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suppression of coronavirus replication by cyclophilin inhibitors.coronaviruses infect a variety of mammalian and avian species and cause serious diseases in humans, cats, mice, and birds in the form of severe acute respiratory syndrome (sars), feline infectious peritonitis (fip), mouse hepatitis, and avian infectious bronchitis, respectively. no effective vaccine or treatment has been developed for sars-coronavirus or fip virus, both of which cause lethal diseases. it has been reported that a cyclophilin inhibitor, cyclosporin a (csa), could inhibit the repli ...201323698397
enhanced arbovirus surveillance with deep sequencing: identification of novel rhabdoviruses and bunyaviruses in australian mosquitoes.viral metagenomics characterizes known and identifies unknown viruses based on sequence similarities to any previously sequenced viral genomes. a metagenomics approach was used to identify virus sequences in australian mosquitoes causing cytopathic effects in inoculated mammalian cell cultures. sequence comparisons revealed strains of liao ning virus (reovirus, seadornavirus), previously detected only in china, livestock-infecting stretch lagoon virus (reovirus, orbivirus), two novel dimarhabdov ...201324314645
insect antiviral innate immunity: pathways, effectors, and connections.insects are infected by a wide array of viruses some of which are insect restricted and pathogenic, and some of which are transmitted by biting insects to vertebrates. the medical and economic importance of these viruses heightens the need to understand the interaction between the infecting pathogen and the insect immune system in order to develop transmission interventions. the interaction of the virus with the insect host innate immune system plays a critical role in the outcome of infection. ...201324120681
the transmembrane domain and acidic lipid flip-flop regulates voltage-dependent fusion mediated by class ii and iii viral proteins.voltage dependence of fusion induced by class ii and class iii viral fusion proteins was investigated. class ii proteins from ross river and sindbus virus and a mutant class iii protein from epstein barr virus were found to induce cell-cell fusion that is voltage dependent. combined with previous studies, in all, four class ii and two class iii protein have now been shown to exhibit voltage-dependent fusion, demonstrating that this is probably a general phenomenon for these two classes of viral ...201324124539
the antiviral activities of isg15.post-translational protein modification is an important strategy for the regulation of the cell proteome independent of the need for new gene expression. ubiquitin and ubiquitin-like modifiers mediate the regulation of protein levels, signaling pathways, vesicular trafficking, and many other cellular processes through their covalent conjugation to proteins. interferon stimulated gene 15 (isg15) is a ubiquitin-like modifier induced by type i interferon. in addition to conjugating to potentially h ...201324095857
a fusion-inhibiting peptide against rift valley fever virus inhibits multiple, diverse viruses.for enveloped viruses, fusion of the viral envelope with a cellular membrane is critical for a productive infection to occur. this fusion process is mediated by at least three classes of fusion proteins (class i, ii, and iii) based on the protein sequence and structure. for rift valley fever virus (rvfv), the glycoprotein gc (class ii fusion protein) mediates this fusion event following entry into the endocytic pathway, allowing the viral genome access to the cell cytoplasm. here, we show that p ...201324069485
the enterohemorrhagic escherichia coli effector protein nlef binds mammalian tmp21.the human pathogens enterohemorrhagic and enteropathogenic escherichia coli (ehec and epec), as well as the mouse pathogen citrobacter rodentium encode type iii secretion system (t3ss) effector proteins to promote their survival in the infected host. the mechanisms of action and the host targets of t3ss effectors are under active investigation because of their importance to bacterial virulence. the non-locus of enterocyte effacement (lee)-encoded protein f, nlef, contributes to e. coli and c. ro ...201323434013
flaviviruses are sensitive to inhibition of thymidine synthesis pathways.dengue virus has emerged as a global health threat to over one-third of humankind. as a positive-strand rna virus, dengue virus relies on the host cell metabolism for its translation, replication, and egress. therefore, a better understanding of the host cell metabolic pathways required for dengue virus infection offers the opportunity to develop new approaches for therapeutic intervention. in a recently described screen of known drugs and bioactive molecules, we observed that methotrexate and f ...201323824813
heterogeneous nuclear ribonucleoprotein k supports vesicular stomatitis virus replication by regulating cell survival and cellular gene expression.the heterogeneous nuclear ribonucleoprotein k (hnrnp k) is a member of the family of hnrnps and was recently shown in a genome-wide small interfering rna (sirna) screen to support vesicular stomatitis virus (vsv) growth. to decipher the role of hnrnp k in vsv infection, we conducted studies which suggest that the protein is required for vsv spreading. virus binding to cells, entry, and nucleocapsid uncoating steps were not adversely affected in the absence of hnrnp k, whereas viral genome transc ...201323843646
erk signaling couples nutrient status to antiviral defense in the insect gut.a unique facet of arthropod-borne virus (arbovirus) infection is that the pathogens are orally acquired by an insect vector during the taking of a blood meal, which directly links nutrient acquisition and pathogen challenge. we show that the nutrient responsive erk pathway is both induced by and restricts disparate arboviruses in drosophila intestines, providing insight into the molecular determinants of the antiviral "midgut barrier." wild-type flies are refractory to oral infection by arboviru ...201323980175
understanding and altering cell tropism of vesicular stomatitis virus.vesicular stomatitis virus (vsv) is a prototypic nonsegmented negative-strand rna virus. vsv's broad cell tropism makes it a popular model virus for many basic research applications. in addition, a lack of preexisting human immunity against vsv, inherent oncotropism and other features make vsv a widely used platform for vaccine and oncolytic vectors. however, vsv's neurotropism that can result in viral encephalitis in experimental animals needs to be addressed for the use of the virus as a safe ...201323796410
do viruses require the cytoskeleton?it is generally thought that viruses require the cytoskeleton during their replication cycle. however, recent experiments in our laboratory with rubella virus, a member of the family togaviridae (genus rubivirus), revealed that replication proceeded in the presence of drugs that inhibit microtubules. this study was done to expand on this observation.201323597412
5-(perylen-3-yl)ethynyl-arabino-uridine (auy11), an arabino-based rigid amphipathic fusion inhibitor, targets virion envelope lipids to inhibit fusion of influenza virus, hepatitis c virus, and other enveloped viruses.entry of enveloped viruses requires fusion of viral and cellular membranes. fusion requires the formation of an intermediate stalk structure, in which only the outer leaflets are fused. the stalk structure, in turn, requires the lipid bilayer of the envelope to bend into negative curvature. this process is inhibited by enrichment in the outer leaflet of lipids with larger polar headgroups, which favor positive curvature. accordingly, phospholipids with such shape inhibit viral fusion. we previou ...201323283943
oncolytic vesicular stomatitis virus and bortezomib are antagonistic against myeloma cells in vitro but have additive anti-myeloma activity in vivo.multiple myeloma cells are highly sensitive to the oncolytic effects of vesicular stomatitis virus (vsv), which specifically targets and kills cancer cells. myeloma cells are also exquisitely sensitive to the cytotoxic effects of the clinically approved proteasome inhibitor bortezomib. therefore, we sought to determine whether the combination of vsv and bortezomib would enhance tumor cell killing. however, as shown here, combining these two agents in vitro results in antagonism. we show that bor ...201324067362
improved lentiviral transduction of als motoneurons in vivo via dual targeting.treatment of amyotrophic lateral sclerosis (als), a progressive neurodegenerative disease, is hampered by its complex etiology and lack of efficient means for targeted transfer of therapeutics into motoneurons. the objective of this research was engineering of a versatile motoneuron targeting adapter--a full-length atoxic tetanus toxin fused to core-streptavidin (cs-tetim)--for retro-axonal transduction of viral vectors; validation of the targeting efficiency of cs-tetim in vivo, by expression o ...201324066863
antigen-loaded ph-sensitive hydrogel microparticles are taken up by dendritic cells with no requirement for targeting antibodies.particle-based delivery of encapsulated antigens has great potential for improving vaccine constructs. in this study, we show that antigen-loaded, ph-sensitive hydrogel microparticles are taken up and presented by bone marrow-derived dendritic cells (bmdcs) in vitro and are taken up by dendritic cells (dcs) and monocytes in vivo. this uptake is irrespective of targeting antibodies. bmdcs in vitro and dcs in vivo also display upregulation of activation markers cd80 and cd86 when treated with micr ...201323060228
both antiviral activity and intracellular localization of chicken mx protein depend on a polymorphism at amino acid position 631.the mx protein is known to inhibit the multiplication of several rna viruses. in chickens, a polymorphism at amino acid position 631 (631 aa) of mx protein has been suggested to be involved in the antiviral ability against vesicular stomatitis virus (vsv) and influenza virus, indicating that a ser-to-asn substitution at 631 aa is the source of this antiviral ability. however, how the substitution at 631 aa contributes to the antiviral activity remains to be clarified. in this study, we investiga ...201323201406
phosphatidylinositol 3-phosphatase myotubularin-related protein 6 (mtmr6) is regulated by small gtpase rab1b in the early secretory and autophagic pathways.a large family of myotubularin phosphatases dephosphorylates phosphatidylinositol 3-phosphate and phosphatidylinositol 3,5-bisphosphate, which are known to play important roles in vesicular trafficking and autophagy. the family is composed of 16 members, and understanding their regulatory mechanisms is important to understand their functions and related genetic diseases. we prepared anti-myotubularin-related protein 6 (mtmr6) monoclonal antibody and used it to study the regulatory mechanism of m ...201323188820
expression and functional characterization of retinoic acid-inducible gene-i-like receptors of mast cells in response to viral infection.to investigate the precise mechanisms of virus recognition by mast cells, the expression and functional characteristics of virus recognition receptors that lead to mast cell activation were investigated. our results suggest that mast cells are partly responsible for the early in vivo production of antiviral cytokines and chemokines upon vesicular stomatitis virus (vsv) infection. analysis of the expression of double-stranded rna (dsrna) recognition receptors in murine bone marrow-derived mast ce ...201323171655
identification of stat2 serine 287 as a novel regulatory phosphorylation site in type i interferon-induced cellular responses.stat2 is a positive modulator of the transcriptional response to type i interferons (ifns). stat2 acquires transcriptional function by becoming tyrosine phosphorylated and imported to the nucleus following type i ifn receptor activation. although most stat proteins become dually phosphorylated on specific tyrosine and serine residues to acquire full transcriptional activity, no serine phosphorylation site in stat2 has been reported. to find novel phosphorylation sites, mass spectrometry of immun ...201323139419
highly attenuated recombinant vesicular stomatitis virus vsv-12'gfp displays immunogenic and oncolytic activity.vesicular stomatitis virus (vsv) has shown considerable promise both as an immunization vector and as an oncolytic virus. in both applications, an important concern is the safety profile of the virus. to generate a highly attenuated virus, we added two reporter genes to the 3' end of the vsv genome, thereby shifting the npmgl genes from positions 1 to 5 to positions 3 to 7. the resulting virus (vsv-12'gfp) was highly attenuated, generating smaller plaques than four other attenuated vsvs. in one- ...201323135719
differentially imprinted innate immunity by mucosal boost vaccination determines antituberculosis immune protective outcomes, independent of t-cell immunity.homologous and heterologous parenteral prime-mucosal boost immunizations have shown great promise in combating mucosal infections such as tuberculosis and aids. however, their immune mechanisms remain poorly defined. in particular, it is still unclear whether t-cell and innate immunity may be independently affected by these immunization modalities and how it impacts immune protective outcome. using two virus-based tuberculosis vaccines (adenovirus (ad) and vesicular stomatitis virus (vsv) vector ...201323131783
variation in susceptibility of human malignant melanomas to oncolytic vesicular stomatitis virus.vesicular stomatitis virus (vsv) is a novel, anti-cancer therapy that targets cancer cells selectively with defective antiviral responses; however, not all malignant cells are sensitive to the oncolytic effects of vsv. herein, we have explored the mechanistic determinants of mutant m protein vsv (m51r-vsv) susceptibility in malignant melanoma cells.201323102637
the efficacy versus toxicity profile of combination virotherapy and tlr immunotherapy highlights the danger of administering tlr agonists to oncolytic virus-treated mice.injection of oncolytic vesicular stomatitis virus (vsv) into established b16ova melanomas results in tumor regression, in large part by inducing innate immune reactivity against the viral infection, mediated by myd88- and type iii interferon (ifn)-, but not tlr-4-, signaling. we show here that intratumoral (it) treatment with lipopolysaccharide (lps), a tlr-4 agonist, significantly enhanced the local therapy induced by vsv by combining activation of different innate immune pathways. therapy was ...201323011032
stability and inactivation of vesicular stomatitis virus, a prototype rhabdovirus.viruses may remain infectious outside the host cell for considerable time and represent a source of accidental infection if not properly inactivated. in this study, the survival of vesicular stomatitis virus (vsv) in suspension and dried on surfaces was analyzed. in addition, the sensitivity of vsv to disinfectants and physicochemical changes was investigated. vsv showed a notable stability in suspension at 4°c with virus titers remaining high over several weeks. the presence of serum proteins h ...201322995872
using clinically approved cyclophosphamide regimens to control the humoral immune response to oncolytic viruses.oncolytic viruses can be neutralized in the bloodstream by antiviral antibodies whose titers increase progressively with each exposure, resulting in faster virus inactivation and further reductions in efficacy with each successive dose. a single dose of cyclophosphamide (cpa) at 370 mg m(-2) was not sufficient to control the primary antiviral immune responses in mice, squirrel monkeys and humans. we therefore tested clinically approved multidose cpa regimens, which are known to kill proliferatin ...201322476202
characterization of the envelope glycoprotein of a novel filovirus, lloviu virus.lloviu virus (llov), a novel filovirus detected in bats, is phylogenetically distinct from viruses in the genera ebolavirus and marburgvirus in the family filoviridae. while filoviruses are known to cause severe hemorrhagic fever in humans and/or nonhuman primates, llov is biologically uncharacterized, since infectious llov has never been isolated. to examine the properties of llov, we characterized its envelope glycoprotein (gp), which likely plays a key role in viral tropism and pathogenicity. ...201324131711
epizootic hemorrhagic disease in yaks (bos grunniens).an epizootic of hemorrhagic disease associated with epizootic hemorrhagic disease virus serotype 2 (ehdv-2) infections in yaks from 5 herds occurred in colorado between august 21 and october 3, 2012. affected yaks presented with fever, lethargy, anorexia, dyspnea, and swollen conjunctivae. ulcerated dental pads, mucoid sanguineous nasal discharge, petechial hemorrhages in multiple organs, pulmonary edema, and serosanguinous fluid in the thorax, abdomen, and pericardial sac were observed at necro ...201323572453
efficient heterologous antigen gene delivery and expression by a replication-attenuated bohv-4-based vaccine vector.bovine herpesvirus 4 (bohv-4) is a gammaherpesvirus belonging to the rhadinovirus genus and due to its biological characteristics has been proposed as a vaccine vector for veterinary vaccines. because viral vector-associated risk is a major concern for viral vector applications, attenuation is a desirable feature. therefore, efforts are directed toward the development of highly attenuated viral vectors. bohv-4 naturally exhibits limited pathogenicity and a further attenuation, in terms of replic ...201323830977
bovine herpesvirus 4 glycoprotein b is indispensable for lytic replication and irreplaceable by vsvg.bovine herpesvirus 4 (bohv-4) is a gammaherpesvirus, belonging to rhadinovirus genus, with no clear association with disease. however, there is increasing evidence of its secondary pathogenic role in cases of post-partum metritis in cattle. bohv-4 open reading frame 8 (orf8) codifies for glycoprotein b (gb) that shows a heterodimeric structure, composed of two subunits and covalently linked by disulfide bonds and responsible for host cell adhesion through binding to heparan sulfates associated w ...201323302472
differential sensitivity of bat cells to infection by enveloped rna viruses: coronaviruses, paramyxoviruses, filoviruses, and influenza viruses.bats (chiroptera) host major human pathogenic viruses including corona-, paramyxo, rhabdo- and filoviruses. we analyzed six different cell lines from either yinpterochiroptera (including african flying foxes and a rhinolophid bat) or yangochiroptera (genera carollia and tadarida) for susceptibility to infection by different enveloped rna viruses. none of the cells were sensitive to infection by transmissible gastroenteritis virus (tgev), a porcine coronavirus, or to infection mediated by the spi ...201324023659
in vitro antiviral activity of plant extracts from asteraceae medicinal plants.due to the high prevalence of viral infections having no specific treatment and the constant appearance of resistant viral strains, the development of novel antiviral agents is essential. the aim of this study was to evaluate the antiviral activity against bovine viral diarrhea virus, herpes simplex virus type 1 (hsv-1), poliovirus type 2 (pv-2) and vesicular stomatitis virus of organic (oe) and aqueous extracts (ae) from: baccharis gaudichaudiana, b. spicata, bidens subalternans, pluchea sagitt ...201323890410
the antiviral innate immune response in fish: evolution and conservation of the ifn system.innate immunity constitutes the first line of the host defense after pathogen invasion. viruses trigger the expression of interferons (ifns). these master antiviral cytokines induce in turn a large number of interferon-stimulated genes, which possess diverse effector and regulatory functions. the ifn system is conserved in all tetrapods as well as in fishes, but not in tunicates or in the lancelet, suggesting that it originated in early vertebrates. viral diseases are an important concern of fis ...201324075867
characterization of the properties of seven promoters in the motor cortex of rats and monkeys after lentiviral vector-mediated gene transfer.lentiviral vectors deliver transgenes efficiently to a wide range of neuronal cell types in the mammalian central nervous system. to drive gene expression, internal promoters are essential; however, the in vivo properties of promoters, such as their cell type specificity and gene expression activity, are not well known, especially in the nonhuman primate brain. here, the properties of five ubiquitous promoters (murine stem cell virus [mscv], cytomegalovirus [cmv], cmv early enhancer/chicken β-ac ...201323964981
vesicular stomatitis virus-based vaccines protect nonhuman primates against bundibugyo ebolavirus.ebola virus (ebov) causes severe and often fatal hemorrhagic fever in humans and nonhuman primates (nhps). currently, there are no licensed vaccines or therapeutics for human use. recombinant vesicular stomatitis virus (rvsv)-based vaccine vectors, which encode an ebov glycoprotein in place of the vsv glycoprotein, have shown 100% efficacy against homologous sudan ebolavirus (sebov) or zaire ebolavirus (zebov) challenge in nhps. in addition, a single injection of a blend of three rvsv vectors co ...201324367715
c-peptide inhibitors of ebola virus glycoprotein-mediated cell entry: effects of conjugation to cholesterol and side chain-side chain crosslinking.we previously described potent inhibition of ebola virus entry by a 'c-peptide' based on the gp2 c-heptad repeat region (chr) targeted to endosomes ('tat-ebo'). here, we report the synthesis and evaluation of c-peptides conjugated to cholesterol, and tat-ebo analogs containing covalent side chain-side chain crosslinks to promote α-helical conformation. we found that the cholesterol-conjugated c-peptides were potent inhibitors of ebola virus glycoprotein (gp)-mediated cell entry (~10(3)-fold redu ...201323962564
conformational properties of peptides corresponding to the ebolavirus gp2 membrane-proximal external region in the presence of micelle-forming surfactants and lipids.ebola virus and sudan virus are members of the family filoviridae of nonsegmented negative-strand rna viruses ("filoviruses") that cause severe hemorrhagic fever with fatality rates as high as 90%. infection by filoviruses requires membrane fusion between the host and the virus; this process is facilitated by the two subunits of the envelope glycoprotein, gp1 (the surface subunit) and gp2 (the transmembrane subunit). the membrane-proximal external region (mper) is a trp-rich segment that immedia ...201323650881
identification of a broad-spectrum inhibitor of viral rna synthesis: validation of a prototype virus-based approach.there are no approved therapeutics for the most deadly nonsegmented negative-strand (nns) rna viruses, including ebola (ebov). to identify chemical scaffolds for the development of broad-spectrum antivirals, we undertook a prototype-based lead identification screen. using the prototype nns virus, vesicular stomatitis virus (vsv), multiple inhibitory compounds were identified. three compounds were investigated for broad-spectrum activity and inhibited ebov infection. the most potent, cmldbu3402, ...201323521799
novel mutations in marburg virus glycoprotein associated with viral evasion from antibody mediated immune pressure.marburg virus (marv) and ebola virus, members of the family filoviridae, cause lethal haemorrhagic fever in humans and non-human primates. although the outbreaks are concentrated mainly in central africa, these viruses are potential agents of imported infectious diseases and bioterrorism in non-african countries. recent studies demonstrated that non-human primates passively immunized with virus-specific antibodies were successfully protected against fatal filovirus infection, highlighting the im ...201323288419
ten years of dengue drug discovery: progress and prospects.to combat neglected diseases, the novartis institute of tropical diseases (nitd) was founded in 2002 through private-public funding from novartis and the singapore economic development board. one of nitd's missions is to develop antivirals for dengue virus (denv), the most prevalent mosquito-borne viral pathogen. neither vaccine nor antiviral is currently available for denv. here we review the progress in dengue drug discovery made at nitd as well as the major discoveries made by academia and ot ...201324076358
soluble interleukin-6 receptor-mediated innate immune response to dna and rna viruses.the interleukin-6 (il-6) receptor, which exists as membrane-bound and soluble forms, plays critical roles in the immune response. the soluble il-6 receptor (sil6r) has been identified as a potential therapeutic target for preventing coronary heart disease. however, little is known about the role of this receptor during viral infection. in this study, we show that sil6r, but not il-6, is induced by viral infection via the cyclooxygenase-2 pathway. interestingly, sil6r, but not il-6, exhibited ext ...201323946454
microrna-548 down-regulates host antiviral response via direct targeting of ifn-λ1.interferon (ifn)-mediated pathways are a crucial part of the cellular response against viral infection. type iii ifns, which include ifn-λ1, 2 and 3, mediate antiviral responses similar to type i ifns via a distinct receptor complex. ifn-λ1 is more effective than the other two members. transcription of ifn-λ1 requires activation of irf3/7 and nuclear factor-kappa b (nf-κb), similar to the transcriptional mechanism of type i ifns. using reporter assays, we discovered that viral infection induced ...201323150165
development of a luminex assay for the detection of swine antibodies to non-structural proteins of foot-and-mouth disease virus.foot-and mouth disease (fmd), swine vesicular disease (svd), and vesicular stomatitis (vs) are highly contagious vesicular diseases of swine but are not easy to differentiate clinically. for the purpose of instant detecting of fmd and differentiating it from the other vesicular diseases, a luminex assay was developed. sera from 64 infected, 307 vaccinated, and 280 naïve pigs were tested by the luminex assay. diagnostic sensitivity of the assay was 100%. diagnostic specificity of the assay was 98 ...201323962586
engagement of soluble resistance-related calcium binding protein (sorcin) with foot-and-mouth disease virus (fmdv) vp1 inhibits type i interferon response in cells.foot-and-mouth disease (fmd) is an acute, highly contagious animal disease caused by fmd virus (fmdv). although fmdv-induced immunosuppression in host has been well established, the exact molecular mechanism for such induction is not very clear. we report here the identification of fmdv vp1 as an interferon-suppressor by interacting with soluble resistance-related calcium binding protein (sorcin). we found that vp1 suppressed tumor necrosis factor (tnf)-α or sendai virus (sev)-induced type i int ...201323764275
development and evaluation of multiplex rt-lamp assays for rapid and sensitive detection of foot-and-mouth disease virus.this paper describes the evaluation of four novel real-time multiplex reverse transcription loop-mediated isothermal amplification (rt-lamp) assays for rapid and sensitive diagnosis of foot-and-mouth disease (fmd). in order to overcome the genetic diversity of fmd viruses (fmdv), these multiplex rt-lamp assay pairs were established by combining four newly designed primer sets with two primer sets that had been previously published. using a real-time turbidimeter to detect amplification products ...201323583488
neuroattenuation of vesicular stomatitis virus through picornaviral internal ribosome entry sites.vesicular stomatitis virus (vsv) is potent and a highly promising agent for the treatment of cancer. however, translation of vsv oncolytic virotherapy into the clinic is being hindered by its inherent neurotoxicity. it has been demonstrated that selected picornaviral internal ribosome entry site (ires) elements possess restricted activity in neuronal tissues. we therefore sought to determine whether the picornavirus ires could be engineered into vsv to attenuate its neuropathogenicity. we have u ...201323283963
gene therapy for pids: progress, pitfalls and prospects.substantial progress has been made in the past decade in treating several primary immunodeficiency disorders (pids) with gene therapy. current approaches are based on ex-vivo transfer of therapeutic transgene via viral vectors to patient-derived autologous hematopoietic stem cells (hscs) followed by transplantation back to the patient with or without conditioning. the overall outcome from all the clinical trials targeting different pids has been extremely encouraging but not without caveats. mal ...201323566838
intrapulmonary versus nasal transduction of murine airways with gp64-pseudotyped viral vectors.persistent viral vector-mediated transgene expression in the airways requires delivery to cells with progenitor capacity and avoidance of immune responses. previously, we observed that gp64-pseudotyped feline immunodeficiency virus (fiv)-mediated gene transfer was more efficient in the nasal airways than the large airways of the murine lung. we hypothesized that in vivo gene transfer was limited by immunological and physiological barriers in the murine intrapulmonary airways. here, we systematic ...201323360952
translation of viral mrnas that do not require eif4e is blocked by the inhibitor 4egi-1.high throughput screening has rendered new inhibitors of eukaryotic protein synthesis. one such molecule, 4egi-1 has been reported to selectively block the initiation factor eif4e. we have investigated the action of this inhibitor on translation directed by several viral mrnas which, in principle, do not utilize eif4e. we found that 4egi-1 inhibits translation directed by poliovirus ires, in rabbit reticulocyte lysates, to a similar extent as capped mrna. moreover, 4egi-1 inhibits translation dr ...201323870416
inactivation of pathogenic viruses by plant-derived tannins: strong effects of extracts from persimmon (diospyros kaki) on a broad range of viruses.tannins, plant-derived polyphenols and other related compounds, have been utilized for a long time in many fields such as the food industry and manufacturing. in this study, we investigated the anti-viral effects of tannins on 12 different viruses including both enveloped viruses (influenza virus h3n2, h5n3, herpes simplex virus-1, vesicular stomatitis virus, sendai virus and newcastle disease virus) and non-enveloped viruses (poliovirus, coxsachievirus, adenovirus, rotavirus, feline calicivirus ...201323372851
in vitro inhibition of vesicular stomatitis virus replication by purified porcine mx1 protein fused to hiv-1 tat protein transduction domain (ptd).vesicular stomatitis virus (vsv) is the causative agent of vesicular stomatitis (vs), a highly contagious fatal disease of human and pigs. few effective antiviral drugs are currently available against vsv infection. mx proteins are interferon (ifn)-induced dynamin-like gtpases present in all vertebrates with a range of antiviral activities. previous studies have shown that the transfected cell lines expressing either porcine mx1 or human mxa acquired a high degree of resistance to vsv. to explor ...201323727591
specific inhibition of hepatitis c virus entry into host hepatocytes by fungi-derived sulochrin and its derivatives.hepatitis c virus (hcv) is a major causative agent of hepatocellular carcinoma. although various classes of anti-hcv agents have been under clinical development, most of these agents target rna replication in the hcv life cycle. to achieve a more effective multidrug treatment, the development of new, less expensive anti-hcv agents that target a different step in the hcv life cycle is needed. we prepared an in-house natural product library consisting of compounds derived from fungal strains isola ...201324099774
inhibition of hepatitis c virus infection by polyoxometalates.hepatitis c virus (hcv) infects about 2% of the world population. the standard treatment of chronic hcv infection is still discontented because of the low sustained virological response rate. the development of new hcv antivirals is a healthcare imperative. we explored the potentials of polyoxometalates to inhibit hcv infection using newly developed hcvcc cell culture system. we found one polyoxometalate compound (named pom-12) can inhibit hcv infection at the nanomolar range while displayed lit ...201324025401
arbidol inhibits viral entry by interfering with clathrin-dependent trafficking.arbidol (arb) is a broad-spectrum antiviral displaying activity against a number of enveloped and non-enveloped viruses. it was described as a viral entry inhibitor and shown to interact at the molecular level with lipid membranes and viral fusion glycoproteins to impede viral entry and fusion. however its mechanism of action at the cellular level remains unknown. here, by using live-cell confocal imaging and the hepatitis c virus as a model virus, we show that arb affects clathrin-mediated endo ...201323981392
synthesis and broad spectrum antiviral evaluation of bis(pom) prodrugs of novel acyclic nucleosides.a series of seventeen hitherto unknown anp analogs bearing the (e)-but-2-enyl aliphatic side chain and modified heterocyclic base such as cytosine and 5-fluorocytosine, 2-pyrazinecarboxamide, 1,2,4-triazole-3-carboxamide or 4-substituted-1,2,3-triazoles were prepared in a straight approach through an olefin acyclic cross metathesis as key synthetic step. all novel compounds were evaluated for their antiviral activities against a large number of dna and rna viruses including herpes simplex virus ...201323911854
hepatic cells derived from induced pluripotent stem cells of pigtail macaques support hepatitis c virus infection.the narrow species tropism of hepatitis c virus (hcv) limits animal studies. we found that pigtail macaque (macaca nemestrina) hepatic cells derived from induced pluripotent stem cells support the entire hcv life cycle, although infection efficiency was limited by defects in the hcv cell entry process. this block was overcome by either increasing occludin expression, complementing the cells with human cd81, or infecting them with a strain of hcv with less restricted requirements for cd81. using ...201323891978
genetically modified vsv(nj) vector is capable of accommodating a large foreign gene insert and allows high level gene expression.it is desirable to develop a rna virus vector capable of accommodating large foreign genes for high level gene expression. vesicular stomatitis virus (vsv) has been used as a gene expression vector, especially indiana serotype (vsv(ind)), but less with new jersey serotype (vsv(nj)). here, we report constructions of genetically modified rvsv(nj) vector carrying various lengths of human hepatitis c virus (hcv) non-structural (ns) protein genes, level of inserted gene expression and characterizatio ...201323207069
selective estrogen receptor modulators inhibit hepatitis c virus infection at multiple steps of the virus life cycle.we screened for hepatitis c virus (hcv) inhibitors using the jfh-1 viral culture system and found that selective estrogen receptor modulators (serms), such as tamoxifen, clomifene, raloxifene, and other estrogen receptor α (erα) antagonists, inhibited hcv infection. treatment with serms for the first 2 h and treatment 2-24 h after viral inoculation reduced the production of hcv rna. treating persistently jfh-1 infected cells with serms resulted in a preferential inhibition of extracellular hcv r ...201323103222
botany, phytochemistry, pharmacology, and potential application of polygonum cuspidatum sieb.et zucc.: a review.polygonum cuspidatum sieb. et zucc. (polygonum cuspidatum), also known as reynoutria japonica houtt and huzhang in china, is a traditional and popular chinese medicinal herb. polygonum cuspidatum with a wide spectrum of pharmacological effects has been used for treatment of inflammation, favus, jaundice, scald, and hyperlipemia, etc.201323707210
dioscin's antiviral effect in vitro.dioscin is chemical compound obtained from an extract from a medical plant, air potato that is a yam species. its potential antiviral properties were analyzed in this study. in this study, dioscin's antiviral effects were tested against several viruses including adenovirus, vesicular stomatitis virus (vsv) and hepatitis b virus (hbv). by time-of-addition assay, dioscin not only blocked the initial stage of adenovirus infection, but also affected the host cell's response for viral infection. in a ...201323238077
vaccination with recombinant rna replicon particles protects chickens from h5n1 highly pathogenic avian influenza virus.highly pathogenic avian influenza viruses (hpaiv) of subtype h5n1 not only cause a devastating disease in domestic chickens and turkeys but also pose a continuous threat to public health. in some countries, h5n1 viruses continue to circulate and evolve into new clades and subclades. the rapid evolution of these viruses represents a problem for virus diagnosis and control. in this work, recombinant vesicular stomatitis virus (vsv) vectors expressing ha of subtype h5 were generated. to comply with ...201323762463
biochemical and structural studies of the oligomerization domain of the nipah virus phosphoprotein: evidence for an elongated coiled-coil homotrimer.nipah virus (niv) is a recently emerged severe human pathogen that belongs to the henipavirus genus within the paramyxoviridae family. the niv genome is encapsidated by the nucleoprotein (n) within a helical nucleocapsid that is the substrate used by the polymerase for transcription and replication. the polymerase is recruited onto the nucleocapsid via its cofactor, the phosphoprotein (p). the niv p protein has a modular organization, with alternating disordered and ordered domains. among these ...201324074578
regulation of the mir155 host gene in physiological and pathological processes.micrornas (mirnas), a family of small nonprotein-coding rnas, play a critical role in posttranscriptional gene regulation by acting as adaptors for the mirna-induced silencing complex to inhibit gene expression by targeting mrnas for translational repression and/or cleavage. mir-155-5p and mir-155-3p are processed from the b-cell integration cluster (bic) gene (now designated, mir155 host gene or mir155hg). mir-155-5p is highly expressed in both activated b- and t-cells and in monocytes/macropha ...201323246696
exhaustive proteome mining for functional mhc-i ligands.we present the development and application of a new machine-learning approach to exhaustively and reliably identify major histocompatibility complex class i (mhc-i) ligands among all 20(8) octapeptides and in genome-derived proteomes of mus musculus , influenza a h3n8, and vesicular stomatitis virus (vsv). focusing on murine h-2k(b), we identified potent octapeptides exhibiting direct mhc-i binding and stabilization on the surface of tap-deficient rma-s cells. computationally identified vsv-deri ...201323772559
extracts of medicinal herb sanguisorba officinalis inhibit the entry of human immunodeficiency virus type one.highly active antiretroviral therapy (haart) has been successful in reducing hiv-1-associated morbidity and mortality since its introduction in 1996. it, however, fails to eradicate hiv-1 infection thoroughly. the high cost of life-long haart and the emergence of drug resistance among hiv-1-infected individuals have brought renewed pressure for the discovery of novel antivirals and alternative medicines. traditional chinese medicine (tcm) is one of the mainstreams of complementary and alternativ ...201325191092
forced interaction of cell surface proteins with derlin-1 in the endoplasmic reticulum is sufficient to induce their dislocation into the cytosol for degradation.aberrantly folded proteins in the endoplasmic reticulum (er) are rapidly removed into the cytosol for degradation by the proteasome via an evolutionarily conserved process termed er-associated protein degradation (erad). erad of a subset of proteins requires derlin-1 for dislocation into the cytosol; however, the molecular function of derlin-1 remains unclear. human cytomegalovirus us11 exploits derlin-1-dependent erad to degrade major histocompatibility complex class i (mhc-i) molecules for imm ...201323206703
[vesicular stomatitis virus (vsv) as a vaccine vector for immunization against viral infections].vesicular stomatitis virus (vsv), a member of the rhabdoviridae family, is a promising candidate for potential use in construction of antiviral vaccines. in the natural environment vsv is a pathogen of wild ungulates and livestock. some of the features that make vsv an excellent platform for the development of a range of viral therapeutics includes its immunogenicity and ability to grow to high titers in cell lines approved for vaccine use. infection in humans is rare and usually asymptomatic, w ...201324379275
the interferon response to intracellular dna: why so many receptors?the detection of intracellular dna has emerged to be a key event in the innate immune response to viruses and intracellular bacteria, and during conditions of sterile inflammation and autoimmunity. one of the consequences of the detection of dna as a 'stranger' and a 'danger' signal is the production of type i interferons and pro-inflammatory cytokines. much work has been dedicated to the elucidation of the signalling cascades that activate this dna-induced gene expression programme. however, wh ...201323962476
6'-methyl-5'-homoaristeromycin: a structural variation of the anti-orthopox virus candidate 5'-homoaristeromycin.the synthesis of 6'-methyl-5'-homoaristeromycin is described from a known 6'-ethyl ester. antiviral analysis showed the (s)-6' stereoisomer retained the vaccinia activity of the parent 5'-homoaristeromycin (1) while the (r)-6' isomer was less active. both were weaker than 1 towards cowpox. the diastereomers were equally active versus epstein barr virus while (s)-6' was three times more active toward vesicular stomatitis virus than (r)-6'. the diastereomers were inactive towards numerous other vi ...201323727195
modulation of epstein-barr virus glycoprotein b (gb) fusion activity by the gb cytoplasmic tail domain.epstein-barr virus (ebv), along with other members of the herpesvirus family, requires a set of viral glycoproteins to mediate host cell attachment and entry. viral glycoprotein b (gb), a highly conserved glycoprotein within the herpesvirus family, is thought to be the viral fusogen based on structural comparison of ebv gb and herpes simplex virus (hsv) gb with the postfusion crystal structure of vesicular stomatitis virus fusion protein glycoprotein g (vsv-g). in addition, mutational studies in ...201323341550
the cationic cytokine il-26 differentially modulates virus infection in culture.interleukin-26 (il-26) belongs to the il-10 cytokine family, is produced by activated t cells, and targets epithelial target cells for signal transduction. here, we describe the il-26 effects on the infection of culture cells with recombinant vesicular stomatitis virus (vsv), human cytomegalovirus (hcmv), and herpes simplex virus type 1 (hsv-1) expressing green fluorescent protein. after pre-incubation with recombinant il-26 and at low multiplicity of infection, vsv showed strongly enhanced infe ...201323875025
htert extends the life of human fibroblasts without compromising type i interferon signaling.primary cells are often used to study viral replication and host-virus interactions as their antiviral pathways have not been altered or inactivated; however, their use is restricted by their short lifespan. conventional methods to extend the life of primary cultures typically utilize viral oncogenes. many of these oncogenes, however, perturb or inactivate cellular antiviral pathways, including the interferon (ifn) response. it has been previously shown that expression of the telomerase reverse ...201323472163
highly efficient retrograde gene transfer into motor neurons by a lentiviral vector pseudotyped with fusion glycoprotein.the development of gene therapy techniques to introduce transgenes that promote neuronal survival and protection provides effective therapeutic approaches for neurological and neurodegenerative diseases. intramuscular injection of adenoviral and adeno-associated viral vectors, as well as lentiviral vectors pseudotyped with rabies virus glycoprotein (rv-g), permits gene delivery into motor neurons in animal models for motor neuron diseases. recently, we developed a vector with highly efficient re ...201324086660
chimeric cyanovirin-mper recombinantly engineered proteins cause cell-free virolysis of hiv-1.human immunodeficiency virus (hiv) is the primary etiologic agent responsible for the aids pandemic. in this work, we used a chimeric recombinant protein strategy to test the possibility of irreversibly destroying the hiv-1 virion using an agent that simultaneously binds the env protein and viral membrane. we constructed a fusion of the lectin cyanovirin-n (cvn) and the gp41 membrane-proximal external region (mper) peptide with a variable-length (gly4ser)x linker (where x is 4 or 8) between the ...201323856780
comparison of heterologous prime-boost strategies against human immunodeficiency virus type 1 gag using negative stranded rna viruses.this study analyzed a heterologous prime-boost vaccine approach against hiv-1 using three different antigenically unrelated negative-stranded viruses (nsv) expressing hiv-1 gag as vaccine vectors: rabies virus (rabv), vesicular stomatitis virus (vsv) and newcastle disease virus (ndv). we hypothesized that this approach would result in more robust cellular immune responses than those achieved with the use of any of the vaccines alone in a homologous prime-boost regimen. to this end, we primed bal ...201323840600
novel inhibitors of severe acute respiratory syndrome coronavirus entry that act by three distinct mechanisms.severe acute respiratory syndrome (sars) is an infectious and highly contagious disease that is caused by sars coronavirus (sars-cov) and for which there are currently no approved treatments. we report the discovery and characterization of small-molecule inhibitors of sars-cov replication that block viral entry by three different mechanisms. the compounds were discovered by screening a chemical library of compounds for blocking of entry of hiv-1 pseudotyped with sars-cov surface glycoprotein s ( ...201323678171
the nrtis lamivudine, stavudine and zidovudine have reduced hiv-1 inhibitory activity in astrocytes.hiv-1 establishes infection in astrocytes and macroage-lineage cells of the central nervous system (cns). certain antiretroviral drugs (arvs) can penetrate the cns, and are therefore often used in neurologically active combined antiretroviral therapy (neuro-cart) regimens, but their relative activity in the different susceptible cns cell populations is unknown. here, we determined the hiv-1 inhibitory activity of cns-penetrating arvs in astrocytes and macrophage-lineage cells. primary human feta ...201323614033
m1 polarization of human monocyte-derived macrophages restricts pre and postintegration steps of hiv-1 replication.functional polarization of human monocyte-derived macrophages (mdms) into m1 cells leads to inhibition of r5 hiv-1 replication and viral dna synthesis in comparison to control, unpolarized cells together with cd4 downregulation from the cell surface and upregulation of ccr5-binding chemokine secretion. we here investigated whether a postentry restriction of virus replication is also induced by m1 polarization of mdm.201323612004
viral attachment induces rapid recruitment of an innate immune sensor (trim5α) to the plasma membrane.trim5α (tripartite motif 5α) acts as a pattern recognition receptor specific for the retrovirus capsid lattice and blocks infection by hiv-1 immediately after entry. however, the precise mechanisms underlying this rapid recognition of viral components remain elusive. here, we analyzed the influence of viral exposure on trim5α. total internal reflection fluorescence microscopy and lipid flotation assays revealed rapid recruitment of a trim5α subpopulation to the plasma membrane (pm) upon exposure ...201323548691
restriction of hiv-1 replication in primary macrophages by il-12 and il-18 through the upregulation of samhd1.monocyte-derived macrophages (mdm) can polarize into different subsets depending on the environment and the activation signal to which they are submitted. differentiation into macrophages allows hiv-1 strains to infect cells of the monocytic lineage. in this study, we show that culture of monocytes with a combination of il-12 and il-18 led to macrophage differentiation that was resistant to hiv-1 infection. in contrast, m-csf-derived mdm were readily infected by hiv-1. when monocytes were differ ...201323526823
patient monitoring and follow-up in lentiviral clinical trials.lentiviral vectors are being used with increasing frequency in human clinical trials. we were the first to use lentiviral vectors in clinical trials in 2003. our lentiviral vector encoded a long rna antisense sequence to the hiv-1 envelope and was used in an ex vivo autologous setting to provide viral load control in hiv-1 positive subjects failing anti-hiv therapy. a total of 65 subjects have been treated in phase 1 and phase 2 trials in six institutions.201323322669
virion stiffness regulates immature hiv-1 entry.human immunodeficiency virus type 1 (hiv-1) undergoes a protease-mediated maturation process that is required for its infectivity. little is known about how the physical properties of viral particles change during maturation and how these changes affect the viral lifecycle. using atomic force microscopy (afm), we previously discovered that hiv undergoes a "stiffness switch", a dramatic reduction in particle stiffness during maturation that is mediated by the viral envelope (env) protein.201323305456
poly(adp-ribose) polymerase 1 promotes transcriptional repression of integrated retroviruses.poly(adp-ribose) polymerase 1 (parp-1) is a cellular enzyme with a fundamental role in dna repair and the regulation of chromatin structure, processes involved in the cellular response to retroviral dna integration. however, the function of parp-1 in retroviral dna integration is controversial, probably due to the functional redundancy of the parp family in mammalian cells. we evaluated the function of parp-1 in retroviral infection using the chicken b lymphoblastoid cell line dt40. these cells ...201323255787
venezuelan equine encephalitis virus glycoprotein pseudotyping confers neurotropism to lentiviral vectors.we have produced high-titre hiv-1 green fluorescent protein-expressing lentiviral (lv) vectors pseudotyped with strain 3908 venezuelan equine encephalitis virus glycoprotein (veev-g) and used them to study transduction of: (1) rat embryonic motor neuron (mn) and striatal neuron primary cultures, (2) differentiated mn cell line nsc-34 and (3) adult rat striatum. in primary neuronal cultures, transduction with veev-g-pseudotyped lv was more efficient and more neuronal than with vesicular stomatiti ...201323171919
rapid detection of orf virus by loop-mediated isothermal amplification based on the dna polymerase gene.at present, there are no effective antiviral treatments available for contagious ecthyma, and rapid diagnosis is therefore critical for effective control of the disease. recently, the invention of a novel lamp technique that can rapidly amplify nucleic acids with high specificity and sensitivity under isothermal conditions has overcome some of the deficiencies of nucleic acid-based diagnostic tests and has made on-site diagnosis possible. to establish a flexible loop-mediated isothermal amplific ...201323183830
trim protein-mediated regulation of inflammatory and innate immune signaling and its association with antiretroviral activity.members of the tripartite interaction motif (trim) family of e3 ligases are emerging as critical regulators of innate immunity. to identify new regulators, we carried out a screen of 43 human trim proteins for the ability to activate nf-κb, ap-1, and interferon, hallmarks of many innate immune signaling pathways. we identified 16 trim proteins that induced nf-κb and/or ap-1. we found that one of these, trim62, functions in the trif branch of the tlr4 signaling pathway. knockdown of trim62 in pri ...201323077300
diverging role for coronin 1 in antiviral cd4+ and cd8+ t cell responses.coronin 1 is a member of the evolutionary conserved wd repeat protein family and is highly expressed in hematopoietic cells. coronin 1 is essential for ca(2+) mobilization upon t cell receptor (tcr) stimulation providing a pro-survival signal for naïve peripheral t cells. both in mouse and in human, coronin 1 deficiency is associated with severe t cell lymphopenia. in this work, we have analyzed antiviral t cell-mediated immunity in the presence and absence of coronin 1 in vivo after infection w ...201323933558
interleukin-21 is a critical cytokine for the generation of virus-specific long-lived plasma cells.long-lived plasma cells that reside in the bone marrow constitutively produce antibody in the absence of antigen and are the cellular basis of durable humoral immunity. the generation of these long-lived plasma cells depends upon a series of highly orchestrated interactions between antigen-specific cd4 t cells and b cells and the formation of germinal centers (gcs). in this study, we have examined the role of the cytokine interleukin-21 (il-21) in regulating humoral immunity during acute viral i ...201323637417
negative regulation of interferon-induced transmembrane protein 3 by set7-mediated lysine monomethylation.although lysine methylation is classically known to regulate histone function, its role in modulating antiviral restriction factor activity remains uncharacterized. interferon-induced transmembrane protein 3 (ifitm3) was found monomethylated on its lysine 88 residue (ifitm3-k88me1) to reduce its antiviral activity, mediated by the lysine methyltransferase set7. vesicular stomatitis virus and influenza a virus infection increased ifitm3-k88me1 levels by promoting the interaction between ifitm3 an ...201324129573
a small molecule multi-kinase inhibitor reduces influenza a virus replication by restricting viral rna synthesis.currently available drugs against influenza virus target the viral neuraminidase or the m2 ion channel. the emergence of viral strains resistant to these drugs has been widely described; therefore, there is an urgent need for novel antiviral drugs. targeting of host factors required for viral replication is an attractive option for circumventing the problem of drug resistance. several rnai screens have demonstrated that host kinases are required for the replication of influenza virus. to determi ...201323891991
nuclear imprisonment: viral strategies to arrest host mrna nuclear export.viruses possess many strategies to impair host cellular responses to infection. nuclear export of host messenger rnas (mrna) that encode antiviral factors is critical for antiviral protein production and control of viral infections. several viruses have evolved sophisticated strategies to inhibit nuclear export of host mrnas, including targeting mrna export factors and nucleoporins to compromise their roles in nucleo-cytoplasmic trafficking of cellular mrna. here, we present a review of research ...201323872491
a potential new pathway for pd-l1 costimulation of the cd8-t cell response to listeria monocytogenes infection.programmed death ligand-1 (pd-l1) is an important negative regulator of t cell immune responses via interactions with pd-1 and cd80. however, pd-l1 can also act as a positive costimulator, but the relevant counterreceptor is not known. we analyzed the role of pd-l1 in cd8-t cell responses to infection with listeria monocytogenes (lm) or vesicular stomatitis virus (vsv). pd-l1 blockade impaired antigen-specific cd8 effector t cell expansion in response to lm, but not to vsv infection, particularl ...201323409193
efficacy of dna vaccines forming e7 recombinant retroviral virus-like particles for the treatment of human papillomavirus-induced cancers.human papillomavirus (hpv) is involved in the development of anogenital tumors and also in the development of oropharyngeal head and neck carcinomas, where hpv-16, expressing the e6 and e7 oncoproteins, is the most frequent serotype. although vaccines encoding l1 and l2 capsid hpv proteins are efficient for the prevention of hpv infection, they are inadequate for treating established tumors. hence, development of innovative vaccine therapies targeting e6/e7 is important for controlling hpv-induc ...201323521528
transgenic chickens expressing human urokinase-type plasminogen activator.urokinase-type plasminogen activator is a serine protease that is clinically used in humans for the treatment of thrombolytic disorders and vascular diseases such as acute ischemic stroke and acute peripheral arterial occlusion. this study explored the feasibility of using chickens as a bioreactor for producing human urokinase-type plasminogen activator (hupa). recombinant hupa gene, under the control of a ubiquitous rous sarcoma virus promoter, was injected into the subgerminal cavity of freshl ...201323960123
single injection recombinant vesicular stomatitis virus vaccines protect ferrets against lethal nipah virus disease.nipah virus (niv) is a highly pathogenic zoonotic agent in the family paramyxoviridae that is maintained in nature by bats. outbreaks have occurred in malaysia, singapore, india, and bangladesh and have been associated with 40 to 75% case fatality rates. there are currently no vaccines or postexposure treatments licensed for combating human niv infection.201324330654
the differential antiviral activities of chicken interferon α (chifn-α) and chifn-β are related to distinct interferon-stimulated gene expression.chicken interferon α (chifn-α) and chifn-β are type i ifns that are important antiviral cytokines in the innate immune system. in the present study, we identified the virus-induced expression of chifn-α and chifn-β in chicken fibroblast df-1 cells and systematically evaluated the antiviral activities of recombinant chifn-α and chifn-β by cytopathic-effect (cpe) inhibition assays. we found that chifn-α exhibited stronger antiviral activity than chifn-β in terms of inhibiting the replication of ve ...201323527158
the potential of recombinant vesicular stomatitis virus-mediated virotherapy against metastatic colon cancer.colorectal cancer (crc) is the fourth most frequently diagnosed cancer and the second leading cause of cancer-related mortality in the united states. the liver and lung are the most common sites of distant metastasis of crc. the approval of newer chemotherapeutic agents such as oxaliplatin, irinotecan, bevacizumab, cetuximab and panitumumab has significantly improved survival, yet the majority of patients still succumb to the disease in less than 2 years. novel therapeutic agents that can provid ...201323232984
competitive virus assay method for titration of noncytopathogenic bovine viral diarrhea viruses (end⁺ and end⁻ viruses).a new, reliable and secure virus assay method, named the competitive virus assay (cva) method, has been established for the titration of bovine viral diarrhea viruses (bvdvs) that either show the exaltation of newcastle disease virus (end) phenomenon or heterologous interference phenomenon (but not the end phenomenon). this method is based on the principle of (1) homologous interference between bvdvs, by using bvdv rk13/e(-) or bvdv rk13/e(+) strains as competitor virus, and (2) end phenomenon a ...201323219806
characterization of a third generation lentiviral vector pseudotyped with nipah virus envelope proteins for endothelial cell transduction.lentiviruses are becoming progressively more popular as gene therapy vectors due to their ability to integrate into quiescent cells and recent clinical trial successes. directing these vectors to specific cell types and limiting off-target transduction in vivo remains a challenge. replacing the viral envelope proteins responsible for cellular binding, or pseudotyping, remains a common method to improve lentiviral targeting. here, we describe the development of a high titer, third generation lent ...201323698741
detection of receptor-induced glycoprotein conformational changes on enveloped virions by using confocal micro-raman spectroscopy.conformational changes in the glycoproteins of enveloped viruses are critical for membrane fusion, which enables viral entry into cells and the pathological cell-cell fusion (syncytia) associated with some viral infections. however, technological capabilities for identifying viral glycoproteins and their conformational changes on actual enveloped virus surfaces are generally scarce, challenging, and time-consuming. our model, nipah virus (niv), is a syncytium-forming biosafety level 4 pathogen w ...201323283947
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