Publications
| Title | Abstract | Year Filter | PMID(sorted ascending) Filter |
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| a mouse model of atopic dermatitis. | atopic dermatitis (ad) is a chronic or chronically relapsing, pruritic inflammatory skin disease. the incidence of ad has dramatically increased for the past three decades in industrialized countries. we established a highly efficient method to induce ad-like skin lesions using repeated epicutaneous treatments with house dust mite allergen and staphylococcal enterotoxin b (seb). the dermatitis-induced mice showed increased serum ige levels that were similar to human ad patients and also treatabl ... | 2015 | 25388270 |
| a novel vaccinia virus with dual oncolytic and anti-angiogenic therapeutic effects against triple-negative breast cancer. | vascular endothelial growth factor (vegf) expression is higher in triple-negative breast cancers (tnbc) compared to other subtypes and is reported to predict incidence of distant metastases and shorter overall survival. we investigated the therapeutic impact of a vaccinia virus (vacv) glv-1h164 (derived from its parent virus glv-1h100), encoding a single-chain antibody (scab) against vegf (glaf-2) in an orthotopic tnbc murine model. glv-1h164 was tested against multiple tnbc cell lines. viral in ... | 2014 | 25391896 |
| evolution of and evolutionary relationships between extant vaccinia virus strains. | although vaccinia virus (vacv) was once used as a vaccine to eradicate smallpox on a worldwide scale, the biological origins of vacv are uncertain, as are the historical relationships between the different strains once used as smallpox vaccines. here, we sequenced additional vacv strains that either represent relatively pristine examples of old vaccines (e.g., dryvax, lister, and tashkent) or have been subjected to additional laboratory passage (e.g., ihd-w and wr). these genome sequences were c ... | 2015 | 25410873 |
| secretory iga as a vaccine carrier for delivery of hiv antigen to m cells. | hiv transmission and spread in the host are based on the survival of the virus or infected cells present in mucosal secretions, and the virus' ability to cross the epithelial barrier and access immune target cells, which leads to systemic infection. therefore, hiv-specific immunity at mucosal sites is critical for control of infection. although mucosal delivery would ensure the best onset of protective immunity, most candidate vaccines are administered through the parenteral route. remarkably, s ... | 2015 | 25412898 |
| a vaccinia virus armed with interleukin-10 is a promising therapeutic agent for treatment of murine pancreatic cancer. | vaccinia virus has strong potential as a novel therapeutic agent for treatment of pancreatic cancer. we investigated whether arming vaccinia virus with interleukin-10 (il10) could enhance the antitumor efficacy with the view that il10 might dampen the host immunity to the virus, increasing viral persistence, thus maximizing the oncolytic effect and antitumor immunity associated with vaccinia virus. | 2015 | 25416195 |
| beta-catenin signaling drives differentiation and proinflammatory function of irf8-dependent dendritic cells. | beta-catenin signaling has recently been tied to the emergence of tolerogenic dendritic cells (dcs). in this article, we demonstrate a novel role for beta-catenin in directing dc subset development through ifn regulatory factor 8 (irf8) activation. we found that splenic dc precursors express beta-catenin, and dcs from mice with cd11c-specific constitutive beta-catenin activation upregulated irf8 through targeting of the irf8 promoter, leading to in vivo expansion of irf8-dependent cd8a+, plasmac ... | 2015 | 25416805 |
| vaccinia virus induces rapid necrosis in keratinocytes by a stat3-dependent mechanism. | humans with a dominant negative mutation in stat3 are susceptible to severe skin infections, suggesting an essential role for stat3 signaling in defense against cutaneous pathogens. | 2014 | 25419841 |
| cytokine production associated with smallpox vaccine responses. | smallpox was eradicated 34 years ago due to the success of the smallpox vaccine; yet, the vaccine continues to be studied because of its importance in responding to potential biological warfare and the adverse events associated with current smallpox vaccines. interindividual variations in vaccine response are observed and are, in part, due to genetic variation. in some cases, these varying responses lead to adverse events, which occur at a relatively high rate for the smallpox vaccine compared w ... | 2014 | 25428648 |
| samd9 is an innate antiviral host factor with stress response properties that can be antagonized by poxviruses. | we show that samd9 is an innate host antiviral stress response element that participates in the formation of antiviral granules. poxviruses, myxoma virus and vaccinia virus specifically, utilize a virus-encoded host range factor(s), such as a member of the c7l superfamily, to antagonize samd9 to prevent granule formation in a eukaryotic initiation factor 2α (eif2α)-independent manner. when samd9 is stimulated due to failure of the viral antagonism during infection, the resulting antiviral granul ... | 2015 | 25428864 |
| rna polymerase iii control elements are required for trans-activation by the murine retroviral long terminal repeat sequences. | rna leukemia viruses induce t-cell lymphoblastic lymphomas or myeloid leukemias. infection of cells with moloney murine leukemia virus (m-mulv) up-regulates the expression of a number of cellular genes, including those involved in t-lymphocyte activation. previously, we demonstrated that this up-regulation occurs via the trans-activation activity of the m-mulv long terminal repeat (ltr) sequences which produce an ltr-encoded transcript. sequence analysis of the ltr revealed a potential transcrip ... | 2015 | 25446107 |
| non-coding rnas and heme oxygenase-1 in vaccinia virus infection. | small nuclear rnas (snrnas) are <200 nucleotide non-coding uridylate-rich rnas. although the functions of many snrnas remain undetermined, a population of snrnas is produced during the early phase of infection of cells by vaccinia virus. in the present study, we demonstrate a direct correlation between expression of the cytoprotective enzyme heme oxygenase-1 (ho-1), suppression of selective snrna expression, and inhibition of vaccinia virus infection of macrophages. hemin induced ho-1 expression ... | 2014 | 25450361 |
| neurotropin promotes ngf signaling through interaction of gm1 ganglioside with trk neurotrophin receptor in pc12 cells. | activation of the high-affinity nerve growth factor (ngf) receptor trk occurs through multiple processes consisted of translocation and clustering within the plasma membrane lipid rafts, dimerization and autophosphorylation. here we found that a nonprotein extract of inflamed rabbit skin inoculated with vaccinia virus (neurotropin(®)) enhanced efficiency of ngf signaling. in rat pheochromocytoma pc12 cells overexpressing trk (pctrk cells), neurotropin augmented insufficient neurite outgrowth obs ... | 2015 | 25454796 |
| rab1a promotes vaccinia virus replication by facilitating the production of intracellular enveloped virions. | vaccinia virus (vacv) is a large double-stranded dna virus with a complex cytoplasmic replication cycle that exploits numerous cellular proteins. this work characterises the role of a proviral cellular protein, the small gtpase rab1a, in vacv replication. using sirna, we identified rab1a as required for the production of extracellular enveloped virions (eevs), but not intracellular mature virions (imvs). immunofluorescence and electron microscopy further refined the role of rab1a as facilitating ... | 2015 | 25462347 |
| attenuation of monkeypox virus by deletion of genomic regions. | monkeypox virus (mpxv) is an emerging pathogen from africa that causes disease similar to smallpox. two clades with different geographic distributions and virulence have been described. here, we utilized bioinformatic tools to identify genomic regions in mpxv containing multiple virulence genes and explored their roles in pathogenicity; two selected regions were then deleted singularly or in combination. in vitro and in vivo studies indicated that these regions play a significant role in mpxv re ... | 2015 | 25462353 |
| serum indoleamine 2,3-dioxygenase activity is associated with reduced immunogenicity following vaccination with mva85a. | there is an urgent need for improved vaccines to protect against tuberculosis. the currently available vaccine bacille calmette-guerin (bcg) has varying immunogenicity and efficacy across different populations for reasons not clearly understood. mva85a is a modified vaccinia virus expressing antigen 85a from mycobacterium tuberculosis which has been in clinical development since 2002 as a candidate vaccine to boost bcg-induced protection. a recent efficacy trial in south african infants failed t ... | 2014 | 25466778 |
| structure-function analysis of vaccinia virus h7 protein reveals a novel phosphoinositide binding fold essential for poxvirus replication. | phosphoinositides and phosphoinositide binding proteins play a critical role in membrane and protein trafficking in eukaryotes. their critical role in replication of cytoplasmic viruses has just begun to be understood. poxviruses, a family of large cytoplasmic dna viruses, rely on the intracellular membranes to develop their envelope, and poxvirus morphogenesis requires enzymes from the cellular phosphoinositide metabolic pathway. however, the role of phosphoinositides in poxvirus replication re ... | 2015 | 25473060 |
| murine anti-vaccinia virus d8 antibodies target different epitopes and differ in their ability to block d8 binding to cs-e. | the imv envelope protein d8 is an adhesion molecule and a major immunodominant antigen of vaccinia virus (vacv). here we identified the optimal d8 ligand to be chondroitin sulfate e (cs-e). cs-e is characterized by a disaccharide moiety with two sulfated hydroxyl groups at positions 4' and 6' of galnac. to study the role of antibodies in preventing d8 adhesion to cs-e, we have used a panel of murine monoclonal antibodies, and tested their ability to compete with cs-e for d8 binding. among four a ... | 2014 | 25474621 |
| antigen profiling analysis of vaccinia virus injected canine tumors: oncolytic virus efficiency predicted by boolean models. | virotherapy on the basis of oncolytic vaccinia virus (vacv) strains is a novel approach for cancer therapy. in this study we describe for the first time the use of dynamic boolean modeling for tumor growth prediction of vaccinia virus glv-1h68-injected canine tumors including canine mammary adenoma (zmth3), canine mammary carcinoma (mth52c), canine prostate carcinoma (ct1258), and canine soft tissue sarcoma (stsa-1). additionally, the stsa-1 xenografted mice were injected with either livp 1.1.1 ... | 2017 | 25482233 |
| a role for the small gtpase rac1 in vaccinia actin-based motility. | vaccinia virus dissemination relies on the recruitment of the nucleation promoting factor n-wasp underneath cell-associated extracellular virus (cevs) and subsequent recruitment and activation of the arp2/3 complex, a major actin nucleator of the host cell. we have recently discovered that, in addition to the n-wasp/arp2/3 pathway, vaccinia actin-based motility also relies on the small gtpase rac1 and its downstream effector the formin-type actin nucleator fhod1. here we discuss the potential si ... | 2014 | 25483216 |
| tailored immunity by skin antigen-presenting cells. | skin vaccination aims at targeting epidermal and dermal antigen-presenting cells (apcs), indeed many subsets of different origin endowed with various functions populate the skin. the idea that the skin could represent a particularly potent site to induce adaptive and protective immune response emerged after the success of vaccinia virus vaccination by skin scarification. recent advances have shown that multiple subsets of apcs coexist in the skin and participate in immunity to infectious disease ... | 2015 | 25483512 |
| fine structure of the vaccinia virion determined by controlled degradation and immunolocalization. | the vaccinia virion is a membraned, slightly flattened, barrel-shaped particle, with a complex internal structure featuring a biconcave core flanked by lateral bodies. although the architecture of the purified mature virion has been intensely characterized by electron microscopy, the distribution of the proteins within the virion has been examined primarily using biochemical procedures. thus, it has been shown that non-ionic and ionic detergents combined or not with a sulfhydryl reagent can be u ... | 2015 | 25486587 |
| immune therapy for human papillomaviruses-related cancers. | human papillomaviruses (hpvs) are a large family of double strand dna viruses comprising more than 180 types. infection with hpv is very common and it is associated with benign and malignant proliferation of skin and squamous mucosae. many hpvs, considered low-risk such as hpv 6 and 11, produce warts; while high-risk viruses, such as hpvs 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, and 58, induce tumors. about 5% of all cancers in men and women are associated with hpv infection. because there are no ... | 2014 | 25493236 |
| programmed necrosis in the cross talk of cell death and inflammation. | cell proliferation and cell death are integral elements in maintaining homeostatic balance in metazoans. disease pathologies ensue when these processes are disturbed. a plethora of evidence indicates that malfunction of cell death can lead to inflammation, autoimmunity, or immunodeficiency. programmed necrosis or necroptosis is a form of nonapoptotic cell death driven by the receptor interacting protein kinase 3 (ripk3) and its substrate, mixed lineage kinase domain-like (mlkl). ripk3 partners w ... | 2015 | 25493335 |
| a polymeric conjugate foreignizing tumor cells for targeted immunotherapy in vivo. | antigen-specific cd8(+) cytotoxic t lymphocytes (ctls) are key elements of immunological rejection in transplantation as well as cancer immunotherapy. most tumors, however, are not immunologically rejected because they have self antigens, which are not recognized as the foreigner by ctls. in this study, we hypothesized that "foreignizing" tumor cells by delivering non-self foreign antigens into the tumors would result in rejection by foreign antigen-reactive ctls. as the model system to foreigni ... | 2015 | 25499555 |
| presence of neutralizing antibodies to orthopoxvirus in capybaras (hydrochoerus hydrochaeris) in brazil. | cantagalo virus is a strain of vaccinia virus (genus orthopoxvirus) and the etiological agent of an important vesicopustular disease that affects dairy cows and milkers in brazil. the reservoirs involved in the maintenance of this virus in nature are unknown. in the present work, the detection of neutralizing antibodies to orthopoxvirus in capybaras collected in são paulo state is reported. capybaras are the largest rodent species native to south america and have already been reported as putativ ... | 2014 | 25500667 |
| mcl1 enhances the survival of cd8+ memory t cells after viral infection. | viral infection results in the generation of massive numbers of activated effector cd8(+) t cells that recognize viral components. most of these are short-lived effector t cells (slecs) that die after clearance of the virus. however, a small proportion of this population survives and forms antigen-specific memory precursor effector cells (mpecs), which ultimately develop into memory cells. these can participate in a recall response upon reexposure to antigen even at protracted times postinfectio ... | 2015 | 25505074 |
| [apoptin enhances the oncolytic activity of vaccinia virus]. | chicken anemia virus gene encoding apoptin, a selective killer of cancer cells was synthesized and inserted into vaccinia virus (strain l-ivp) genome. the insertion has replaced major part of the viral c11r gene encoding viral growth factor (vgf), which is important for the virulence. the recombinant virus vvdgf-apos24/2 was obtained through the transient dominant selection technique with the use of puromycin resistance gene as the selective marker. the expression apoptin gene from a synthetic e ... | 2014 | 25509357 |
| the escherichia coli effector espj blocks src kinase activity via amidation and adp ribosylation. | the hallmark of enteropathogenic escherichia coli (epec) infection is the formation of actin-rich pedestal-like structures, which are generated following phosphorylation of the bacterial effector tir by cellular src and abl family tyrosine kinases. this leads to recruitment of the nck-wip-n-wasp complex that triggers arp2/3-dependent actin polymerization in the host cell. the same phosphorylation-mediated signalling network is also assembled downstream of the vaccinia virus protein a36 and the p ... | 2014 | 25523213 |
| phase 1 study of intratumoral pexa-vec (jx-594), an oncolytic and immunotherapeutic vaccinia virus, in pediatric cancer patients. | pexa-vec (pexastimogene devacirepvec, jx-594) is an oncolytic and immunotherapeutic vaccinia virus designed to destroy cancer cells through viral lysis and induction of granulocyte-macrophage colony-stimulating factor (gm-csf)-driven tumor-specific immunity. pexa-vec has undergone phase 1 and 2 testing alone and in combination with other therapies in adult patients, via both intratumoral and intravenous administration routes. we sought to determine the safety of intratumoral administration in pe ... | 2015 | 25531693 |
| cd4(+) t-cell dependence of primary cd8(+) t-cell response against vaccinia virus depends upon route of infection and viral dose. | cd4(+) t-cell help (cd4 help) plays a pivotal role in cd8(+) t-cell responses against viral infections. however, the role in primary cd8(+) t-cell responses remains controversial. we evaluated the effects of infection route and viral dose on primary cd8(+) t-cell responses to vaccinia virus (vacv) in mhc class ii(-/-) mice. cd4 help deficiency diminished the generation of vacv-specific cd8(+) t cells after intraperitoneal (i.p.) but not after intranasal (i.n.) infection. a large viral dose could ... | 2016 | 25544501 |
| activated cd4+ccr5+ t cells in the rectum predict increased siv acquisition in sivgag/tat-vaccinated rhesus macaques. | an effective t-cell-based aids vaccine should induce strong hiv-specific cd8(+) t cells in mucosal tissues without increasing the availability of target cells for the virus. here, we evaluated five immunization strategies that include human adenovirus-5 (adhu5), chimpanzee adenovirus-6 (adc6) or -7 (adc7), vaccinia virus (vv), and dna given by electroporation (dna/ep), all expressing simian immunodeficiency virus group specific antigen/transactivator of transcription (siv(mac239gag/tat)). five g ... | 2015 | 25550504 |
| proteolytic processing of the porcine reproductive and respiratory syndrome virus replicase. | the porcine reproductive and respiratory syndrome virus (prrsv) replicase polyproteins pp1a and pp1ab are proteolytically processed by four proteases encoded in orf1a. in this study, a large set of prrsv replicase cleavage products were identified and pp1a cleavage sites were verified by using a combination of bioinformatics, proteomics, immunoprecipitation, and site-directed mutagenesis. for genotype 1 prrsv (isolate sd01-08), proteomic analysis identified h180/s181, g385/a386, and g1446/a1447 ... | 2015 | 25557977 |
| postchallenge administration of brincidofovir protects healthy and immune-deficient mice reconstituted with limited numbers of t cells from lethal challenge with ihd-j-luc vaccinia virus. | protection from lethality by postchallenge administration of brincidofovir (bcv, cmx001) was studied in normal and immune-deficient (nude, nu/nu) balb/c mice infected with vaccinia virus (vacv). whole-body bioluminescence imaging was used to record total fluxes in the nasal cavity, lungs, spleen, and liver and to enumerate pox lesions on tails of mice infected via the intranasal route with 10(5) pfu of recombinant ihd-j-luc vacv expressing luciferase. areas under the flux curve (aucs) were calcu ... | 2015 | 25589648 |
| vaccinia virus protein a49 is an unexpected member of the b-cell lymphoma (bcl)-2 protein family. | vaccinia virus (vacv) encodes several proteins that inhibit activation of the proinflammatory transcription factor nuclear factor κb (nf-κb). vacv protein a49 prevents translocation of nf-κb to the nucleus by sequestering cellular β-trcp, a protein required for the degradation of the inhibitor of κb. a49 does not share overall sequence similarity with any protein of known structure or function. we solved the crystal structure of a49 from vacv western reserve to 1.8 å resolution and showed, surpr ... | 2015 | 25605733 |
| selective inactivation of usp18 isopeptidase activity in vivo enhances isg15 conjugation and viral resistance. | protein modification by the ubiquitin-like protein isg15 is an interferon (ifn) effector system, which plays a major role in antiviral defense. isg15 modification is counteracted by the isopeptidase usp18, a major negative regulator of ifn signaling, which was also shown to exert its regulatory function in an isopeptidase-independent manner. to dissect enzymatic and nonenzymatic functions of usp18 in vivo, we generated knock-in mice (usp18(c61a/c61a)) expressing enzymatically inactive usp18. usp ... | 2015 | 25605921 |
| dermal-resident versus recruited γδ t cell response to cutaneous vaccinia virus infection. | the study of t cell immunity at barrier surfaces has largely focused on t cells bearing the αβ tcr. however, t cells that express the γδ tcr are disproportionately represented in peripheral tissues of mice and humans, suggesting they too may play an important role responding to external stimuli. in this article, we report that, in a murine model of cutaneous infection with vaccinia virus, dermal γδ t cell numbers increased 10-fold in the infected ear and resulted in a novel γδ t cell population ... | 2015 | 25609844 |
| gene therapy using therapeutic and diagnostic recombinant oncolytic vaccinia virus glv-1h153 for management of colorectal peritoneal carcinomatosis. | peritoneal carcinomatosis (pc) is a terminal progression of colorectal cancer (crc). poor response to cytoreductive operation and chemotherapy coupled with the inability to reliably track disease progression by the use of established diagnostic methods, make this a deadly disease. we examined the effectiveness of the oncolytic vaccinia virus glv-1h153 as a therapeutic and diagnostic vehicle. we believe that viral expression of the human sodium iodide transporter (hnis) provides both real-time mo ... | 2015 | 25616946 |
| pushing with actin: from cells to pathogens. | actin polymerization is harnessed by cells to generate lamellipodia for movement and by a subclass of pathogens to facilitate invasion of their infected hosts. using electron tomography (et), we have shown that lamellipodia are formed via the generation of subsets of actin filaments joined by branch junctions. image averaging produced a 2.9 nm resolution model of branch junctions in situ and revealed a close fit to the electron density map of the actin-related protein 2/3 (arp2/3)-actin complex ... | 2015 | 25619250 |
| mathematical modeling provides kinetic details of the human immune response to vaccination. | with major advances in experimental techniques to track antigen-specific immune responses many basic questions on the kinetics of virus-specific immunity in humans remain unanswered. to gain insights into kinetics of t and b cell responses in human volunteers we combined mathematical models and experimental data from recent studies employing vaccines against yellow fever and smallpox. yellow fever virus-specific cd8 t cell population expanded slowly with the average doubling time of 2 days peaki ... | 2015 | 25621280 |
| could hantavirus circulation superpose areas of highly endemic vaccinia virus outbreaks? a retrospective seroepidemiological study in state of minas gerais. | hantavirus infections have been described in several regions in brazil through seroepidemiological studies. usually, populations are associated with rural and wild environment mainly due to close contact to species of sigmodontinae rodents, considered hantavirus reservoirs. | 2015 | 25626659 |
| putative e3 ubiquitin ligase of human rotavirus inhibits nf-κb activation by using molecular mimicry to target β-trcp. | nf-κb plays a critical role in the induction and maintenance of innate and adaptive immune transcriptional programs. an associated inhibitor of κb protein (iκb) regulates nf-κb activation and contains a degron motif (dsgφxs) that undergoes phosphorylation following pathogen recognition or other proinflammatory signals. the e3 ubiquitin ligase scf(β-trcp) recognizes this phosphodegron through its β-transducin repeat-containing protein (β-trcp) subunit and induces iκb degradation, allowing nf-κb t ... | 2015 | 25626907 |
| st-246 is a key antiviral to inhibit the viral f13l phospholipase, one of the essential proteins for orthopoxvirus wrapping. | st-246 is one of the key antivirals being developed to fight orthopoxvirus (opv) infections. its exact mode of action is not completely understood, but it has been reported to interfere with the wrapping of infectious virions, for which f13l (peripheral membrane protein) and b5r (type i glycoprotein) are required. here we monitored the appearance of st-246 resistance to identify its molecular target. | 2015 | 25630650 |
| the addition of recombinant vaccinia her2/neu to oncolytic vaccinia-gmcsf given into the tumor microenvironment overcomes mdsc-mediated immune escape and systemic anergy. | effective immunotherapeutic strategies require the ability to generate a systemic antigen-specific response capable of impacting both primary and metastatic disease. we have built on our oncolytic vaccinia a granulocyte-macrophage colony-stimulating factor (gm-csf) strategy by adding recombinant tumor antigen to increase the response in the tumor microenvironment and systemically. in the present study, orthotopic growth of a syngeneic her2/neu-overexpressing mammary carcinoma in fvb/n mice (nbt1 ... | 2015 | 25633483 |
| mouse model for pre-clinical study of human cancer immunotherapy. | this unit describes protocols for developing tumors in mice, including subcutaneous growth, pulmonary metastases of b16 melanoma, and spontaneous melanoma in b-raf v600e/pten deletion transgenic mouse models. two immunization methods to prevent b16 tumor growth are described using b16.gm-csf and recombinant vaccinia virus. a therapeutic approach is also included that uses adoptive transfer of tumor antigen-specific t cells. methods including ctl induction, isolation, testing, and genetic modific ... | 2015 | 25640991 |
| filaggrin deficiency promotes the dissemination of cutaneously inoculated vaccinia virus. | eczema vaccinatum is a life-threatening complication of smallpox vaccination in patients with atopic dermatitis (ad) characterized by dissemination of vaccinia virus (vv) in the skin and internal organs. mutations in the filaggrin (flg) gene, the most common genetic risk factor for ad, confer a greater risk for eczema herpeticum in patients with ad, suggesting that it impairs the response to cutaneous viral infections. | 2015 | 25649082 |
| enhancing tumor-specific intracellular delivering efficiency of cell-penetrating peptide by fusion with a peptide targeting to egfr. | cell-penetrating peptides (cpps) are well known as intracellular delivery vectors. however, unsatisfactory delivery efficiency and poor specificity are challenging barriers to cpp applications at the clinical trial stage. here, we showed that s3, an egfr-binding domain derived from vaccinia virus growth factor, when fused to a cpp such as hbd or tat can substantially enhance its internalization efficiency and tumor selectivity. the uptake of s3-hbd (s3h) recombinant molecule by tumor cells was n ... | 2015 | 25655386 |
| virological and preclinical characterization of a dendritic cell targeting, integration-deficient lentiviral vector for cancer immunotherapy. | dendritic cells (dcs) are essential antigen-presenting cells for the initiation of cytotoxic t-cell responses and therefore attractive targets for cancer immunotherapy. we have developed an integration-deficient lentiviral vector termed id-vp02 that is designed to deliver antigen-encoding nucleic acids selectively to human dcs in vivo. id-vp02 utilizes a genetically and glycobiologically engineered sindbis virus glycoprotein to target human dcs through the c-type lectin dc-sign (cd209) and also ... | 0 | 25658613 |
| african swine fever virus infects macrophages, the natural host cells, via clathrin- and cholesterol-dependent endocytosis. | the main cellular target for african swine fever virus (asfv) is the porcine macrophage. however, existing data about the early phases of infection were previously characterized in non-leukocyte cells such as vero cells. here, we report that asfv enters the natural host cell using dynamin-dependent and clathrin-mediated endocytosis. this pathway is strongly ph-dependent during the first steps of infection in porcine macrophages. we investigated the effect of drugs inhibiting several endocytic pa ... | 2015 | 25662020 |
| genetic diversity of fusion gene (orf 117), an analogue of vaccinia virus a27l gene of capripox virus isolates. | the fusion gene (orf 117) sequences of twelve (n = 12) capripox virus isolates namely sheeppox (sppv) and goatpox (gtpv) viruses from india were demonstrated for their genetic and phylogenetic relationship among them. all the isolates were confirmed for their identity by routine pcr before targeting orf 117 gene for sequence analysis. the designed primers specifically amplified orf 117 gene as 447 bp fragment from total genomic dna extracted from all the isolates. sequence analysis revealed a si ... | 2015 | 25663144 |
| evaluation of virus inactivation by formaldehyde to enhance biosafety of diagnostic electron microscopy. | formaldehyde (fa) fixation of infectious samples is a well-established protocol in diagnostic electron microscopy of viruses. however, published experimental data that demonstrate virus inactivation by these fixation procedures are lacking. usually, fixation is performed immediately before the sample preparation for microscopy. the fixation procedure should transform viruses in a non-infectious but nonetheless structurally intact form in order to allow a proper diagnosis based on morphology. fa ... | 2015 | 25674771 |
| the role of signalling and the cytoskeleton during vaccinia virus egress. | viruses are obligate intracellular parasites that are critically dependent on their hosts to replicate and generate new progeny. to achieve this goal, viruses have evolved numerous elegant strategies to subvert and utilise the different cellular machineries and processes of their unwilling hosts. moreover, they often accomplish this feat with a surprisingly limited number of proteins. among the different systems of the cell, the cytoskeleton is often one of the first to be hijacked as it provide ... | 2015 | 25681743 |
| functional analysis of the short isoform of orf virus protein ov20.0. | orf virus (orfv) ov20.0l is an ortholog of vaccinia virus (vacv) gene e3l. the function of vacv e3 protein as a virulence factor is well studied, but ov20.0 has received less attention. here we show that like vacv e3l, ov20.0l encodes two proteins, a full-length protein and a shorter form (sh20). the shorter sh20 is an n-terminally truncated ov20.0 isoform generated when a downstream aug codon is used for initiating translation. these isoforms differed in cellular localization, with full-length ... | 2015 | 25694596 |
| host proteome correlates of vaccine-mediated enhanced disease in a mouse model of respiratory syncytial virus infection. | respiratory syncytial virus (rsv) is the leading cause of lower respiratory tract infections in infants. despite over 50 years of research, to date no safe and efficacious rsv vaccine has been licensed. many experimental vaccination strategies failed to induce balanced t-helper (th) responses and were associated with adverse effects such as hypersensitivity and immunopathology upon challenge. in this study, we explored the well-established recombinant vaccinia virus (rvv) rsv-f/rsv-g vaccination ... | 2015 | 25694607 |
| progress in clinical oncolytic virus-based therapy for hepatocellular carcinoma. | hepatocellular carcinoma (hcc) carries a dismal prognosis, with advanced disease being resistant to both radiotherapy and conventional cytotoxic drugs, whilst anti-angiogenic drugs are marginally efficacious. oncolytic viruses (ovs) offer the promise of selective cancer therapy through direct and immune-mediated mechanisms. the premise of ovs lies in their preferential genomic replication, protein expression and productive infection of malignant cells. numerous ovs are being tested in preclinica ... | 2015 | 25711964 |
| transient dominant selection for the modification and generation of recombinant infectious bronchitis coronaviruses. | we have developed a reverse genetics system for the avian coronavirus infectious bronchitis virus (ibv) in which a full-length cdna corresponding to the ibv genome is inserted into the vaccinia virus genome under the control of a t7 promoter sequence. vaccinia virus as a vector for the full-length ibv cdna has the advantage that modifications can be introduced into the ibv cdna using homologous recombination, a method frequently used to insert and delete sequences from the vaccinia virus genome. ... | 2015 | 25720477 |
| poxvirus membrane biogenesis. | poxviruses differ from most dna viruses by replicating entirely within the cytoplasm. the first discernible viral structures are crescents and spherical immature virions containing a single lipoprotein membrane bilayer with an external honeycomb lattice. because this viral membrane displays no obvious continuity with a cellular organelle, a de novo origin was suggested. nevertheless, transient connections between viral and cellular membranes could be difficult to resolve. despite the absence of ... | 2015 | 25728299 |
| ectopic expression of vaccinia virus e3 and k3 cannot rescue ectromelia virus replication in rabbit rk13 cells. | as a group, poxviruses have been shown to infect a wide variety of animal species. however, there is individual variability in the range of species able to be productively infected. in this study, we observed that ectromelia virus (ectv) does not replicate efficiently in cultured rabbit rk13 cells. conversely, vaccinia virus (vacv) replicates well in these cells. upon infection of rk13 cells, the replication cycle of ectv is abortive in nature, resulting in a greatly reduced ability to spread am ... | 2015 | 25734776 |
| nfκb activation by modified vaccinia virus as a novel strategy to enhance neutrophil migration and hiv-specific t-cell responses. | neutrophils are antigen-transporting cells that generate vaccinia virus (vacv)-specific t-cell responses, yet how vacv modulates neutrophil recruitment and its significance in the immune response are unknown. we generated an attenuated vacv strain that expresses hiv-1 clade c antigens but lacks three specific viral genes (a52r, k7r, and b15r). we found that these genes act together to inhibit the nfκb signaling pathway. triple ablation in modified virus restored nfκb function in macrophages. aft ... | 2015 | 25739961 |
| the predominant species of nonstructural protein 4b in hepatitis c virus-replicating cells is not palmitoylated. | hepatitis c virus (hcv) represents a significant global health burden. viral replication is thought to occur in close association with remodelled host cell membranes, with non-structural protein 4b (ns4b) being a key player in this process. ns4b is a poorly characterized integral membrane protein, which has been reported to be palmitoylated at its carboxy-terminal end. in order to extend this observation and to establish a functional role for ns4b palmitoylation, we sought to determine the statu ... | 2015 | 25740959 |
| mutational analysis of vaccinia virus e3 protein: the biological functions do not correlate with its biochemical capacity to bind double-stranded rna. | vaccinia e3 protein has the biochemical capacity of binding to double-stranded rna (dsrna). the best characterized biological functions of the e3 protein include its host range function, suppression of cytokine expression, and inhibition of interferon (ifn)-induced antiviral activity. currently, the role of the dsrna binding capacity in the biological functions of the e3 protein is not clear. to further understand the mechanism of the e3 protein biological functions, we performed alanine scannin ... | 2015 | 25740987 |
| efficiently editing the vaccinia virus genome by using the crispr-cas9 system. | vaccinia virus (vacv) continues to be used in immunotherapy for the prevention of infectious diseases and treatment of cancer since its use for the eradication of smallpox. however, the current method of editing the vacv genome is not efficient. here, we demonstrate that the crispr-cas9 system can be used to edit the vacv genome rapidly and efficiently. additionally, a set of 8,964 computationally designed unique guide rnas (grnas) targeting all vacv genes will be valuable for the study of vacv ... | 2015 | 25741005 |
| simultaneous quantification of viral antigen expression kinetics using data-independent (dia) mass spectrometry. | the generation of antigen-specific reagents is a significant bottleneck in the study of complex pathogens that express many hundreds to thousands of different proteins or to emerging or new strains of viruses that display potential pandemic qualities and therefore require rapid investigation. in these instances the development of antibodies for example can be prohibitively expensive to cover the full pathogen proteome, or the lead time may be unacceptably long in urgent cases where new highly pa ... | 2015 | 25755296 |
| vaccinia virus protein complex f12/e2 interacts with kinesin light chain isoform 2 to engage the kinesin-1 motor complex. | during vaccinia virus morphogenesis, intracellular mature virus (imv) particles are wrapped by a double lipid bilayer to form triple enveloped virions called intracellular enveloped virus (iev). iev are then transported to the cell surface where the outer iev membrane fuses with the cell membrane to expose a double enveloped virion outside the cell. the f12, e2 and a36 proteins are involved in transport of ievs to the cell surface. deletion of the f12l or e2l genes causes a severe inhibition of ... | 2015 | 25760349 |
| topology of endoplasmic reticulum-associated cellular and viral proteins determined with split-gfp. | the split green fluorescent protein (gfp) system was adapted for investigation of the topology of er-associated proteins. a 215-amino acid fragment of gfp (s1-10) was expressed in the cytoplasm as a free protein or fused to the n-terminus of calnexin and in the er as an intraluminal protein or fused to the c-terminus of calnexin. a 16-amino acid fragment of gfp (s11) was fused to the n- or c-terminus of the target protein. fluorescence occurred when both gfp fragments were in the same intracellu ... | 2015 | 25761760 |
| vaccinia virus protein a3 is required for the production of normal immature virions and for the encapsidation of the nucleocapsid protein l4. | maturation of the vaccinia virion is an intricate process that results in the organization of the viroplasm contained in immature virions into the lateral bodies, core wall and nucleocapsid observed in the mature particles. it is unclear how this organization takes place and studies with mutants are indispensable in understanding this process. by characterizing an inducible mutant in the a3l gene, we revealed that a3, an inner core wall protein, is important for formation of normal immature viru ... | 2015 | 25765002 |
| poxvirus decapping enzymes enhance virulence by preventing the accumulation of dsrna and the induction of innate antiviral responses. | poxvirus replication involves synthesis of double-stranded rna (dsrna), which can trigger antiviral responses by inducing phosphorylation-mediated activation of protein kinase r (pkr) and stimulating 2'5'-oligoadenylate synthetase (oas). pkr inactivates the translation initiation factor eif2α via phosphorylation, while oas induces the endonuclease rnase l to degrade rna. we show that poxvirus decapping enzymes d9 and d10, which remove caps from mrnas, inhibit these antiviral responses by prevent ... | 2015 | 25766293 |
| cellular 5'-3' mrna exonuclease xrn1 controls double-stranded rna accumulation and anti-viral responses. | by accelerating global mrna decay, many viruses impair host protein synthesis, limiting host defenses and stimulating virus mrna translation. vaccinia virus (vacv) encodes two decapping enzymes (d9, d10) that remove protective 5' caps on mrnas, presumably generating substrates for degradation by the host exonuclease xrn1. surprisingly, we find vacv infection of xrn1-depleted cells inhibits protein synthesis, compromising virus growth. these effects are aggravated by d9 deficiency and dependent u ... | 2015 | 25766294 |
| variola virus f1l is a bcl-2-like protein that unlike its vaccinia virus counterpart inhibits apoptosis independent of bim. | subversion of host cell apoptosis is an important survival strategy for viruses to ensure their own proliferation and survival. certain viruses express proteins homologous in sequence, structure and function to mammalian pro-survival b-cell lymphoma 2 (bcl-2) proteins, which prevent rapid clearance of infected host cells. in vaccinia virus (vv), the virulence factor f1l was shown to be a potent inhibitor of apoptosis that functions primarily be engaging pro-apoptotic bim. variola virus (var), th ... | 2015 | 25766319 |
| cxcr3 chemokine receptor enables local cd8(+) t cell migration for the destruction of virus-infected cells. | cd8(+) t cells play a critical role in limiting peripheral virus replication, yet how they locate virus-infected cells within tissues is unknown. here, we have examined the environmental signals that cd8(+) t cells use to localize and eliminate virus-infected skin cells. epicutaneous vaccinia virus (vv) infection, mimicking human smallpox vaccination, greatly increased expression of the cxcr3 chemokine receptor ligands cxcl9 and cxcl10 in vv-infected skin. despite normal t cell numbers in the sk ... | 2015 | 25769612 |
| from lesions to viral clones: biological and molecular diversity amongst autochthonous brazilian vaccinia virus. | vaccinia virus (vacv) has had an important role for humanity because of its use during the smallpox eradication campaign. vacv is the etiologic agent of the bovine vaccinia (bv), an emerging zoonosis that has been associated with economic, social, veterinary and public health problems, mainly in brazil and india. despite the current and historical vacv importance, there is little information about its circulation, prevalence, origins and maintenance in the environment, natural reservoirs and div ... | 2015 | 25785515 |
| infected cells call their killers to the scene of the crime. | effector cd8(+) t cells scan tissues to locate and kill infected host cells. in this issue of immunity, hickman et al. (2015) show that the exploration is not random: infected monocytes attract their assassins by secreting chemokines, which accelerates clearance of epicutaneous vaccinia virus infection. | 2015 | 25786170 |
| immunogenicity and virulence of attenuated vaccinia virus tian tan encoding hiv-1 muti-epitope genes, p24 and cholera toxin b subunit in mice. | no effective prophylactic or therapeutic vaccine against hiv-1 in humans is currently available. this study analyzes the immunogenicity and safety of a recombinant attenuated vaccinia virus. a chimeric gene of hiv-1 multi-epitope genes containing cpg odn and cholera toxin b subunit (ctb) was inserted into chinese vaccinia virus tian tan strain (vtt) mutant strain. the recombinant virus rddvtt(-ccmp24) was assessed for immunogenicity and safety in mice. results showed that the protein ccmp24 was ... | 2015 | 25796990 |
| incomplete but infectious vaccinia virions are produced in the absence of oncolysis in feline sccf1 cells. | vaccinia virus is a large, enveloped virus of the poxvirus family. it has broad tropism and typically virus replication culminates in accumulation and lytic release of intracellular mature virus (imv), the most abundant form of infectious virus, as well as release by budding of extracellular enveloped virus (eev). vaccinia viruses have been modified to replicate selectively in cancer cells and clinically tested as oncolytic agents. during preclinical screening of relevant cancer targets for a re ... | 2015 | 25799430 |
| one-step duplex polymerase chain reaction for the detection of swinepox and vaccinia viruses in skin lesions of swine with poxvirus-related disease. | infection of pigs with swinepox virus (swpv) was reported in brazil in 2011. swpv causes a systemic pustular disease in pigs and the symptoms are clinically indistinguishable from those caused by vaccinia virus (vacv) infection. pigs infected with vacv have been reported in various countries; however, vacv is endemic in brazil, india and other countries, where it affects mainly dairy cows, dairy buffaloes and dairy workers causing localized pustules. the transmission of vacv to other susceptible ... | 2015 | 25804245 |
| molecular genetic analysis of orf virus: a poxvirus that has adapted to skin. | orf virus is the type species of the parapoxvirus genus of the family poxviridae. it induces acute pustular skin lesions in sheep and goats and is transmissible to humans. the genome is g+c rich, 138 kbp and encodes 132 genes. it shares many essential genes with vaccinia virus that are required for survival but encodes a number of unique factors that allow it to replicate in the highly specific immune environment of skin. phylogenetic analysis suggests that both viral interleukin-10 and vascular ... | 2015 | 25807056 |
| complement inhibition prevents oncolytic vaccinia virus neutralization in immune humans and cynomolgus macaques. | oncolytic viruses (ovs) have shown promising clinical activity when administered by direct intratumoral injection. however, natural barriers in the blood, including antibodies and complement, are likely to limit the ability to repeatedly administer ovs by the intravenous route. we demonstrate here that for a prototype of the clinical vaccinia virus based product pexa-vec, the neutralizing activity of antibodies elicited by smallpox vaccination, as well as the anamnestic response in hyperimmune v ... | 2015 | 25807289 |
| outbreak of severe zoonotic vaccinia virus infection, southeastern brazil. | in 2010, a vaccinia virus isolate caused an atypically severe outbreak that affected humans and cattle in brazil. of 26 rural workers affected, 12 were hospitalized. our data raise questions about the risk factors related to the increasing number and severity of vaccinia virus infections. | 2015 | 25811411 |
| cleavage of dicer protein by i7 protease during vaccinia virus infection. | dicer is the key component in the mirna pathway. degradation of dicer protein is facilitated during vaccinia virus (vv) infection. a c-terminal cleaved product of dicer protein was detected in the presence of mg132 during vv infection. thus, it is possible that dicer protein is cleaved by a viral protease followed by proteasome degradation of the cleaved product. there is a potential i7 protease cleavage site in the c-terminus of dicer protein. indeed, reduction of dicer protein was detected whe ... | 2015 | 25815818 |
| protective efficacy of the conserved np, pb1, and m1 proteins as immunogens in dna- and vaccinia virus-based universal influenza a virus vaccines in mice. | the conventional hemagglutinin (ha)- and neuraminidase (na)-based influenza vaccines need to be updated most years and are ineffective if the glycoprotein ha of the vaccine strains is a mismatch with that of the epidemic strain. universal vaccines targeting conserved viral components might provide cross-protection and thus complement and improve conventional vaccines. in this study, we generated dna plasmids and recombinant vaccinia viruses expressing the conserved proteins nucleoprotein (np), p ... | 2015 | 25834017 |
| evaluation of non-reciprocal heterologous immunity between unrelated viruses. | heterologous immunity refers to the phenomenon whereby a history of an immune response against one pathogen can provide a level of immunity to a second unrelated pathogen. previous investigations have shown that heterologous immunity is not necessarily reciprocal, such as in the case of vaccinia virus (vacv). replication of vacv is reduced in mice immune to a variety of pathogens, while vacv fails to induce immunity to several of the same pathogens, including lymphocytic choriomeningitis virus ( ... | 2015 | 25838115 |
| oncolytic poxviruses. | current standard treatments of cancer can prolong survival of many cancer patients but usually do not effectively cure the disease. oncolytic virotherapy is an emerging therapeutic for the treatment of cancer that exploits replication-competent viruses to selectively infect and destroy cancerous cells while sparing normal cells and tissues. clinical and/or preclinical studies on oncolytic viruses have revealed that the candidate viruses being tested in trials are remarkably safe and offer potent ... | 2014 | 25839047 |
| hiv specific responses induced in nonhuman primates with anrs hiv-lipo-5 vaccine combined with rmva-hiv prime or boost immunizations. | we evaluated the immunogenicity of a prime/boost vaccine strategy combining 5 lipopeptides (hiv-lipo-5) and a recombinant modified vaccinia virus ankara (rmva-hiv) in cynomolgus macaques. both of these vaccine components deliver hiv lai gag, pol, and nef antigens. systemic and local safety was excellent in all groups. immunization with hiv-lipo-5 alone induced significant serum anti-hiv antibody titers which were not modified by rmva-hiv immunization. however, induction of t-cell responses, as m ... | 2015 | 25839103 |
| erv enhances spatial learning and prevents the development of infarcts, accompanied by upregulated bdnf in the cortex. | an anti-allergic and analgesic drug, "an extract derived from the inflamed cutaneous tissue of rabbits inoculated with vaccinia virus (erv)", has been used in medical practice in japan and some other countries. we examined the effect of erv, prior to induction of ischemia, on the development of cerebral infarction, on learning and memory, or on brain-derived neurotrophic factor (bdnf) levels in c57bl/6j mice. | 2015 | 25842373 |
| hiv-1 vaccines based on replication-competent tiantan vaccinia protected chinese rhesus macaques from simian hiv infection. | to assess the efficacy of hiv vaccines constructed from replication-competent tiantan vaccinia virus (rtv) alone or combined with dna in protecting chinese rhesus macaques from homologous simian/human immunodeficiency virus (shiv)-cn97001 challenge. | 2015 | 25849828 |
| the evolution of poxvirus vaccines. | after edward jenner established human vaccination over 200 years ago, attenuated poxviruses became key players to contain the deadliest virus of its own family: variola virus (varv), the causative agent of smallpox. cowpox virus (cpxv) and horsepox virus (hspv) were extensively used to this end, passaged in cattle and humans until the appearance of vaccinia virus (vacv), which was used in the final campaigns aimed to eradicate the disease, an endeavor that was accomplished by the world health or ... | 2015 | 25853483 |
| genetic confirmation that the h5 protein is required for vaccinia virus dna replication. | the duplication of the poxvirus double-stranded dna genome occurs in cytoplasmic membrane-delimited factories. this physical autonomy from the host nucleus suggests that poxvirus genomes encode the full repertoire of proteins committed for genome replication. biochemical and genetic analyses have confirmed that six viral proteins are required for efficient dna synthesis; indirect evidence has suggested that the multifunctional h5 protein may also have a role. here we show that h5 localizes to re ... | 2015 | 25855734 |
| the vaccinia virus e6 protein influences virion protein localization during virus assembly. | vaccinia virus mutants in which expression of the virion core protein gene e6r is repressed are defective in virion morphogenesis. e6 deficient infections fail to properly package viroplasm into viral membranes, resulting in an accumulation of empty immature virions and large aggregates of viroplasm. we have used immunogold electron microscopy and immunofluorescence confocal microscopy to assess the intracellular localization of several virion structural proteins and enzymes during e6r mutant in ... | 2015 | 25863879 |
| [a novel immunization strategy to induce strong humoral responses against hiv-1 using combined dna, recombinant vaccinia virus and protein vaccines]. | to optimize the immunization strategy against hiv-1, a dna vaccine was combined with a recombinant vaccinia virus (rtv) vaccine and a protein vaccine. immune responses against hiv-1 were detected in 30 female guinea pigs divided into six groups. three groups of guinea pigs were primed with hiv-1 dna vaccine three times, boosted with rtv at week 14, and then boosted with gp140 protein at intervals of 4, 8 or 12 weeks. simultaneously, the other three groups of animals were primed with rtv vaccine ... | 2014 | 25868279 |
| vaccinia virus infection requires maturation of macropinosomes. | the prototypic poxvirus, vaccinia virus (vacv), occurs in two infectious forms, mature virions (mvs) and extracellular virions (evs). both enter hela cells by inducing macropinocytic uptake. using confocal microscopy, live-cell imaging, targeted rnai screening and perturbants of endosome maturation, we analyzed the properties and maturation pathway of the macropinocytic vacuoles containing vacv mvs in hela cells. the vacuoles first acquired markers of early endosomes [rab5, early endosome antige ... | 2015 | 25869659 |
| immunomodulator-based enhancement of anti smallpox immune responses. | the current live vaccinia virus vaccine used in the prevention of smallpox is contraindicated for millions of immune-compromised individuals. although vaccination with the current smallpox vaccine produces protective immunity, it might result in mild to serious health complications for some vaccinees. thus, there is a critical need for the production of a safe virus-free vaccine against smallpox that is available to everyone. for that reason, we investigated the impact of imiquimod and resiquimo ... | 2015 | 25875833 |
| lister strain vaccinia virus with thymidine kinase gene deletion is a tractable platform for development of a new generation of oncolytic virus. | vaccinia virus (vv) has many attractive characteristics as a potential cancer therapeutic. there are several strains of vv. the nonvaccine strain western reserve vv with deletion of both the thymidine kinase and the viral growth factor genes (known as wrdd) has been reported as the most potent tumor-targeted oncolytic vv. other strains, such as the european vaccine lister strain, are largely untested. this study evaluated the antitumor potency and biodistribution of different vv strains using in ... | 2015 | 25876464 |
| cardiac safety of modified vaccinia ankara for vaccination against smallpox in a young, healthy study population. | conventional smallpox vaccines based on replicating vaccinia virus (vv) strains (e.g. lister elstree, nycboh) are associated with a high incidence of myo-/pericarditis, a severe inflammatory cardiac complication. a new smallpox vaccine candidate based on a non-replicating modified vaccinia ankara (mva) poxvirus has been assessed for cardiac safety in a large placebo-controlled clinical trial. | 2015 | 25879867 |
| characterization of hiv-1 entry inhibitors with broad activity against r5 and x4 viral strains. | combined antiretroviral therapy has drastically reduced mortality and morbidity of hiv-infected individuals. nevertheless long-term toxicity and appearance of viral resistance hampers the prolonged effectiveness of combination therapy, requiring a continuous input of drugs to replace those utilized in combination regimens. we here investigated the anti-hiv activity of novel derivatives of the suradista chemical class. | 2015 | 25888743 |
| the mechanisms of genetically modified vaccinia viruses for the treatment of cancer. | the use of oncolytic viruses for the treatment of cancer is an emerging field of cancer research and therapy. oncolytic viruses are designed to induce tumor specific immunity while replicating selectively within cancer cells to cause lysis of the tumor cells. while there are several forms of oncolytic viruses, the use of vaccinia viruses for oncolysis may be more beneficial than other forms of oncolytic viruses. for example, vaccinia viruses have been shown to exert their anti-tumor effects thro ... | 2015 | 25900073 |
| deciphering poxvirus gene expression by rna sequencing and ribosome profiling. | the more than 200 closely spaced annotated open reading frames, extensive transcriptional read-through, and numerous unpredicted rna start sites have made the analysis of vaccinia virus gene expression challenging. genome-wide ribosome profiling provided an unprecedented assessment of poxvirus gene expression. by 4 h after infection, approximately 80% of the ribosome-associated mrna was viral. ribosome-associated mrnas were detected for most annotated early genes at 2 h and for most intermediate ... | 2015 | 25903347 |
| laboratory-acquired vaccinia virus infection in a recently immunized person--massachusetts, 2013. | on november 26, 2013, the cdc poxvirus laboratory was notified by the boston public health commission (bphc) of an inadvertent inoculation of a recently vaccinated (acam2000 smallpox vaccine) laboratory worker with wild type vaccinia virus (vacv) western reserve. a joint investigation by cdc and bphc confirmed orthopoxvirus infection in the worker, who had reported a needle stick in his thumb while inoculating a mouse with vacv. he experienced a non-tender, red rash on his arm, diagnosed at a lo ... | 2015 | 25928468 |
| smallpox vaccine, acam2000: sites and duration of viral shedding and effect of povidone iodine on scarification site shedding and immune response. | the u.s. department of defense vaccinates personnel deployed to high-risk areas with the vaccinia virus (vacv)-based smallpox vaccine. autoinoculations and secondary and tertiary transmissions due to vacv shedding from the vaccination site continue to occur despite education of vaccinees on the risks of such infections. the objectives of this study were to investigate, in naïve smallpox vaccinees, (a) whether the vaccination site can remain contagious after the scab separates and (b) whether the ... | 2015 | 25930115 |
| socs1 mimetics and antagonists: a complementary approach to positive and negative regulation of immune function. | suppressors of cytokine signaling (socs) are inducible intracellular proteins that play essential regulatory roles in both immune and non-immune function. of the eight known members, socs1 and socs3 in conjunction with regulatory t cells play key roles in regulation of the immune system. molecular tools such as gene transfections and sirna have played a major role in our functional understanding of the socs proteins where a key functional domain of 12-amino acid residues called the kinase inhibi ... | 2015 | 25954276 |
| modification of promoter spacer length in vaccinia virus as a strategy to control the antigen expression. | vaccinia viruses (vacvs) with distinct early promoters have been developed to enhance antigen expression and improve antigen-specific cd8 t-cell responses. it has not been demonstrated how the length of the spacer between the coding region of the gene and its regulatory early promoter motif influences antigen expression, and whether the timing of gene expression can modify the antigen-specific cd4 t-cell response. we generated several recombinant vacvs based on the attenuated modified vaccinia a ... | 2015 | 25972354 |
| oncolytic viruses: from bench to bedside with a focus on safety. | oncolytic viruses are a relatively new class of anti-cancer immunotherapy agents. several viruses have undergone evaluation in clinical trials in the last decades, and the first agent is about to be approved to be used as a novel cancer therapy modality. in the current review, an overview is presented on recent (pre)clinical developments in the field of oncolytic viruses that have previously been or currently are being evaluated in clinical trials. special attention is given to possible safety i ... | 2015 | 25996182 |