(+) t cell differentiation following infection with three pathogens (listeria monocytogenes, vesicular stomatitis virus, and vaccinia virus) in the absence of both cd4(+) t cells and il-2 signaling. we found that expression of cd25 on antigen-specific cd8(+) ...201019966302
immunogenicity of viral vector, prime-boost siv vaccine regimens in infant rhesus macaques: attenuated vesicular stomatitis virus (vsv) and modified vaccinia ankara (mva) recombinant siv vaccines compared to live-attenuated siv.in a previously developed infant macaque model mimicking hiv infection by breast-feeding, we demonstrated that intramuscular immunization with recombinant poxvirus vaccines expressing simian immunodeficiency virus (siv) structural proteins provided partial protection against infection following oral inoculation with virulent siv. in an attempt to further increase systemic but also local antiviral immune responses at the site of viral entry, we tested the immunogenicity of different orally admini ...201019995539
cocal-pseudotyped lentiviral vectors resist inactivation by human serum and efficiently transduce primate hematopoietic repopulating cells.lentiviral vectors are established as efficient and convenient vehicles for gene transfer. they are almost always pseudotyped with the envelope glycoprotein of vesicular stomatitis virus (vsv-g) due to the high titers that can be achieved, their stability, and broad tropism. we generated a novel cocal vesiculovirus envelope glycoprotein plasmid and compared the properties of lentiviral vectors pseudotyped with cocal, vsv-g, and a modified feline endogenous retrovirus envelope glycoprotein (rd114 ...201019997089
evaluation of the immunogenicity of a recombinant glycoprotein-based chandipura vaccine in combination with commercially available dpt vaccine.chandipura virus (chpv) belongs to family rhabdovoridae and has emerged as an encephalitis causing pathogen with high mortality among pediatric population from three indian states. the recombinant glycoprotein (rgp) was shown to be an excellent vaccine candidate as evaluated in a murine model. as the disease is predominantly rural, to ensure maximum coverage for chandipura vaccine, an attempt was made to evaluate combination of rgp and a commercially available dpt vaccine (chp-dpt). when chp-dpt ...201020005854
site-specific attachment of palmitate or stearate to cytoplasmic versus transmembrane cysteines is a common feature of viral spike proteins.many glycoproteins of enveloped viruses are known to be "palmitoylated" at cysteines located either in the transmembrane region or in the cytoplasmic tail. although it was recognized early on that "palmitoylation" is not specific for this carbon chain, the exact fatty acid composition of s-acylated proteins has been difficult to determine. advancements in mass-spectrometry (ms) now allow one to quantify the fatty acids linked to single acylation sites. we report that g of vesicular stomatitis vi ...201020006369
importance of hydrogen bond contacts between the n protein and rna genome of vesicular stomatitis virus in encapsidation and rna synthesis.vesicular stomatitis virus (vsv) genomic rna encapsidated by the nucleocapsid (n) protein is the template for transcription and replication by the viral polymerase. we analyzed the 2.9-a structure of the vsv n protein bound to rna (t. j. green, x. zhang, g. w. wertz, and m. luo, science 313:357-360, 2006) and identified amino acid residues with the potential to interact with rna via hydrogen bonds. the contributions of these interactions to n protein function were investigated by individually su ...201020007268
single-cycle viral gene expression, rather than progressive replication and oncolysis, is required for vsv therapy of b16 melanoma.a fully intact immune system would be expected to hinder the efficacy of oncolytic virotherapy by inhibiting viral replication. simultaneously, however, it may also enhance antitumor therapy through initiation of proinflammatory, antiviral cytokine responses at the tumor site. the aim of this study was to investigate the role of a fully intact immune system on the antitumor efficacy of an oncolytic virus. in this respect, injection of oncolytic vesicular stomatitis virus (vsv) into subcutaneous ...201020016540
cloning of common carp socs-3 gene and its expression during embryogenesis, gh-transgene and viral infection.as a member of a newly discovered protein family, the suppressor of cytokine signalling 3 (socs-3) has been shown to regulate the responses of many immune cytokines in a negative auto-regulatory manner. the full-length cdna of common carp socs-3 was 1603 bp and contained a 630 bp open reading frame (orf) coding for a protein of 209 amino acids. carp socs-3 molecule was well conserved especially in the src homology 2 (sh2) and the socs box. the kinase inhibitory region (kir) and ess domains, upst ...201020025976
inhibition of type iii interferon activity by orthopoxvirus immunomodulatory proteins.the type iii interferon (ifn) family elicits an antiviral response that is nearly identical to that evoked by ifn-alpha/beta. however, these cytokines (known as ifn-lambda1, 2, and 3) signal through a distinct receptor, and thus may be resistant to the evasion strategies used by some viruses to avoid the ifn-alpha/beta response. orthopoxviruses are highly resistant to ifn-alpha/beta because they encode well-characterized immunomodulatory proteins that inhibit ifn activity. these include a secret ...201020038204
synthesis, cytotoxicity, antiviral activity and interferon inducing ability of 6-(2-aminoethyl)-6h-indolo[2,3-b]quinoxalines.new 6-(2-aminoethyl)-6h-indolo[2,3-b]quinoxalines were synthesized with high yields using bromoethylisatin and 6-(2-bromoethyl)-6h-indolo[2,3-b]quinoxaline as intermediates. these compounds were screened for the cytotoxicity, antiviral activity and interferon inducing ability. it was shown, that tested 6-(2-aminoethyl)-6h-indolo[2,3-b]quinoxalines are low toxic potent interferon inducers and antivirals. morpholine and 4-methyl-piperidine derivatives appeared as the most active antivirals and the ...201020056519
intracranial administration of p gene sirna protects mice from lethal chandipura virus encephalitis.in parts of india, chandipura virus (chpv) has emerged as an encephalitis causing pathogen in both epidemic and sporadic forms. this pediatric disease follows rapid course leading to 55-75% mortality. in the absence of specific treatment, effectiveness of rna interference (rnai) was evaluated.201020062542
vesicular stomatitis virus oncolysis is potentiated by impairing mtorc1-dependent type i ifn production.oncolytic viruses constitute a promising therapy against malignant gliomas (mgs). however, virus-induced type i ifn greatly limits its clinical application. the kinase mammalian target of rapamycin (mtor) stimulates type i ifn production via phosphorylation of its effector proteins, 4e-bps and s6ks. here we show that mouse embryonic fibroblasts and mice lacking s6k1 and s6k2 are more susceptible to vesicular stomatitis virus (vsv) infection than their wt counterparts as a result of an impaired t ...201020080710
peptide-derivatized dendrimers inhibit human cytomegalovirus infection by blocking virus binding to cell surface heparan sulfate.dendrimers are hyperbranched synthetic well-defined molecules with a number of potential applications, especially in relation to the need for new antiviral agents. one subclass of dendrimers are peptide-derivatized dendrimers which consist of a peptidyl branching core and covalently attached surface peptide functional units. few studies have addressed the potential uses of peptide dendrimers as direct-acting antiviral agents. here, we report on the ability of two peptide dendrimers, sb105 and sb ...201020083141
reduced hiv-1 long terminal repeat transcription in subjects with protective interferon regulatory factor-1 genotype: a potential mechanism mediating resistance to infection by hiv-1.we previously described the polymorphism in the interferon regulatory factor-1 (irf-1) gene as a novel correlate of resistance to hiv-1 infection in a kenyan female sex worker cohort. however, the underlying mechanisms likely mediating this association remained to be elucidated. the initiation of hiv-1 long terminal repeat (ltr) transcription in peripheral blood mononuclear cells (pbmcs) from subjects with different irf-1 haplotypes, representing protective, intermediate and the least protective ...201020100115
cell-specific targeting of lentiviral vectors mediated by fusion proteins derived from sindbis virus, vesicular stomatitis virus, or avian sarcoma/leukosis virus.the ability to efficiently and selectively target gene delivery vectors to specific cell types in vitro and in vivo remains one of the formidable challenges in gene therapy. we pursued two different strategies to target lentiviral vector delivery to specific cell types. in one of the strategies, vector particles bearing a membrane-bound stem cell factor sequence plus a separate fusion protein based either on sindbis virus strain tr339 glycoproteins or the vesicular stomatitis virus g glycoprotei ...201020100344
incongruent fitness landscapes, not tradeoffs, dominate the adaptation of vesicular stomatitis virus to novel host types.host radiation refers to the ability of parasites to adapt to new environments and expand or change their niches. adaptation to one specific environment may involve a loss in adaptation to a second environment. thus, fitness costs may impose limits to niche expansion and constitute the cost of specialization. several reports have addressed the cost of host radiation in vesicular stomatitis virus (vsv), but in some cases the experimental setup may have resulted in the overestimation of fitness co ...201020107014
the hr motif in the rna-dependent rna polymerase l protein of chandipura virus is required for unconventional mrna-capping activity.chandipura virus (chpv) is an emerging human pathogen associated with acute encephalitis and is related closely to vesicular stomatitis virus (vsv), a prototype rhabdovirus. here, we demonstrate that the rna polymerase l protein of chpv exhibits a vsv-like rna:gdp polyribonucleotidyltransferase (prntase) activity, which transfers the 5'-monophosphorylated (p-) viral mrna start sequence to gdp to produce a capped rna, and that the conserved hr motif in the chpv l protein is essential for the prnt ...201020107017
a confocal and electron microscopic comparison of interferon beta-induced changes in vesicular stomatitis virus infection of neuroblastoma and nonneuronal cells.vesicular stomatitis virus (vsv) replication is highly sensitive to interferon (ifn)-induced antiviral responses. pretreatment of sensitive cultured cells with ifnbeta results in a 10(4)-fold reduction in the release of infectious vsv particles. however, differences exist between the mechanisms of reduced infectious particle titers in cell lines of neuroblastoma and nonneuronal lineage. in l929-fibroblast-derived cells, using immunofluorescence confocal microscopy, infection under control condit ...201020113203
electroporation facilitates introduction of reporter transgenes and virions into schistosome eggs.the schistosome egg represents an attractive developmental stage at which to target transgenes because of the high ratio of germ to somatic cells, because the transgene might be propagated and amplified by infecting snails with the miracidia hatched from treated eggs, and because eggs can be readily obtained from experimentally infected rodents.201020126309
cryo-em model of the bullet-shaped vesicular stomatitis virus.vesicular stomatitis virus (vsv) is a bullet-shaped rhabdovirus and a model system of negative-strand rna viruses. through direct visualization by means of cryo-electron microscopy, we show that each virion contains two nested, left-handed helices: an outer helix of matrix protein m and an inner helix of nucleoprotein n and rna. m has a hub domain with four contact sites that link to neighboring m and n subunits, providing rigidity by clamping adjacent turns of the nucleocapsid. side-by-side int ...201020133572
histidine-mediated rna transfer to gdp for unique mrna capping by vesicular stomatitis virus rna polymerase.the rna-dependent rna polymerase l protein of vesicular stomatitis virus, a prototype of nonsegmented negative-strand (nns) rna viruses, forms a covalent complex with a 5'-phosphorylated viral mrna-start sequence (l-prna), a putative intermediate in the unconventional mrna capping reaction catalyzed by the rna:gdp polyribonucleotidyltransferase (prntase) activity. here, we directly demonstrate that the purified l-prna complex transfers prna to gdp to produce the capped rna (gpp-prna), indicating ...201020142503
coupling the inhibition of viral transduction with a positive fluorescence signal.cell-based assays for the inhibition of viral infections most commonly couple a positive signal (e.g., an increase in fluorescence) to the infection itself and not to its inhibition. when performing drug screens, compounds decreasing the signal are therefore considered as putative inhibitors. however, this approach can cause the selection of many false positives, since, for example, both killing of the host cell and inhibiting viral cell-entry results in the same signal. using a model system bas ...201020156147
viruses know more than one way to don a cap. 201020167804
enhanced oncolytic activity of vesicular stomatitis virus encoding sv5-f protein against prostate cancer.vesicular stomatitis virus has been investigated as an oncolytic agent for cancer therapy because it preferentially replicates in tumor but not in normal cells due to the lack of a robust interferon antiviral system in transformed cells. however, wild-type vesicular stomatitis virus can induce a strong systemic immunological response and replicate in the central nervous system, potentially limiting its clinical usefulness. we report the construction of the recombinant, replication restricted ves ...201020172545
vesicular stomatitis virus infects resident cells of the central nervous system and induces replication-dependent inflammatory responses.vesicular stomatitis virus (vsv) infection of mice via intranasal administration results in a severe encephalitis with rapid activation and proliferation of microglia and astrocytes. we have recently shown that these glial cells express rig-i and mda5, cytosolic pattern recognition receptors for viral rna. however, it is unclear whether vsv can replicate in glial cells or if such replication is required for their inflammatory responses. here we demonstrate that primary microglia and astrocytes a ...201020172575
genomic evolution of vesicular stomatitis virus strains with differences in adaptability.virus strains with a history of repeated genetic bottlenecks frequently show a diminished ability to adapt compared to strains that do not have such a history. these differences in adaptability suggest differences in either the rate at which beneficial mutations are produced, the effects of beneficial mutations, or both. we tested these possibilities by subjecting four populations (two controls and two mutants with lower adaptabilities) to multiple replicas of a regimen of positive selection and ...201020181701
induction of interferon and interferon signaling pathways by replication of defective interfering particle rna in cells constitutively expressing vesicular stomatitis virus replication proteins.we show here that replication of defective interfering (di) particle rna in hek293 cells stably expressing vesicular stomatitis virus (vsv) replication proteins potently activates interferon (ifn) and ifn signaling pathways through upregulation of ifn-beta promoter, ifn-stimulated response element (isre) promoter, and nf-kappab promoter activities. replication of di particle rna, not mere expression of the viral replication proteins, was found to be critical for induction of ifn and ifn signalin ...201020181705
potent vesicular stomatitis virus-based avian influenza vaccines provide long-term sterilizing immunity against heterologous challenge.the emergence in 1997 and continuance today of a highly lethal h5n1 avian influenza virus (aiv) causing human disease has raised concern about an impending pandemic and the need for a vaccine to prepare for such an occurrence. we previously generated an efficacious vesicular stomatitis virus (vsv)-based aiv vaccine expressing h5 hemagglutinin (ha) from the fifth genomic position of vsv (j. a. schwartz et al., virology 366:166-173, 2007). here we have generated and characterized vsv-based vaccine ...201020181720
genomics and structure/function studies of rhabdoviridae proteins involved in replication and transcription.some mammalian rhabdoviruses may infect humans, and also infect invertebrates, dogs, and bats, which may act as vectors transmitting viruses among different host species. the vizier programme, an eu-funded fp6 program, has characterized viruses that belong to the vesiculovirus, ephemerovirus and lyssavirus genera of the rhabdoviridae family to perform ground-breaking research on the identification of potential new drug targets against these rna viruses through comprehensive structural characteri ...201020188763
different potential of c-type lectin-mediated entry between marburg virus strains.the glycoproteins (gps) of filoviruses are responsible for virus entry into cells. it is known that gp interacts with cellular c-type lectins for virus attachment to cells. since primary target cells of filoviruses express c-type lectins, c-type lectin-mediated entry is thought to be a possible determinant of virus tropism and pathogenesis. we compared the efficiency of c-type lectin-mediated entry between marburg virus strains angola and musoke by using a vesicular stomatitis virus (vsv) pseudo ...201020219911
united virus: the oncolytic tag-team against cancer!there is an urgent need for innovative therapeutic strategies to treat aggressive metastatic cancers that are incurable with standard therapeutic approaches. novel treatment strategies like oncolytic virotherapy have led, in some cases, to impressive effects on disease progression in human trials, suggesting that approval of an oncolytic virus therapeutic is on the horizon. while combinations of oncolytic viruses with small molecules are already being tested and have shown promise, we propose th ...201020227326
synergistic interaction between oncolytic viruses augments tumor killing.a major barrier to all oncolytic viruses (ovs) in clinical development is cellular innate immunity, which is variably active in a spectrum of human malignancies. to overcome the heterogeneity of tumor response, we combined complementary ovs that attack cancers in distinct ways to improve therapeutic outcome. two genetically distinct viruses, vesicular stomatitis virus (vsv) and vaccinia virus (vv), were used to eliminate the risk of recombination. the combination was tested in a variety of tumor ...201020234341
tax1bp1 and a20 inhibit antiviral signaling by targeting tbk1-ikki kinases.induction of type i interferons by the transcription factor irf3 is essential in the initiation of antiviral innate immunity. activation of irf3 requires c-terminal phosphorylation by the upstream kinases tbk1-ikki, where irf3 phosphorylation promotes dimerization, and subsequent nuclear translocation to the ifnbeta promoter. recent studies have described the ubiquitin-editing enzyme a20 as a negative regulator of irf3 signaling by associating with tbk1-ikki; however, the regulatory mechanism of ...201020304918
the ubiquitin-specific protease 17 is involved in virus-triggered type i ifn signaling.viral infection initiates a series of signaling cascades that activate the transcription factors nuclear factor kappa b and interferon regulatory factor 3, which collaborate to induce transcription of genes for type i interferons (ifns) and other cytokines. here we report that the deubiquitinating enzyme ubiquitin-specific protease 17 (usp17) is required for virus-induced rig-i- and melanoma differentiation-associated protein-5 (mda5)-mediated type i ifn signaling. knockdown of endogenous usp17 ...201020368735
arthropod-borne viruses transmitted by phlebotomine sandflies in europe: a review.phlebotomine sandflies are known to transmit leishmaniases, bacteria and viruses that affect humans and animals in many countries worldwide. these sandfly-borne viruses are mainly the phlebovirus, the vesiculovirus and the orbivirus. some of these viruses are associated with outbreaks or human cases in the mediterranean europe. in this paper, the viruses transmitted by phlebotomine sandflies in europe (toscana virus, sicilian virus, sandfly fever naples virus) are reviewed and their medical impo ...201020403307
mast cells elicit proinflammatory but not type i interferon responses upon activation of tlrs by bacteria.balanced induction of proinflammatory and type i ifn responses upon activation of toll-like receptors (tlrs) determines the outcome of microbial infections and the pathogenesis of autoimmune and other inflammatory diseases. mast cells, key components of the innate immune system, are known for their debilitating role in allergy and autoimmunity. however, their role in antimicrobial host defenses is being acknowledged increasingly. how mast cells interact with microbes and the nature of responses ...201020421474
improvement of human interferon alpha secretion by lactococcus lactis.to improve the secretion and expression of human interferon alpha 2b (ifn) in lactococcus lactis, a synthetic pro-peptide, leisstcda (leiss), was fused to the n-terminus of ifn. this gave a higher secretion efficiency (12% vs. 5%) and yield (approximately 2.8-fold) of ifn. the signal peptide, sp(slpa) (slpa, an s-layer protein of lactobacillus brevis), was also tested to secrete ifn instead of sp(usp45) (usp45, the main secreted protein in l. lactis). this gave increased ifn secretion (approxima ...201020431909
identification and characterization of common carp (cyprinus carpio l.) granzyme a/k, a cytotoxic cell granule-associated serine protease.granzyme (gzm) is an important member of serine protease family, and key component in the specific and non-specific cell-mediated cytotoxicity. partial gzma/k cdna sequence of common carp (cyprinus carpio l.) was isolated from thymus cdna library by the method of suppression subtractive hybridization (ssh). subsequently, the full length cdna of carp gzma/k was obtained by means of 3' race and 5' race, respectively. the full length cdna of carp gzma/k was 1053 bp, consisting of a 5'-terminal untr ...201020451619
improvement and optimization of a multiplex real-time reverse transcription polymerase chain reaction assay for the detection and typing of vesicular stomatitis virus.an improvement to a previously reported real-time reverse transcription polymerase chain reaction (real-time rt-pcr) assay for the detection of vesicular stomatitis virus (vsv) is described. results indicate that the new assay is capable of detecting a panel of genetically representative strains of vsv present in north, central, and south america. the assay is specific for vsv and allows for simultaneous differentiation between vesicular stomatitis indiana virus and vesicular stomatitis new jers ...201020453220
a vesicular stomatitis virus-based hepatitis b virus vaccine vector provides protection against challenge in a single dose.as one of the world's most common infectious diseases, hepatitis b virus (hbv) is a serious worldwide public health problem, with hbv-associated liver disease accounting for more than half a million deaths each year. although there is an effective prophylactic vaccine currently available to prevent infection, it has a number of characteristics that are suboptimal: multiple doses are needed to induce long-lasting immunity, immunity declines over time, it does not elicit protection in some individ ...201020504927
cell cycle progression or translation control is not essential for vesicular stomatitis virus oncolysis of hepatocellular carcinoma.the intrinsic oncolytic specificity of vesicular stomatitis virus (vsv) is currently being exploited to develop alternative therapeutic strategies for hepatocellular carcinoma (hcc). identifying key regulators in diverse transduction pathways that define vsv oncolysis in cancer cells represents a fundamental prerequisite to engineering more effective oncolytic viral vectors and adjusting combination therapies. after having identified defects in the signalling cascade of type i interferon inducti ...201020539760
[expression of porcine interferon-gamma and its safe antiviral assay].in order to ensure the biosafty of the ifn-gamma antiviral activity assay, we used a replication-deficient vsv carrying gfp as an interferon sensitive indicator virus (vsvdeltag*g). the antiviral activities of porcine ifn-gamma expressed in escherichia coli and in baculovirus on mdbk cells were assessed. the results showed that the antiviral activity of porcine ifn-gamma expressed in baculovirus could reach 10(5) iu/ml, while the porcine ifn-gamma expressed in e. coli showed some antiviral activ ...201020575430
subcapsular sinus macrophages prevent cns invasion on peripheral infection with a neurotropic virus.lymph nodes (lns) capture microorganisms that breach the body's external barriers and enter draining lymphatics, limiting the systemic spread of pathogens. recent work has shown that cd11b(+)cd169(+) macrophages, which populate the subcapsular sinus (scs) of lns, are critical for the clearance of viruses from the lymph and for initiating antiviral humoral immune responses. here we show, using vesicular stomatitis virus (vsv), a relative of rabies virus transmitted by insect bites, that scs macro ...201020577213
cell type mediated resistance of vesicular stomatitis virus and sendai virus to ribavirin.ribavirin (rbv) is a synthetic nucleoside analog with broad spectrum antiviral activity. although rbv is approved for the treatment of hepatitis c virus, respiratory syncytial virus, and lassa fever virus infections, its mechanism of action and therapeutic efficacy remains highly controversial. recent reports show that the development of cell-based resistance after continuous rbv treatment via decreased rbv uptake can greatly limit its efficacy. here, we examined whether certain cell types are n ...201020582319
the clinically approved proteasome inhibitor ps-341 efficiently blocks influenza a virus and vesicular stomatitis virus propagation by establishing an antiviral state.recently it has been shown that the proinflammatory nf-kappab pathway promotes efficient influenza virus propagation. based on these findings, it was suggested that nf-kappab blockade may be a promising approach for antiviral intervention. the classical virus-induced activation of the nf-kappab pathway requires proteasomal degradation of the inhibitor of nf-kappab, ikappab. therefore, we hypothesized that inhibition of proteasomal ikappab degradation should impair influenza a virus (iav) replica ...201020592098
distinct macrophage subpopulations regulate viral encephalitis but not viral clearance in the cns.intranasal application of vesicular stomatitis virus (vsv) induces acute encephalitis characterized by a pronounced myeloid and t cell infiltrate. the role of distinct phagocytic populations on vsv encephalitis was therefore examined in this study. ablation of peripheral macrophages did not impair vsv encephalitis or viral clearance from the brain, whereas, depletion of splenic marginal dendritic cells impaired this response and enhanced morbidity/mortality. selective depletion of brain perivasc ...201020599280
a laboratory-attenuated vesicular stomatitis virus induces apoptosis and alters the cellular microrna expression profile in bhk cells.in the present study, we characterized the pathways by which a laboratory-attenuated vesicular stomatitis virus (la-vsv) induces apoptosis in bhk cells. it was found that la-vsv induced a loss of mitochondrial membrane potential (δψm) and activated caspase-9 and -3, but not caspase-8, indicating that the induction of apoptosis by la-vsv may involve an intrinsic apoptotic pathway. although aberrant expression of micrornas (mirnas) has been linked to viral infection, little is known about changes ...201020625776
fusion-active glycoprotein g mediates the cytotoxicity of vesicular stomatitis virus m mutants lacking host shut-off activity.the cytopathogenicity of vesicular stomatitis virus (vsv) has been attributed mainly to the host shut-off activity of the viral matrix (m) protein, which inhibits both nuclear transcription and nucleocytoplasmic rna transport, thereby effectively suppressing the synthesis of type i interferon (ifn). the m protein from persistently vsv-infected cells was shown to harbour characteristic amino acid substitutions (m51r, v221f and s226r) implicated in ifn induction. this study demonstrates that infec ...201020631091
role of evolved host breadth in the initial emergence of an rna virus.understanding how evolution promotes pathogen emergence would aid disease management, and prediction of future host shifts. increased pathogen infectiousness of different hosts may occur through direct selection, or fortuitously via indirect selection. however, it is unclear which type of selection tends to produce host breadth promoting pathogen emergence. we predicted that direct selection for host breadth should foster emergence by causing higher population growth on new hosts, lower among-po ...201020633045
a spatio-temporal analysis of matrix protein and nucleocapsid trafficking during vesicular stomatitis virus uncoating.to study vsv entry and the fate of incoming matrix (m) protein during virus uncoating we used recombinant viruses encoding m proteins with a c-terminal tetracysteine tag that could be fluorescently labeled using biarsenical (lumio) compounds. we found that uncoating occurs early in the endocytic pathway and is inhibited by expression of dominant-negative (dn) rab5, but is not inhibited by dn-rab7 or dn-rab11. uncoating, as defined by the separation of nucleocapsids from m protein, occurred betwe ...201020657818
prospects for immunisation against marburg and ebola viruses.for more than 30 years the filoviruses, marburg virus and ebola virus, have been associated with periodic outbreaks of hemorrhagic fever that produce severe and often fatal disease. the filoviruses are endemic primarily in resource-poor regions in central africa and are also potential agents of bioterrorism. although no vaccines or antiviral drugs for marburg or ebola are currently available, remarkable progress has been made over the last decade in developing candidate preventive vaccines again ...201020658513
characterization of antibodies induced by vaccination with hepatitis c virus envelope glycoproteins.hepatitis c virus (hcv) envelope glycoproteins e1 and e2 were used with mf59 adjuvant as a candidate vaccine for a phase 1 safety and immunogenicity trial. ten of 41 vaccinee serum samples displayed a neutralization titer of > or =1:20 against vesicular stomatitis virus (vsv)-hcv pseudotype, 15 of 36 serum samples tested had a neutralization titer of > or =1:400 against human immunodeficiency virus (hiv)-hcv pseudotype, and 10 of 36 serum samples tested had a neutralization titer of > or =1:20 a ...201020677942
in vitro evaluation of marine-microorganism extracts for anti-viral activity.viral-induced infectious diseases represent a major health threat and their control remains an unachieved goal, due in part to the limited availability of effective anti-viral drugs and measures. the use of natural products in drug manufacturing is an ancient and well-established practice. marine organisms are known producers of pharmacological and anti-viral agents. in this study, a total of 20 extracts from marine microorganisms were evaluated for their antiviral activity. these extracts were ...201020691099
[antiviral effect of cerium dioxide nanoparticles stabilized by low-molecular polyacrylic acid].antiviral activity of nanosize cerium dioxide sols (ceo2) in animal cell culture has been studied. the inhibiting effect of the mentioned sols upon reproduction of vesicular stomatitis test-virus was demonstrated for the first time in case of preliminary 24-hour contact with cells lines l929 and ept. the effectiveness of protective action depends on initial precursor and the way of obtained water nanosize nanosols.201020695228
envelope-modified single-cycle simian immunodeficiency virus selectively enhances antibody responses and partially protects against repeated, low-dose vaginal challenge.immunization of rhesus macaques with strains of simian immunodeficiency virus (siv) that are limited to a single cycle of infection elicits t-cell responses to multiple viral gene products and antibodies capable of neutralizing lab-adapted siv, but not neutralization-resistant primary isolates of siv. in an effort to improve upon the antibody responses, we immunized rhesus macaques with three strains of single-cycle siv (scsiv) that express envelope glycoproteins modified to lack structural feat ...201020702641
generation of vsv pseudotypes using recombinant δg-vsv for studies on virus entry, identification of entry inhibitors, and immune responses to vaccines.vesicular stomatitis virus (vsv) is a prototypic enveloped animal virus that has been used extensively to study virus entry, replication and assembly due to its broad host range and robust replication properties in a wide variety of mammalian and insect cells. studies on vsv assembly led to the creation of a recombinant vsv in which the glycoprotein (g) gene was deleted. this recombinant (rvsv-δg) has been used to produce vsv pseudotypes containing the envelope glycoproteins of heterologous viru ...201020709108
chandipura virus - what we know & do not know. 201020716812
chandipura virus growth kinetics in vertebrate cell lines, insect cell lines & embryonated eggs.since not much information on chandipura virus is available, an attempt was made to study the growth kinetics of the virus in certain vertebrate, invertebrate cell lines and embryonated chicken eggs.201020716815
susceptibility of breast cancer cells to an oncolytic matrix (m) protein mutant of vesicular stomatitis virus.matrix (m) protein mutants of vesicular stomatitis virus (vsv), such as rm51r-m virus, are attractive candidates as oncolytic viruses for tumor therapies because of their capacity to selectively target cancer cells. the effectiveness of rm51r-m virus as an antitumor agent for the treatment of breast cancer was assessed by determining the ability of rm51r-m virus to infect and kill breast cancer cells in vitro and in vivo. several human- and mouse-derived breast cancer cell lines were susceptible ...201020725101
elucidation of functional domains of chandipura virus nucleocapsid protein involved in oligomerization and rna binding: implication in viral genome encapsidation.chandipura virus, a member of the vesiculovirus genera, has been recently recognized as an emerging human pathogen. previously, we have shown that chandipura virus nucleocapsid protein n is capable of binding to both specific viral leader rna as well as non-viral rna sequences, albeit in distinct monomeric and oligomeric states, respectively. here, we distinguish the regions of n involved in oligomerization and rna binding using a panel of deletion mutants. we demonstrate that deletion in the n- ...201020727566
the cytoplasmic location of chicken mx is not the determining factor for its lack of antiviral activity.chicken mx belongs to the mx family of interferon-induced dynamin-like gtpases, which in some species possess potent antiviral properties. conflicting data exist for the antiviral capability of chicken mx. reports of anti-influenza activity of alleles encoding an asn631 polymorphism have not been supported by subsequent studies. the normal cytoplasmic localisation of chicken mx may influence its antiviral capacity. here we report further studies to determine the antiviral potential of chicken mx ...201020808435
efficient inhibition of c-26 colon carcinoma by vsvmp gene delivered by biodegradable cationic nanogel derived from polyethyleneimine.biodegradable cationic nanoparticles have promising application as a gene delivery system. in this article, heparin-polyethyleneimine (hpei) nanogels were prepared, and these nanogels were developed as a nonviral gene vector. the transfection efficiency of hpei nanogels was comparable with that of pei25k, while the cytotoxicity was lower than that of pei2k and much lower than that of pei25k in vitro. these hpei nanogels also had better blood compatibility than pei25k. after intravenous administr ...201020839784
vsv oncolysis in combination with the bcl-2 inhibitor obatoclax overcomes apoptosis resistance in chronic lymphocytic leukemia.in chronic lymphocytic leukemia (cll), overexpression of antiapoptotic b-cell leukemia/lymphoma 2 (bcl-2) family members contributes to leukemogenesis by interfering with apoptosis; bcl-2 expression also impairs vesicular stomatitis virus (vsv)-mediated oncolysis of primary cll cells. in the effort to reverse resistance to vsv-mediated oncolysis, we combined vsv with obatoclax (gx15-070)-a small-molecule bcl-2 inhibitor currently in phase 2 clinical trials-and examined the molecular mechanisms g ...201020842105
specific detection of rinderpest virus by real-time reverse transcription-pcr in preclinical and clinical samples from experimentally infected cattle.a highly sensitive detection test for rinderpest virus (rpv), based on a real-time reverse transcription-pcr (rrt-pcr)system, was developed. five different rpv genomic targets were examined, and one was selected and optimized to detect viral rna in infected tissue culture fluid with a level of detection ranging from 0.59 to 87.5 50% tissue culture infectious doses (tcid(50)) per reaction depending on the viral isolate. the strain sensitivity of the test was validated on 16 rpv strains belonging ...201020844216
novel inhibitor of influenza non-structural protein 1 blocks multi-cycle replication in an rnase l-dependent manner.influenza virus non-structural protein 1 (ns1) is the centrepiece of the viral response to the host interferon (ifn) system. ns1 has been demonstrated previously to be a potential therapeutic target for antiviral therapy by identification of specific small-molecule inhibitors. this study demonstrated the biological mechanism for a potent new ns1 antagonist. compound jj3297 inhibited virus replication by more than three orders of magnitude without affecting cell viability. importantly, it efficie ...201020881091
ebolavirus is internalized into host cells via macropinocytosis in a viral glycoprotein-dependent manner.ebolavirus (ebov) is an enveloped, single-stranded, negative-sense rna virus that causes severe hemorrhagic fever with mortality rates of up to 90% in humans and nonhuman primates. previous studies suggest roles for clathrin- or caveolae-mediated endocytosis in ebov entry; however, ebolavirus virions are long, filamentous particles that are larger than the plasma membrane invaginations that characterize clathrin- or caveolae-mediated endocytosis. the mechanism of ebov entry remains, therefore, p ...201020886108
population dynamics of an rna virus and its defective interfering particles in passage cultures.viruses can fall prey to their defective interfering (di) particles. when viruses are cultured by serial passage on susceptible host cells, the presence of virus-like di particles can cause virus populations to rise and fall, reflecting predator-prey interactions between di and virus particles. the levels of virus and di particles in each population passage can be determined experimentally by plaque and yield-reduction assays, respectively.201020920247
memory t cells persisting within the brain after local infection show functional adaptations to their tissue of residence.the brain is not routinely surveyed by lymphocytes and is defined as an immuno-privileged site. however, viral infection of the brain results in the infiltration and long-term persistence of pathogen-specific cd8(+) t cells. these cells survive without replenishment from the circulation and are referred to as resident memory t cells (trm). brain trm selectively express the integrin cd103, the expression of which is dependent on antigen recognition within the tissue. after clearance of virus, cd8 ...201020923878
inducible microrna-155 feedback promotes type i ifn signaling in antiviral innate immunity by targeting suppressor of cytokine signaling 1.effective recognition of viral infection and subsequent triggering of antiviral innate immune responses are essential for the host antiviral defense, which is tightly regulated by multiple regulators, including micrornas. our previous study showed that a panel of micrornas, including mir-155, was markedly upregulated in macrophages upon vesicular stomatitis virus infection; however, the biological function of mir-155 during viral infection remains unknown. in this paper, we show that rna virus i ...201020937844
the matrix protein of vesicular stomatitis virus binds dynamin for efficient viral assembly.matrix proteins (m) direct the process of assembly and budding of viruses belonging to the mononegavirales order. using the two-hybrid system, the amino-terminal part of vesicular stomatitis virus (vsv) m was shown to interact with dynamin pleckstrin homology domain. this interaction was confirmed by coimmunoprecipitation of both proteins in cells transfected by a plasmid encoding a c-myc-tagged dynamin and infected by vsv. a role for dynamin in the viral cycle (in addition to its role in virion ...201020943988
identification of aromatic amino acid residues in conserved region vi of the large polymerase of vesicular stomatitis virus is essential for both guanine-n-7 and ribose 2'-o methyltransferases.non-segmented negative-sense rna viruses possess a unique mechanism for mrna cap methylation. for vesicular stomatitis virus, conserved region vi in the large (l) polymerase protein catalyzes both guanine-n-7 (g-n-7) and ribose 2'-o (2'-o) methyltransferases, and the two methylases share a binding site for the methyl donor s-adenosyl-l-methionine. unlike conventional mrna cap methylation, the 2'-o methylation of vsv precedes subsequent g-n-7 methylation. in this study, we found that individual a ...201020961592
chandipura virus encephalitis outbreak among children in nagpur division, maharashtra, 2007.an outbreak of acute encephalitis syndrome (aes) among children from nagpur division, maharashtra was investigated to confirm the aetiology and to describe clinico-epidemiological features.201020966517
rnai-mediated immunity provides strong protection against the negative-strand rna vesicular stomatitis virus in drosophila.activation of innate antiviral responses in multicellular organisms relies on the recognition of structural differences between viral and cellular rnas. double-stranded (ds)rna, produced during viral replication, is a well-known activator of antiviral defenses and triggers interferon production in vertebrates and rnai in invertebrates and plants. previous work in mammalian cells indicates that negative-strand rna viruses do not appear to generate dsrna, and that activation of innate immunity is ...201020978209
molecular architecture of the vesicular stomatitis virus rna polymerase.nonsegmented negative-strand (nns) rna viruses initiate infection by delivering into the host cell a highly specialized rna synthesis machine comprising the genomic rna completely encapsidated by the viral nucleocapsid protein and associated with the viral polymerase. the catalytic core of this protein-rna complex is a 250-kda multifunctional large (l) polymerase protein that contains enzymatic activities for nucleotide polymerization as well as for each step of mrna cap formation. working with ...201021041632
a morphological screening of protein crystals for interferon delivery by metal ion-chelate technology.this study presents a preliminary exploration on extending the half-life of therapeutic proteins by crystallization strategy without new molecular entities generation.201021050135
c-type lectins do not act as functional receptors for filovirus entry into cells.cellular c-type lectins have been reported to facilitate filovirus infection by binding to glycans on filovirus glycoprotein (gp). however, it is not clearly known whether interaction between c-type lectins and gp mediates all the steps of virus entry (i.e., attachment, internalization, and membrane fusion). in this study, we generated vesicular stomatitis viruses pseudotyped with mutant gps that have impaired structures of the putative receptor binding regions and thus reduced ability to infect ...201021056544
production of human interferon alfa 2b in plants of nicotiana excelsior by agrobacterium-mediated transient expression.human interferon alpha2b gene was transiently expressed in nicotiana excelsior plants. fusion with n. plumbaginifolia calreticulin signal peptide for improved apoplast targeting and carrying out the expression under optimized conditions resulted in maximal interferon activity of 3.2 x 10(3) iu/g fresh weight (fw) with an average of 2.1 +/- 0.8 x 10(3) iu/g fw. it proves that n. excelsior is a suitable host for agrobacterium-mediated transient expression of genes encoding physiologically active h ...201021058531
domain within the c protein of human parainfluenza virus type 3 that regulates interferon signaling.human parainfluenza virus type 3 (hpiv3), one of the paramyxoviruses, uses its accessory c protein as an antagonist against interferon (ifn)-mediated host innate immunity. we have previously shown that the c protein significantly decreased the ifn-induced phosphorylation of signal transducer and activator of transcription (stat) 1 and the formation of gamma ifn activation factor (gaf) complex, thus abrogating the antiviral activity of the ifns against vesicular stomatitis virus (vsv) replication ...201021061916
the anti-tumor agent, 5,6-dimethylxanthenone-4-acetic acid (dmxaa), induces ifn-beta-mediated antiviral activity in vitro and in vivo.the 2009 outbreak of pandemic h1n1 influenza, increased drug resistance, and the significant delay in obtaining adequate numbers of vaccine doses have heightened awareness of the need to develop new antiviral drugs that can be used prophylactically or therapeutically. previously, we showed that the experimental anti-tumor drug dmxaa potently induced ifn-β but relatively low tnf-α expression in vitro. this study confirms these findings in vivo and demonstrates further that dmxaa induces potent an ...201021084628
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