Publications

TitleAbstractYear
Filter
PMID(sorted ascending)
Filter
the d10 decapping enzyme of vaccinia virus contributes to decay of cellular and viral mrnas and to virulence in mice.posttranscriptional mechanisms are important for regulation of cellular and viral gene expression. the presence of the 5' cap structure m(7)g(5')ppp(5')nm is a general feature of mrnas that provides protection from exoribonuclease digestion and enhances translation. vaccinia virus and other poxviruses encode enzymes for both cap synthesis and decapping. decapping is mediated by two related enzymes, d9 and d10, which are synthesized before and after viral dna replication, respectively. the timing ...201424155373
resistance to infection, early and persistent suppression of simian immunodeficiency virus sivmac251 viremia, and significant reduction of tissue viral burden after mucosal vaccination in female rhesus macaques.the efficacy of oral, intestinal, nasal, and vaginal vaccinations with dna simian immunodeficiency virus (siv)/interleukin-2 (il-2)/il-15, siv gag/pol/env recombinant modified vaccinia virus ankara (rmva), and at-2 sivmac239 inactivated particles was compared in rhesus macaques after low-dose vaginal challenge with sivmac251. intestinal immunization provided better protection from infection, as a significantly greater median number of challenges was necessary in this group than in the others. or ...201424155376
generation of a complete single-gene knockout bacterial artificial chromosome library of cowpox virus and identification of its essential genes.cowpox virus (cpxv) belongs to the genus orthopoxvirus in the poxviridae family. it infects a broad range of vertebrates and can cause zoonotic infections. cpxv has the largest genome among the orthopoxviruses and is therefore considered to have the most complete set of genes of all members of the genus. since cpxv has also become a model for studying poxvirus genetics and pathogenesis, we created and characterized a complete set of single gene knockout bacterial artificial chromosome (bac) clon ...201424155400
group 1 vaccinia virus zoonotic outbreak in maranhao state, brazil.in brazil, several exanthematic autochthone vaccinia virus (vacv) outbreaks affecting dairy cattle and rural workers have been reported since 1999. although outbreaks had been first described in the brazilian southeast, vacv outbreaks were notified in all brazilian regions in < 10 years. however, in this context, vacv outbreaks had not been described in some brazilian states, likely because of a lack of notification, or yet unknown epidemiological reasons. here, we describe the first vacv outbre ...201324166043
il-18 expression results in a recombinant vaccinia virus that is highly attenuated and immunogenic.interferon-γ (ifn-γ) is an attenuating factor for vaccinia virus (vacv), decreasing its virulence in vivo by more than a million fold. it is also a highly effective adjuvant when administered at the time of immunization with protein antigens. however, recombinant vacv (rvacv) vaccines expressing ifn-γ do not induce enhanced immune responses. it is possible that the ifn-γ expressed by rvacvs induces both an antiviral state and increased immunological clearance, thus resulting in decreased levels ...201424168450
a plasmid-based reverse genetics system for mammalian orthoreoviruses driven by a plasmid-encoded t7 rna polymerase.mammalian orthoreoviruses (reoviruses) have served as highly useful models for studies of virus replication and pathogenesis. the development of a plasmid-based reverse genetics system represented a major breakthrough in reovirus research. the current reverse genetics systems for reoviruses rely on the expression of t7 rna polymerase within cells transfected with reovirus gene-segment cdna plasmids. in these systems, the t7 rna polymerase is provided by using a recombinant vaccinia virus express ...201424183920
vaccinia virus glv-1h153 in combination with 131i shows increased efficiency in treating triple-negative breast cancer.we investigated the therapeutic efficacy of a replication-competent oncolytic vaccinia virus, glv-1h153, carrying human sodium iodide symporter (hnis), in combination with radioiodine in an orthotopic triple-negative breast cancer (tnbc) murine model. in vitro viral infection was confirmed by immunoblotting and radioiodine uptake assays. orthotopic xenografts (mda-mb-231 cells) received intratumoral injection of glv-1h153 or pbs. one week after viral injection, xenografts were randomized into 4 ...201424186964
cd8 t cell memory to a viral pathogen requires trans cosignaling between hvem and btla.defining the molecular interactions required to program activated cd8 t cells to survive and become memory cells may allow us to understand how to augment anti-viral immunity. hvem (herpes virus entry mediator) is a member of the tumor necrosis factor receptor (tnfr) family that interacts with ligands in the tnf family, light and lymphotoxin-α, and in the ig family, b and t lymphocyte attenuator (btla) and cd160. the ig family members initiate inhibitory signaling when engaged with hvem, but may ...201324205056
virus-encoded ectopic cd74 enhances poxvirus vaccine efficacy.vaccinia virus (vv) has been used globally as a vaccine to eradicate smallpox. widespread use of this viral vaccine has been tempered in recent years because of its immuno-evasive properties, with restrictions prohibiting vv inoculation of individuals with immune deficiencies or atopic skin diseases. vv infection is known to perturb several pathways for immune recognition including mhc class ii (mhcii) and cd1d-restricted antigen presentation. mhcii and cd1d molecules associate with a conserved ...201424205828
cascade regulation of vaccinia virus gene expression is modulated by multistage promoters.vaccinia virus contains ~200 genes classified temporally as early, intermediate or late. we analyzed 53 intermediate promoters to determine whether any have dual late promoter activity. our strategy involved (i) construction of a cell line that stably expressed the three late transcription factors, (ii) infection with a vaccinia virus mutant that expresses rna polymerase but neither intermediate nor late transcription factors, and (iii) transfection with plasmids containing a luciferase reporter ...201324210117
development and comparison of a quantitative taqman-mgb real-time pcr assay to three other methods of quantifying vaccinia virions.plaque assays are a widely used method to quantify stocks of viruses. although this method is well established for titrating viral stocks, it is time consuming and can take several days to complete. in this study, the creation and validation of a quantitative real-time pcr (qpcr) assay for enumerating virions of vaccinia virus is reported. pcr primers and a minor groove-binding probe were designed to hybridize to the dna polymerase gene (e9l) from a number of different orthopoxviruses. the numbe ...201424211297
involvement of the cellular phosphatase dusp1 in vaccinia virus infection.poxviruses encode a large variety of proteins that mimic, block or enhance host cell signaling pathways on their own benefit. it has been reported that mitogen-activated protein kinases (mapks) are specifically upregulated during vaccinia virus (vacv) infection. here, we have evaluated the role of the mapk negative regulator dual specificity phosphatase 1 (dusp1) in the infection of vacv. we demonstrated that dusp1 expression is enhanced upon infection with the replicative wr virus and with the ...201324244156
proteomic, cellular, and network analyses reveal new dusp3 interactions with nucleolar proteins in hela cells.dusp3 (or vaccinia virus phosphatase vh1-related; vhr) is a small dual-specificity phosphatase known to dephosphorylate c-jun n-terminal kinases and extracellular signal-regulated kinases. in human cervical cancer cells, dusp3 is overexpressed, localizes preferentially to the nucleus, and plays a key role in cellular proliferation and senescence triggering. other dusp3 functions are still unknown, as illustrated by recent and unpublished results from our group showing that this enzyme mediates d ...201324245651
the canarypox virus vector alvac induces distinct cytokine responses compared to the vaccinia virus-based vectors mva and nyvac in rhesus monkeys.despite the growing use of poxvirus vectors as vaccine candidates for multiple pathogens and cancers, their innate stimulatory properties remain poorly characterized. here we show that the canarypox virus-based vector alvac induced distinct systemic proinflammatory and antiviral cytokine and chemokine levels following the vaccination of rhesus monkeys compared to the vaccinia virus-based vectors mva and nyvac. these data suggest that there are substantial biological differences among leading pox ...201424257612
isg15 is counteracted by vaccinia virus e3 protein and controls the proinflammatory response against viral infection.conjugation of isg15 inhibits replication of several viruses. here, using an expression system for assaying human and mouse isg15 conjugations (isgylations), we have demonstrated that vaccinia virus e3 protein binds and antagonizes human and mouse isg15 modification. to study isgylation importance in poxvirus infection, we used a mouse model that expresses deconjugating proteases. our results indicate that isgylation restricts in vitro replication of the vaccinia virus vvδe3l mutant but unconjug ...201324257616
actin assessment in addition to specific immuno-fluorescence staining to demonstrate rickettsial growth in cell culture.rickettsiae are able to spread within infected cell mono-layers by modifying intra-cellular actin formations. the study analyzes whether a visualization of actin modifications in addition to specific immuno-fluorescence staining of rickettsiae might facilitate the proof of rickettsial growth in cell culture. cell mono-layers of vero e6 und bgm cells were infected with rickettsia honei. intra-cellular actin was fluorescence stained with tritc-(tetra-methyl-5,6-isothiocyanate)-labeled phalloidin i ...201324265939
reemergence of vaccinia virus during zoonotic outbreak, pará state, brazil.in 2010, vaccinia virus caused an outbreak of bovine vaccinia that affected dairy cattle and rural workers in pará state, brazil. genetic analyses identified the virus as distinct from bean58058 vaccinia virus (identified in 1960s) and from smallpox vaccine virus strains. these findings suggest spread of autochthonous group 1 vaccinia virus in this region.201324274374
vaccinia virus in household environment during bovine vaccinia outbreak, brazil. 201324274787
cdc42 and the rho gef intersectin-1 collaborate with nck to promote n-wasp-dependent actin polymerisation.vaccinia virus enhances its cell-to-cell spread by inducing arp2/3-dependent actin polymerisation. this process is initiated by src- and abl-mediated phosphorylation of the viral transmembrane protein a36, leading to recruitment of a signalling network consisting of grb2, nck, wip and n-wasp. nck is a potent activator of n-wasp-arp2/3-dependent actin polymerisation. however, recent observations demonstrate that an interaction between nck and n-wasp is not required for vaccinia actin tail formati ...201424284073
cd40 ligand and tdtomato-armed vaccinia virus for induction of antitumor immune response and tumor imaging.oncolytic vaccinia virus is an attractive platform for immunotherapy. oncolysis releases tumor antigens and provides co-stimulatory danger signals. however, arming the virus can improve efficacy further. cd40 ligand (cd40l, cd154) can induce apoptosis of tumor cells and it also triggers several immune mechanisms. one of these is a t-helper type 1 (th1) response that leads to activation of cytotoxic t-cells and reduction of immune suppression. therefore, we constructed an oncolytic vaccinia virus ...201424305418
transmission of vaccinia virus, possibly through sexual contact, to a woman at high risk for adverse complications.severe adverse events, including eczema vaccinatum (ev), can result after smallpox vaccination. persons at risk for ev include those with underlying dermatologic conditions, such as atopic dermatitis. we investigated a case of vaccinia infection, possibly acquired during sexual contact with a recently vaccinated military service member, in a female maryland resident with atopic dermatitis. the u.s. department of defense's vaccine healthcare centers network (vhcn) and the centers for disease cont ...201324306023
genome-wide comparison of cowpox viruses reveals a new clade related to variola virus.zoonotic infections caused by several orthopoxviruses (opv) like monkeypox virus or vaccinia virus have a significant impact on human health. in europe, the number of diagnosed infections with cowpox viruses (cpxv) is increasing in animals as well as in humans. cpxv used to be enzootic in cattle; however, such infections were not being diagnosed over the last decades. instead, individual cases of cowpox are being found in cats or exotic zoo animals that transmit the infection to humans. both ani ...201324312452
structure of the uracil complex of vaccinia virus uracil dna glycosylase.poxvirus uracil dna glycosylases are the most diverse members of the family i uracil dna glycosylases (ungs). the crystal structure of the uracil complex of vaccinia virus uracil dna glycosylase (d4) was determined at 2.03 å resolution. one uracil molecule was located in the active-site pocket in each of the 12 noncrystallographic symmetry-related d4 subunits. although the ungs of the poxviruses (including d4) feature significant differences in the characteristic motifs designated for uracil rec ...201324316823
persistent suppression of type 1 diabetes by a multicomponent vaccine containing a cholera toxin b subunit-autoantigen fusion protein and complete freund's adjuvant.data presented here demonstrate multifunctional vaccination strategies that harness vaccinia virus mediated delivery of a gene encoding an immunoenhanced diabetes autoantigen in combination with complete freund's adjuvant (cfa) that can maintain safe and durable immunologic homeostasis in nod mice. systemic coinoculation of prediabetic mice with recombinant vaccinia virus rvv-ctb::gad and undiluted or 10-fold diluted cfa demonstrated a significant decrease in hyperglycemia and pancreatic islet i ...201324319466
oncolytic vaccinia virus in combination with radiation shows synergistic antitumor efficacy in pancreatic cancer.combining oncolytic viruses with conventional therapy such as radiation is an innovative option for pancreatic cancer. we demonstrated that combination of glv-1h151 and radiation yielded a synergistic cytotoxic effect, with the greatest effect achieved in the aspc-1cell line. combination treatment significantly increased apoptosis compared with either single treatment or the control group. in mice bearing human pancreatic tumor xenografts, combination treatment resulted in significantly enhanced ...201424321381
transcutaneous yellow fever vaccination of subjects with or without atopic dermatitis.atopic dermatitis (ad) is a common inflammatory skin disease with a global prevalence ranging from 3% to 20%. patients with ad have an increased risk for complications after viral infection (eg, herpes simplex virus), and vaccination of patients with ad with live vaccinia virus is contraindicated because of a heightened risk of eczema vaccinatum, a rare but potentially lethal complication associated with smallpox vaccination.201324331381
combination of virotherapy and t-cell therapy: arming oncolytic virus with t-cell engagers.while cure rates for several cancers have significantly improved, the outcome for patients with advanced solid tumors remains grimly unchanged over the last decades. thus, there is a need for new therapies that could improve outcome for patients who fail current therapies. oncolytic vaccinia virus (vv) would be an appealing addition to the current therapies of cancers because of its ability to infect, replicate in, and lyse tumor cells, and spread to other tumor cells in successive rounds of rep ...201324333405
prime-boost vaccination with plasmid dna followed by recombinant vaccinia virus expressing bggarp induced a partial protective immunity to inhibit babesia gibsoni proliferation in dogs.a heterologous prime-boost vaccination regime with dna and recombinant vaccinia virus (rvv) vectors expressing relevant antigens has been shown to induce effective immune responses against several infectious pathogens. in this study, we describe the effectiveness of the prime-boost strategy by immunizing dogs with a recombinant plasmid followed by vaccinia virus, both of which expressed the glutamic acid-rich protein (bggarp) of babesia gibsoni. the dogs immunized with the prime-boost regime dev ...201324338330
reliefseq: a gene-wise adaptive-k nearest-neighbor feature selection tool for finding gene-gene interactions and main effects in mrna-seq gene expression data.relief-f is a nonparametric, nearest-neighbor machine learning method that has been successfully used to identify relevant variables that may interact in complex multivariate models to explain phenotypic variation. while several tools have been developed for assessing differential expression in sequence-based transcriptomics, the detection of statistical interactions between transcripts has received less attention in the area of rna-seq analysis. we describe a new extension and assessment of rel ...201324339943
characterization and structure of the vaccinia virus nf-κb antagonist a46.successful vaccinia virus (vacv) replication in the host requires expression of viral proteins that interfere with host immunity, such as antagonists of the activation of the proinflammatory transcription factor nf-κb. two such vacv proteins are a46 and a52. a46 interacts with the toll-like receptor/interleukin-1r (tir) domain of toll-like receptors and intracellular adaptors such as mal (myd88 adapter-like), tram (tir domain-containing adapter-inducing interferon-β (trif)-related adaptor molecu ...201424356965
a replicating modified vaccinia tiantan strain expressing an avian-derived influenza h5n1 hemagglutinin induce broadly neutralizing antibodies and cross-clade protective immunity in mice.to combat the possibility of a zoonotic h5n1 pandemic in a timely fashion, it is necessary to develop a vaccine that would confer protection against homologous and heterologous human h5n1 influenza viruses. using a replicating modified vaccinia virus tian tan strain (mvtt) as a vaccine vector, we constructed mvttha-qh and mvttha-ah, which expresses the h5 gene of a goose-derived qinghai strain a/bar-headed goose/qinghai/1/2005 or human-derived anhui strain a/anhui/1/2005. the immunogenicity prof ...201324358269
effects of different promoters on the virulence and immunogenicity of a hiv-1 env-expressing recombinant vaccinia vaccine.previously, we developed a vaccination regimen that involves priming with recombinant vaccinia virus lc16m8δ (rm8δ) strain followed by boosting with a sendai virus-containing vector. this protocol induced both humoral and cellular immune responses against the hiv-1 envelope protein. the current study aims to optimize this regimen by comparing the immunogenicity and safety of two rm8δ strains that express hiv-1 env under the control of a moderate promoter, p7.5, or a strong promoter, psfj1-10. m8 ...201424370703
vaccinia virus inhibits nf-κb-dependent gene expression downstream of p65 translocation.the transcription factor nuclear factor kappa light-chain enhancer of activated b cells (nf-κb) plays a critical role in host defense against viral infection by inducing the production of proinflammatory mediators and type i interferon. consequently, viruses have evolved many mechanisms to block its activation. the poxvirus vaccinia virus (vacv) encodes numerous inhibitors of nf-κb activation that target multiple points in the signaling pathway. a derivative of vacv strain copenhagen, called vv8 ...201424371075
a rev-independent gag/pol eliminates detectable psi-gag recombination in lentiviral vectors.lentiviral vectors (lvs) are being developed for clinical use in humans for applications including gene therapy and immunotherapy. a safety concern for use of lvs in humans is the generation of replication-competent lentivirus (rcl), which may arise due to recombination between the split genomes of third-generation lvs. although no rcl has been detected to date, design optimizations that minimize recombination events between split genome vectors would provide an added safety benefit that may fur ...201324380052
antimicrobial and cytotoxic activities of turbinariaconoides (j.agardh) kuetz.brown alga, turbinariaconoideswas successively extracted with n-hexane, cyclohexane, methanol and ethanol:water (1:1). the extracts were evaluated for antibacterial and antifungal activities by disc diffusion method. minimal inhibitory concentration was determined for active extracts by broth dilution method. the antiviral activity and cytotoxicity of the extracts were tested in human embryonic lung (hel) cells (herpes simplex virus-1, herpes simplex virus-2, vaccinia virus, vesicular stomatitis ...201024381606
a novel oncolytic viral therapy and imaging technique for gastric cancer using a genetically engineered vaccinia virus carrying the human sodium iodide symporter.gastric cancers have poor overall survival despite recent advancements in early detection methods, endoscopic resection techniques, and chemotherapy treatments. vaccinia viral therapy has had promising therapeutic potential for various cancers and has a great safety profile. we investigated the therapeutic efficacy of a novel genetically-engineered vaccinia virus carrying the human sodium iodide symporter (hnis) gene, glv-1 h153, on gastric cancers and its potential utility for imaging with (99m ...201424383569
giving oncolytic vaccinia virus more bite. 201424384909
antibiotic-dependent expression of early transcription factor subunits leads to stringent control of vaccinia virus replication.the use of vaccinia virus (vacv) as the vaccine against variola virus resulted in the eradication of smallpox. vacv has since been used in the development of recombinant vaccine and therapeutic vectors, but complications associated with uncontrolled viral replication have constrained its use as a live viral vector. we propose to improve the safety of vacv as a live-replicating vector by using elements of the tet operon to control the transcription of genes that are essential for viral growth. po ...201424394294
myd88-dependent immunity to a natural model of vaccinia virus infection does not involve toll-like receptor 2.although the pattern recognition receptor toll-like receptor 2 (tlr2) is typically thought to recognize bacterial components, it has been described to alter the induction of both innate and adaptive immunity to a number of viruses, including vaccinia virus (vacv). however, many pathogens that reportedly encode tlr2 agonists may actually be artifactually contaminated during preparation, possibly with cellular debris or merely with molecules that sensitize cells to be activated by authentic tlr2 a ...201424403581
genome sequence of wau86/88-1, a new variant of vaccinia virus lister strain from poland.the poxviruses warsaw agricultural university 86 (wau86) and 88-1 (wau88-1) were isolated in 1986 to 1988 from separate outbreaks in laboratory mice in poland and described as ectromelia virus isolates. the genome sequences of these poxviruses reveal that they are almost identical and represent a novel variant of the vaccinia virus lister strain.201424407630
il-10 suppresses il-17-mediated dermal inflammation and reduces the systemic burden of vaccinia virus in a mouse model of eczema vaccinatum.individuals with atopic dermatitis (ad) are susceptible to a severe, potentially fatal, systemic infection and inflammatory response following exposure to vaccinia virus (vv). il-10 acts both as an inducer of th2 responses and as a regulator of t cell activation. it has been shown to limit skin inflammation elicited by contact sensitizers. ad exacerbations have been associated with decreased il-10 function. we used il-10(-/-) mice to test the role of the cytokine in vv immunity. they exhibited l ...201324412909
susceptibility of the wild-derived inbred cast/ei mouse to infection by orthopoxviruses analyzed by live bioluminescence imaging.classical inbred mice are extensively used for virus research. however, we recently found that some wild-derived inbred mouse strains are more susceptible than classical strains to monkeypox virus. experiments described here indicated that the 50% lethal dose of vaccinia virus (vacv) and cowpox virus (cpxv) were two logs lower in wild-derived inbred cast/ei mice than classical inbred balb/c mice, whereas there was little difference in the susceptibility of the mouse strains to herpes simplex vir ...201324418545
the live vector approach-viruses.recombinant dna technology has made it possible to express foreign genes in viruses and bacteria. this has led to the idea of engineering live attenuated vaccines to express protective antigens from foreign pathogens. vaccinia virus, the smallpox vaccine, has been used to ploneer this approach. several hundred recombinants have been recorded in the literature and many of them have been shown to protect animals against challenge with the appropriate pathogen. although mixed results have been obta ...199124424925
traf2 facilitates vaccinia virus replication by promoting rapid virus entry.tumor necrosis factor receptor (tnfr)-associated factor 2 (traf2) is a pivotal intracellular mediator of signaling pathways downstream of tnfr1 and -2 with known pro- and antiviral effects. we investigated its role in the replication of the prototype poxvirus vaccinia virus (vacv). loss of traf2 expression, either through small interfering rna treatment of hela cells or through genetic knockout in murine embryonic fibroblasts (mefs), led to significant reductions in vacv growth following low-mul ...201424429366
oncolytic vaccinia virotherapy for endometrial cancer.oncolytic virotherapy is a promising modality in endometrial cancer (ec) therapy. in this study, we compared the efficacy of the copenhagen and wyeth strains of oncolytic vaccinia virus (vv) incorporating the human thyroidal sodium iodide symporter (hnis) as a reporter gene (vvnis-c and vvnis-w) in ec.201424434058
sirna screen of early poxvirus genes identifies the aaa+ atpase d5 as the virus genome-uncoating factor.poxvirus genome uncoating is a two-step process. first, cytoplasmic viral cores are activated and early viral genes are expressed. next, cores are disassembled and the genomes released. this second step depends on an early viral factor(s) that has eluded identification for over 40 years. we used a large-scale, high-throughput rnai screen directed against vaccinia virus (vacv) to identify the vacv aaa+ atpase d5 as the poxvirus uncoating factor. we show that the atpase activity of d5 is required ...201424439902
a novel role for the apoptosis inhibitor arc in suppressing tnfα-induced regulated necrosis.tnfα signaling can promote apoptosis or a regulated form of necrosis. arc (apoptosis repressor with card (caspase recruitment domain)) is an endogenous inhibitor of apoptosis that antagonizes both the extrinsic (death receptor) and intrinsic (mitochondrial/er) apoptosis pathways. we discovered that arc blocks not only apoptosis but also necrosis. tnfα-induced necrosis was abrogated by overexpression of wild-type arc but not by a card mutant that is also defective for inhibition of apoptosis. con ...201424440909
structure of human pir1, an atypical dual-specificity phosphatase.pir1 is an atypical dual-specificity phosphatase (dsp) that dephosphorylates rna with a higher specificity than phosphoproteins. here we report the atomic structure of a catalytically inactive mutant (c152s) of the human pir1 phosphatase core (pir1-core, residues 29-205), refined at 1.20 å resolution. pir1-core shares structural similarities with dsps related to vaccinia virus vh1 and with rna 5'-phosphatases such as the baculovirus rna triphosphatase and the human mrna capping enzyme. the pir1 ...201424447265
laboratory-acquired buffalopox virus infection, india. 201424447599
electron tomography and simulation of baculovirus actin comet tails support a tethered filament model of pathogen propulsion.several pathogens induce propulsive actin comet tails in cells they invade to disseminate their infection. they achieve this by recruiting factors for actin nucleation, the arp2/3 complex, and polymerization regulators from the host cytoplasm. owing to limited information on the structural organization of actin comets and in particular the spatial arrangement of filaments engaged in propulsion, the underlying mechanism of pathogen movement is currently speculative and controversial. using electr ...201424453943
mouse cmv infection delays antibody class switch upon an unrelated virus challenge.poor immune protection upon vaccination is a critical determinant of immunosenescence. latent cytomegalovirus (cmv) infection has been associated with poor antibody responses to vaccination, but a causative role for cmv in the poor immune response requires experimental evidence and thus could not be confirmed in clinical studies. to test the hypothesis that latent cmv infection causes poor antibody responses, we infected young or adult mice with mouse cmv and challenged them with vesicular stoma ...201424462805
novel insights on the progression of intermediate viral forms in the morphogenesis of vaccinia virus.morphogenesis of vaccinia virus (vacv) is a complex structural process in which the capture of all cytoplasmic stages is difficult due to the rapid transition between the different viral forms. taking advantage of two vacv mutants (m65 and m101) with defined genetic alterations, we described by transmission electron microscopy (tem) of ultrathin sections novel potential transition viral forms (ts) with reorganization of the immature virus (iv) membrane and construction of the internal core, and ...201424468494
methodology for the efficient generation of fluorescently tagged vaccinia virus proteins.tagging of viral proteins with fluorescent proteins has proven an indispensable approach to furthering our understanding of virus-host interactions. vaccinia virus (vacv), the live vaccine used in the eradication of smallpox, is particularly amenable to fluorescent live-cell microscopy owing to its large virion size and the ease with which it can be engineered at the genome level. we report here an optimized protocol for generating recombinant viruses. the minimal requirements for targeted homol ...201424473272
oncolytic vaccinia virus demonstrates antiangiogenic effects mediated by targeting of vegf.oncolytic vaccinia virus has been shown to induce a profound, rapid and tumor-specific vascular collapse in both preclinical models and clinical studies; however, a complete examination of the kinetics and levels of collapse and revascularization has not been described previously. contrast-enhanced ultrasound was used to follow tumor perfusion levels in mouse tumor models at times after vaccinia therapy. it was observed that revascularization after viral therapy was dramatically delayed and did ...201424474587
vaccinia virus requires glutamine but not glucose for efficient replication.viruses require host cell metabolism to provide the necessary energy and biosynthetic precursors for successful viral replication. vaccinia virus (vacv) is a member of the poxviridae family, and its use as a vaccine enabled the eradication of variola virus, the etiologic agent of smallpox. a global metabolic screen of vacv-infected primary human foreskin fibroblasts suggested that glutamine metabolism is altered during infection. glutamine and glucose represent the two main carbon sources for ma ...201424501408
critical role of endoplasmic reticulum aminopeptidase 1 in determining the length and sequence of peptides bound and presented by hla-b27.hla-b27 and endoplasmic reticulum aminopeptidase 1 (erap1) are the two strongest genetic factors predisposing to ankylosing spondylitis (as). a key aminopeptidase in class i major histocompatibility complex presentation, erap1 potentially contributes to the pathogenesis of as by altering hla-b27 peptide presentation. the aim of this study was to analyze the effects of erap1 on the hla-b27 peptide repertoire and peptide presentation to cytotoxic t lymphocytes (ctls).201424504800
t-bet and eomes instruct the development of two distinct natural killer cell lineages in the liver and in the bone marrow.trail(+)dx5(-)eomes(-) natural killer (nk) cells arise in the mouse fetal liver and persist in the adult liver. their relationships with trail(-)dx5(+) nk cells remain controversial. we generated a novel eomes-gfp reporter murine model to address this question. we found that eomes(-) nk cells are not precursors of classical eomes(+) nk cells but rather constitute a distinct lineage of innate lymphoid cells. eomes(-) nk cells are strictly dependent on both t-bet and il-15, similarly to nkt cells. ...201424516120
the master regulator of the cellular stress response (hsf1) is critical for orthopoxvirus infection.the genus orthopoxviridae contains a diverse group of human pathogens including monkeypox, smallpox and vaccinia. these viruses are presumed to be less dependent on host functions than other dna viruses because they have large genomes and replicate in the cytoplasm, but a detailed understanding of the host factors required by orthopoxviruses is lacking. to address this topic, we performed an unbiased, genome-wide pooled rnai screen targeting over 17,000 human genes to identify the host factors t ...201424516381
profile of natural killer cells after a previous natural vaccinia virus infection in an in vitro viral re-exposure.the present study compares the profile of nk cells in an in vitro re-exposure by vaccinia virus (vacv), in groups that have had a previous vaccination or natural infection. our data suggests that stimulation with vacv triggers a cytotoxic response by nk cells marked by an increase of ncrs: nkp30, nkp44, and nkp46 in infected (vaccinated and unvaccinated) subjects and in non-infected vaccinated patients, when compared with non-infected unvaccinated individuals. however, the degranulation and secr ...201424530576
vaccination, vaccinia virus and vaccine lymph. 195024538092
[effect of antibiotic virusin 1609 on vaccinia virus and taylor's virus]. 201424544539
boosting functional avidity of cd8+ t cells by vaccinia virus vaccination depends on intrinsic t-cell myd88 expression but not the inflammatory milieu.t-cell functional avidity is a crucial determinant for efficient pathogen clearance. although recombinant dna priming coupled with a vaccinia-vectored vaccine (vacv) boost has been widely used to mount robust cd8+ t-cell responses, how vacv boost shapes the properties of memory cd8+ t cells remains poorly defined. here, we characterize the memory cd8+ t cells boosted by vacv and demonstrate that the intrinsic expression of myd88 is critical for their high functional avidity. independent of selec ...201424554667
antitumor activity and immunogenicity of recombinant vaccinia virus expressing hpv 16 e7 protein sige7lamp is enhanced by high-level coexpression of igfbp-3.we constructed recombinant vaccinia viruses (vacvs) coexpressing the insulin-like growth factor-binding protein-3 (igfbp-3) gene and the fusion gene encoding the sige7lamp antigen. the expression of the igfbp-3 transgene was regulated either by the early h5 promoter or by the synthetic early/late (e/l) promoter. we have shown that igfbp-3 expression regulated by the h5 promoter yielded higher amount of igfbp-3 protein when compared with the e/l promoter. the immunization with p13-sige7lamp-h5-ig ...201424556712
orthopoxvirus inhibitors that are active in animal models: an update from 2008 to 2012.antiviral agents are being sought as countermeasures for the potential deliberate release of smallpox (variola) and monkeypox viruses, for the treatment of naturally acquired monkeypox virus infections, and as therapy for complications due to smallpox (live-attenuated vaccinia virus) vaccination or accidental infection after exposure to vaccinated persons. reviews of the scientific literature spanning 1950-2008 have documented the progress made in developing small-animal models of poxvirus infec ...201324563659
the recombinant vaccinia virus gene product, b18r, neutralizes interferon alpha and alleviates histopathological complications in an hiv encephalitis mouse model.interferon-alpha (ifn-α) has been identified as a neurotoxin that plays a prominent role in human immunodeficiency virus (hiv)-associated neurocognitive disorders and hiv encephalitis (hive) pathology. ifn-α is associated with cognitive dysfunction in other inflammatory diseases where ifn-α is upregulated. trials of monoclonal anti-ifn-α antibodies have been generally disappointing possibly due to high specificity to limited ifn-α subtypes and low affinity. we investigated a novel ifn-α inhibito ...201424564363
strikingly poor cd8+ t-cell immunogenicity of vaccinia virus strain mva in balb/c mice.vaccinia virus (vacv) strain mva is a highly attenuated vector for vaccines that is being explored in clinical trials. we compared the cd8(+) t-cell immunogenicity of mva with that of a virulent laboratory strain of vacv (strain wr) in balb/c mice by examining epitope-specific responses as well as estimating the total number of activated cd8(+) t cells, irrespective of specificity. we found that mva elicited total cd8(+) t-cell responses that were reduced by at least 20-fold compared with strain ...201624566805
local control of repeated-dose rectal challenges in dna/mva-vaccinated macaques protected against a first series of simian immunodeficiency virus challenges.here, we report the results of a late boost and three additional series of simian immunodeficiency virus (siv) challenges in seven dna/modified vaccinia virus ankara (mva)-vaccinated rhesus macaques who resisted a first series of rectal challenges. during 29 additional challenges delivered over 2.3 years, all animals became infected. however, 13 blips of virus in six macaques and anamnestic env-specific rectal iga responses in three of the six suggested that local control of infections was occur ...201424574408
genome scale patterns of recombination between coinfecting vaccinia viruses.recombination plays a critical role in virus evolution. it helps avoid genetic decline and creates novel phenotypes. this promotes survival, and genome sequencing suggests that recombination has facilitated the evolution of human pathogens, including orthopoxviruses such as variola virus. recombination can also be used to map genes, but although recombinant poxviruses are easily produced in culture, classical attempts to map the vaccinia virus (vacv) genome this way met with little success. we h ...201424574414
influence of sulphate on the composition and antibacterial and antiviral properties of the exopolysaccharide from porphyridium cruentum.the influence of two culture media and three different concentrations of sulphate in the medium on the growth of two strains of porphyridium cruentum and on the production, composition and viscoelastic characteristics, and antimicrobial properties of the sulphated exopolysaccharide (eps) were studied.201424582595
hiv-1 adenoviral vector vaccines expressing multi-trimeric baff and 4-1bbl enhance t cell mediated anti-viral immunity.adenoviral vectored vaccines have shown considerable promise but could be improved by molecular adjuvants. ligands in the tnf superfamily (tnfsf) are potential adjuvants for adenoviral vector (ad5) vaccines based on their central role in adaptive immunity. many tnfsf ligands require aggregation beyond the trimeric state (multi-trimerization) for optimal biological function. here we describe ad5 vaccines for hiv-1 gag antigen (ad5-gag) adjuvanted with the tnfsf ligands 4-1bbl, baff, gitrl and cd2 ...201424587225
rapid spreading and immune evasion by vaccinia virus.vaccinia virus (vacv) is the live vaccine that was used to eradicate smallpox, a feat achieved in 1977 and certified by the world health organization in 1980. since 1980, research with vacv has continued in part because of the development of techniques to genetically manipulate vacv and create live vacv strains expressing foreign genes. these recombinant vacvs can be used as live vaccines against other infectious diseases and cancers, and as a powerful tool to study virus pathogenesis, immunolog ...201424595611
differential induction of apoptosis, interferon signaling, and phagocytosis in macrophages infected with a panel of attenuated and nonattenuated poxviruses.due to the essential role macrophages play in antiviral immunity, it is important to understand the intracellular and molecular processes that occur in macrophages following infection with various strains of vaccinia virus, particularly those used as vaccine vectors. similarities as well as differences were found in macrophages infected with different poxvirus strains, particularly at the level of virus-induced apoptosis and the expression of immunomodulatory genes, as determined by microarray a ...201424599993
cell- and virus-mediated regulation of the barrier-to-autointegration factor's phosphorylation state controls its dna binding, dimerization, subcellular localization, and antipoxviral activity.barrier-to-autointegration factor (baf) is a dna binding protein with multiple cellular functions, including the ability to act as a potent defense against vaccinia virus infection. this antiviral function involves baf's ability to condense double-stranded dna and subsequently prevent viral dna replication. in recent years, it has become increasingly evident that dynamic phosphorylation involving the vaccinia virus b1 kinase and cellular enzymes is likely a key regulator of multiple baf function ...201424600006
cd4 and cd8 t cells participate in the immune memory response against vaccinia virus after a previous natural infection.the present study evaluates the immune response of memory cd4(+) and cd8(+) t cells from patients following a natural vaccinia virus (vacv) infection. a total of 42 individuals were involved in the study being: 22 previously infected individuals (vaccinated or not against smallpox) and 20 non-infected individuals (vaccinated or not). a short-term in vitro stimulation with uv-inactivated vacv of whole blood cells was performed. our study showed that previously infected individuals have a lower pe ...201324600565
analysis of sensitivity and rapid hybridization of a multiplexed microbial detection microarray.microarrays have proven to be useful in rapid detection of many viruses and bacteria. pathogen detection microarrays have been used to diagnose viral and bacterial infections in clinical samples and to evaluate the safety of biological drug materials. a multiplexed version of the lawrence livermore microbial detection array (llmda) was developed and evaluated with minimum detectable concentrations for pure unamplified dna viruses, along with mixtures of viral and bacterial dna subjected to diffe ...201424602557
crystal structure of the vaccinia virus dna polymerase holoenzyme subunit d4 in complex with the a20 n-terminal domain.vaccinia virus polymerase holoenzyme is composed of the dna polymerase e9, the uracil-dna glycosylase d4 and a20, a protein with no known enzymatic activity. the d4/a20 heterodimer is the dna polymerase co-factor whose function is essential for processive dna synthesis. genetic and biochemical data have established that residues located in the n-terminus of a20 are critical for binding to d4. however, no information regarding the residues of d4 involved in a20 binding is yet available. we expres ...201424603707
static and dynamic protein phosphorylation in the vaccinia virion.to the best of our knowledge, two phosphorylation sites have been reported previously, among 11 known vaccinia virus phosphoproteins. here, via phosphopeptide mass spectrometry, up to 189 phosphorylation sites were identified among 48 proteins in preparations of purified vaccinia mature virus (mv). 8.5% of phospho-residues were ptyr. viral phosphoproteins were found in diverse functional classes, including structural proteins, membrane proteins and rna polymerase subunits. among the nine identif ...201424606709
α4-integrins control viral meningoencephalitis through differential recruitment of t helper cell subsets.natalizumab blocks α4-integrins and is a prototypic agent for a series of anti-inflammatory drugs that impair trafficking of immune cells into the cns. however, modulation of the access of immune cells to the cns is associated with impaired immune surveillance and detrimental viral infections of the cns. here, we explored the potency of cellular immune responses within the cns to protect against viral encephalitis in mice with t cell conditional disruption of vla-4 integrin (α4β1) expression.201424606807
crystal structure of vaccinia virus mrna capping enzyme provides insights into the mechanism and evolution of the capping apparatus.vaccinia virus capping enzyme is a heterodimer of d1 (844 aa) and d12 (287 aa) polypeptides that executes all three steps in m(7)gppprna synthesis. the d1 subunit comprises an n-terminal rna triphosphatase (tpase)-guanylyltransferase (gtase) module and a c-terminal guanine-n7-methyltransferase (mtase) module. the d12 subunit binds and allosterically stimulates the mtase module. crystal structures of the complete d1⋅d12 heterodimer disclose the tpase and gtase as members of the triphosphate tunne ...201424607143
intrafamilial transmission of vaccinia virus during a bovine vaccinia outbreak in brazil: a new insight in viral transmission chain.bovine vaccinia (bv) is an emerging zoonosis caused by the vaccinia virus (vacv), genus orthopoxvirus (opv), poxviridae family. in general, human cases are related to direct contact with sick cattle but there is a lack of information about human-to-human transmission of vacv during bv outbreaks. in this study, we epidemiologically and molecularly show a case of vacv transmission between humans in são francisco de itabapoana county, rio de janeiro state. our group collected samples from the patie ...201424615135
genome segregation and packaging machinery in acanthamoeba polyphaga mimivirus is reminiscent of bacterial apparatus.genome packaging is a critical step in the virion assembly process. the putative atp-driven genome packaging motor of acanthamoeba polyphaga mimivirus (apmv) and other nucleocytoplasmic large dna viruses (ncldvs) is a distant ortholog of prokaryotic chromosome segregation motors, such as ftsk and hera, rather than other viral packaging motors, such as large terminase. intriguingly, apmv also encodes other components, i.e., three putative serine recombinases and a putative type ii topoisomerase, ...201424623441
immune control strategies for vaccinia virus-related laboratory-acquired infections.while presenting biological characteristics of vaccinia virus and laboratory-acquired infections during related research processes, this paper focuses on benefits and risks of vaccinia virus immunization in relation to laboratory-acquired infections, describes characteristics and the adaptation of vaccinia virus vaccine, analyses the role vaccinia virus immunization plays in the prevention and control of laboratory-acquired infections, and finally proposes solutions and countermeasures to furthe ...201424625408
prediction of steps in the evolution of variola virus host range.variola virus, the agent of smallpox, has a severely restricted host range (humans) but a devastatingly high mortality rate. although smallpox has been eradicated by a world health organization vaccination program, knowledge of the evolutionary processes by which human super-pathogens such as variola virus arise is important. by analyzing the evolution of variola and other closely related poxviruses at the level of single nucleotide polymorphisms we detected a hotspot of genome variation within ...201424626337
adaptive gene amplification as an intermediate step in the expansion of virus host range.the majority of recently emerging infectious diseases in humans is due to cross-species pathogen transmissions from animals. to establish a productive infection in new host species, viruses must overcome barriers to replication mediated by diverse and rapidly evolving host restriction factors such as protein kinase r (pkr). many viral antagonists of these restriction factors are species specific. for example, the rhesus cytomegalovirus pkr antagonist, rhtrs1, inhibits pkr in some african green m ...201424626510
augmented replicative capacity of the boosting antigen improves the protective efficacy of heterologous prime-boost vaccine regimens.prime-boost immunization regimens have proven efficacious at generating robust immune responses. however, whether the level of replication of the boosting antigen impacts the magnitude and protective efficacy of vaccine-elicited immune responses remains unclear. to evaluate this, we primed mice with replication-defective adenovirus vectors expressing the lymphocytic choriomeningitis virus (lcmv) glycoprotein (gp), followed by boosting with either lcmv armstrong, which is rapidly controlled, or l ...201424648461
follow-up analysis of a randomized phase iii immunotherapeutic clinical trial on melanoma.development of a melanoma-specific vaccine is of clinical necessity. therefore, a phase iii, randomized, double-blind trial was performed (june 1988-june 1991) to assess the clinical effectiveness of our vaccinia melanoma oncolysate (vmo) vaccine in stage iii melanoma patients. patient data were collected from 11 institutions, as well as from the social security death index and were analyzed from april through august 2008 for disease-free interval (dfi) and overall survival (os). the median os f ...201324649193
de novo fatty acid biosynthesis contributes significantly to establishment of a bioenergetically favorable environment for vaccinia virus infection.the poxvirus life cycle, although physically autonomous from the host nucleus, is nevertheless dependent upon cellular functions. a requirement for de novo fatty acid biosynthesis was implied by our previous demonstration that cerulenin, a fatty acid synthase inhibitor, impaired vaccinia virus production. here we show that additional inhibitors of this pathway, tofa and c75, reduce viral yield significantly, with partial rescue provided by exogenous palmitate, the pathway's end-product. palmitat ...201424651651
changes in the mitochondrial network during ectromelia virus infection of permissive l929 cells.mitochondria are extremely important organelles in the life of a cell. recent studies indicate that mitochondria also play a fundamental role in the cellular innate immune mechanisms against viral infections. moreover, mitochondria are able to alter their shape continuously through fusion and fission. these tightly regulated processes are activated or inhibited under physiological or pathological (e.g. viral infection) conditions to help restore homeostasis. however, many types of viruses, such ...201424660173
exploring mucosal immunization with a recombinant influenza virus carrying an hiv-polyepitope in mice with pre-existing immunity to influenza.hiv-1 vaccines based on recombinant vectors have been developed to elicit immune responses; however, the failure of the step hiv-1 vaccine trial has caused concern regarding the impact on vaccine efficacy of pre-existing vector seropositivity in humans. by using a mouse model of infection, we evaluated the immune responses elicited by intranasal and vaginal immunization with the recombinant influenza virus wsn/ckg carrying the pclus3-p18 peptide and a gag epitope in its hemagglutinin, and the im ...201424662706
vaccination directed against the human endogenous retrovirus-k (herv-k) gag protein slows herv-k gag expressing cell growth in a murine model system.human endogenous retroviruses (hervs) are remnants of ancestral infections and chromosomally integrated in all cells of an individual, are transmitted only vertically and are defective in viral replication. however enhanced expression of herv-k accompanied by the emergence of anti-herv-k-directed immune responses has been observed inter-alia in hiv-infected individuals and tumor patients. therefore herv-k might serve as a tumor-specific antigen or even as a constant target for the development of ...201424669861
generation of an attenuated tiantan vaccinia virus by deletion of the ribonucleotide reductase large subunit.attenuation of the virulence of vaccinia tiantan virus (vtt) underlies the strategy adopted for mass vaccination campaigns. this strategy provides advantages of safety and efficacy over traditional vaccines and is aimed at minimization of adverse health effects. in this study, a mutant form of the virus, mvtt was derived from vtt by deletion of the ribonucleotide reductase large subunit (r1) (ti4l). compared to wild-type parental (vtt) and revertant (vtt-rev) viruses, virulence of the mutant mvt ...201424677065
regional delivery of oncolytic vaccinia virus: it's time for clinical trials. 201424682649
anisotropic cell-to-cell spread of vaccinia virus on microgrooved substrate.cell-to-cell spread of virus is a comprehensive process with involvement of cellular actin cytoskeleton and substrate topography can affect the arrangement of cytoskeleton via contact guidance, yet interaction among virus, cytoskeleton and substrate topography is still unknown. to investigate the virus-cell-substrate interaction, we designed a microgrooved poly(dimethyl siloxane) (pdms) substrate for the study of vaccinia virus (vacv) cell-to-cell spread and the remodeling of cellular actin cyto ...201424685266
primary human macrophages serve as vehicles for vaccinia virus replication and dissemination.human monocytic and professional antigen-presenting cells have been reported only to exhibit abortive infections with vaccinia virus (vacv). we found that monocyte-derived macrophages (mdms), including granulocyte macrophage colony-stimulating factor (gm-csf)-polarized m1 and macrophage colony-stimulating factor (m-csf)-polarized m2, but not human ab serum-derived cells, were permissive to vacv replication. the titers of infectious virions in both cell-free supernatants and cellular lysates of i ...201424696488
alveolar macrophages are essential for protection from respiratory failure and associated morbidity following influenza virus infection.alveolar macrophages (am) are critical for defense against bacterial and fungal infections. however, a definitive role of am in viral infections remains unclear. we here report that am play a key role in survival to influenza and vaccinia virus infection by maintaining lung function and thereby protecting from asphyxiation. absence of am in gm-csf-deficient (csf2-/-) mice or selective am depletion in wild-type mice resulted in impaired gas exchange and fatal hypoxia associated with severe morbid ...201424699679
il-15 adjuvanted multivalent vaccinia-based universal influenza vaccine requires cd4+ t cells for heterosubtypic protection.current influenza vaccines are ineffective against novel viruses and the source or the strain of the next outbreak of influenza is unpredictable; therefore, establishing universal immunity by vaccination to limit the impact of influenza remains a high priority. to meet this challenge, a novel vaccine has been developed using the immunogenic live vaccinia virus as a vaccine vector, expressing multiple h5n1 viral proteins (ha, na, m1, m2, and np) together with il-15 as a molecular adjuvant. previo ...201424706798
oncolytic vaccinia virus as an adjuvant treatment to cytoreductive surgery for malignant peritoneal mesothelioma.malignant peritoneal mesothelioma (mpm) is an aggressive cancer with a dismal prognosis. oncolytic viruses are a promising new therapy for cancer because of their ability to kill tumor cells with minimal toxicity to normal tissues. this experimental study aimed to examine the potential of modified vaccinia virus (vv) to treat mpm when administered alone or as an adjuvant treatment to surgery.201424719018
structure of vaccinia virus a46, an inhibitor of tlr4 signaling pathway, shows the conformation of viper motif.vaccinia virus (vacv) encodes many proteins that interfere with the host immune system. vaccinia virus a46 protein specifically targets the bb-loop motif of tir-domain-containing proteins to disrupt receptor:adaptor (e.g., tlr4:mal and tlr4:tram) interactions of the toll-like receptor signaling. the crystal structure of a46 (75-227) determined at 2.58 å resolution showed that a46 formed a homodimer and adopted a bcl-2-like fold similar to other vacv proteins such as a52, b14, and k7. our structu ...201424723367
homosubtypic and heterosubtypic antibodies against highly pathogenic avian influenza h5n1 recombinant proteins in h5n1 survivors and non-h5n1 subjects.six recombinant vaccinia viruses containing ha, na, np, m or ns gene insert derived from a highly pathogenic avian influenza h5n1 virus, and the recombinant vaccinia virus harboring plasmid backbone as the virus control were constructed. the recombinant proteins were characterized for their expression and subcellular locations in tk(-) cells. antibodies to the five recombinant proteins were detected in all 13 sequential serum samples collected from four h5n1 survivors during four years of follow ...201424725952
[oncolytic properties of some orthopoxviruses, adenoviruses and parvoviruses in human glioma cells].currently one of the most promising approaches in development of cancer virotherapy is based on the ability of oncolytic viruses to selective infection and lysis of tumor cells.201324741936
Displaying items 11701 - 11800 of 12370