Publications
| Title | Abstract | Year Filter | PMID(sorted ascending) Filter |
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| xcr1+ dendritic cells promote memory cd8+ t cell recall upon secondary infections with listeria monocytogenes or certain viruses. | naive cd8(+) t cell priming during tumor development or many primary infections requires cross-presentation by xcr1(+) dendritic cells (dcs). memory cd8(+) t lymphocytes (mctls) harbor a lower activation threshold as compared with naive cells. however, whether their recall responses depend on xcr1(+) dcs is unknown. by using a new mouse model allowing fluorescent tracking and conditional depletion of xcr1(+) dcs, we demonstrate a differential requirement of these cells for mctl recall during sec ... | 2016 | 26694969 |
| [modified vaccinia virus ankara (mva)--development as recombinant vaccine and prospects for use in veterinary medicine]. | poxviruses as expression vectors are widely used in medical research for the development of recombinant vaccines and molecular therapies. here we review recent accomplishments in vaccine research using recombinant modified vaccinia virus ankara (mva). mva is a highly attenuated vaccinia virus strain that originated from serial tissue culture passage in chicken embryo fibroblasts more than 40 years ago. growth adaptation to avian host cells caused deletions and mutations in the viral genome affec ... | 2015 | 26697713 |
| regulation of macropinocytosis by diacylglycerol kinase ζ. | macropinosomes arise from the closure of plasma membrane ruffles to bring about the non-selective uptake of nutrients and solutes into cells. the morphological changes underlying ruffle formation and macropinosome biogenesis are driven by actin cytoskeleton rearrangements under the control of the rho gtpase rac1. we showed previously that rac1 is activated by diacylglycerol kinase ζ (dgkζ), which phosphorylates diacylglycerol to yield phosphatidic acid. here, we show dgkζ is required for optimal ... | 2015 | 26701304 |
| oral immunization with recombinant vaccinia virus prime and intramuscular protein boost provides protection against intrarectal simian-human immunodeficiency virus challenge in macaques. | human immunodeficiency virus type 1 (hiv-1) acquisition occurs predominantly through mucosal transmission. we hypothesized that greater mucosal immune responses and protective efficacy against mucosal hiv-1 infection may be achieved by prime-boost immunization at mucosal sites. we used a macaque model to determine the safety, immunogenicity, and protective efficacy of orally delivered, replication-competent but attenuated recombinant vaccinia viruses expressing full-length hiv-1 sf162 envelope ( ... | 2015 | 26718849 |
| protection against lethal vaccinia virus infection in mice using an sirna targeting the a5r gene. | although the world health organization has declared the eradication of smallpox in 1980, the fear of its potential use in bioterrorism has become a reality. since the effectiveness of current vaccines and antiviral drugs is limited, development of new therapeutic strategies is needed. in this study, we investigated small interfering rna (sirna) as a therapeutic approach for preventing and treating smallpox infection. | 2016 | 26741698 |
| viral infection causes a shift in the self peptide repertoire presented by human mhc class i molecules. | mhc class i presentation of peptides allows t cells to survey the cytoplasmic protein milieu of host cells. during infection, presentation of self peptides is, in part, replaced by presentation of microbial peptides. however, little is known about the self peptides presented during infection, despite the fact that microbial infections alter host cell gene expression patterns and protein metabolism. | 2015 | 26768311 |
| features of the antitumor effect of vaccinia virus lister strain. | oncolytic abilities of vaccinia virus (vacv) served as a basis for the development of various recombinants for treating cancer; however, "natural" oncolytic properties of the virus are not examined in detail. our study was conducted to know how the genetically unmodified l-ivp strain of vacv produces its antitumor effect. human a431 carcinoma xenografts in nude mice and murine ehrlich carcinoma in c57bl mice were used as targets for vacv, which was injected intratumorally. a set of virological m ... | 2016 | 26771631 |
| the acidic c-terminus of vaccinia virus i3 single-strand binding protein promotes proper assembly of dna-protein complexes. | the vaccinia virus i3l gene encodes a single-stranded dna binding protein (ssb) that is essential for virus dna replication and is conserved in all chordopoxviruses. the i3 protein contains a negatively charged c-terminal tail that is a common feature of ssbs. such acidic tails are critical for ssb-dependent replication, recombination and repair. we cloned and purified variants of the i3 protein, along with a homolog from molluscum contagiosum virus, and tested how the acidic tail affected dna-p ... | 2016 | 26773382 |
| attenuation of vaccinia virus. | since 1980, in the post-smallpox vaccination era the human population has become increasingly susceptible compared to a generation ago to not only the variola (smallpox) virus, but also other zoonotic orthopoxviruses. the need for safer vaccines against orthopoxviruses is even greater now. the lister vaccine strain (livp) of vaccinia virus was used as a parental virus for generating a recombinant 1421abjcn clone defective in five virulence genes encoding hemagglutinin (a56r), the ifn-γ-binding p ... | 2017 | 26798498 |
| oncolytic and immunologic cancer therapy with gm-csf-armed vaccinia virus of tian tan strain guang9. | targeted oncolytic vaccinia viruses are being developed as a novel strategy in cancer therapy. arming vaccinia viruses with immunostimulatory cytokines can enhance antitumor efficacy. such engineered oncolytic viruses, like jx-594, a wyeth strain vaccinia virus modified with human granulocyte-macrophage colony-stimulating factor (gm-csf), have shown promising results and have proceeded rapidly in clinical trials. however, the oncolytic potential of the chinese vaccine strain tian tan (vtt) has n ... | 2016 | 26803055 |
| dogs and opossums positive for vaccinia virus during outbreak affecting cattle and humans, são paulo state, brazil. | during a vaccinia virus (vacv) outbreak in são paulo state, brazil, blood samples were collected from cows, humans, other domestic animals, and wild mammals. samples from 3 dogs and 3 opossums were positive for vacv by pcr. results of gene sequencing yielded major questions regarding other mammalian species acting as reservoirs of vacv. | 2016 | 26812352 |
| oncolytic vaccinia virus as a vector for therapeutic sodium iodide symporter gene therapy in prostate cancer. | oncolytic strains of vaccinia virus are currently in clinical development with clear evidence of safety and promising signs of efficacy. addition of therapeutic genes to the viral genome may increase the therapeutic efficacy of vaccinia. we evaluated the therapeutic potential of vaccinia virus expressing the sodium iodide symporter (nis) in prostate cancer models, combining oncolysis, external beam radiotherapy and nis-mediated radioiodide therapy. the nis-expressing vaccinia virus (vv-nis), glv ... | 2016 | 26814609 |
| seven major genomic deletions of vaccinia virus tiantan strain are sufficient to decrease pathogenicity. | attenuated strain ttvac7, as a multi-gene-deleted vaccinia virus tiantan strain (vtt), was constructed by knocking out parts of non-essential genes related to virulence, host range and immunomodulation of vtt, and by combining double marker screening with exogenous selectable marker knockout techniques. in this study, shuttle vector plasmids ptc-egfp, pta35-egfp, pta66-egfp, pte-egfp, ptb-egfp, pti-egfp and ptj-egfp were constructed, which contained seven pairs of recombinant arms linked to the ... | 2016 | 26821204 |
| destabilization of α-helical structure in solution improves bactericidal activity of antimicrobial peptides: opposite effects on bacterial and viral targets. | we have previously examined the mechanism of antimicrobial peptides on the outer membrane of vaccinia virus. we show here that the formulation of peptides ll37 and magainin-2b amide in polysorbate 20 (tween 20) results in greater reductions in virus titer than formulation without detergent, and the effect is replicated by substitution of polysorbate 20 with high-ionic-strength buffer. in contrast, formulation with polysorbate 20 or high-ionic-strength buffer has the opposite effect on bactericid ... | 2016 | 26824944 |
| position on reproductive donors and smallpox vaccine: a committee opinion. | although there is presently no definitive evidence linking vaccinia virus transmission through reproductive cells, the society for assisted reproductive technology (sart) and the american society for reproductive medicine (asrm) accordingly recommend that assisted reproductive technology (art) practitioners consider deferring individuals who are planning on donating gametes for reproductive use (reproductive donors) who have recently received smallpox vaccine or contracted symptomatic vaccinia v ... | 2016 | 26829211 |
| thymic stromal lymphopoietin and il-33 promote skin inflammation and vaccinia virus replication in a mouse model of atopic dermatitis. | 2016 | 26830114 | |
| evaluation of quantum dot immunofluorescence and a digital cmos imaging system as an alternative to conventional organic fluorescence dyes and laser scanning for quantifying protein microarrays. | organic fluorescent dyes are widely used for the visualization of bound antibody in a variety of immunofluorescence assays. however, the detection equipment is often expensive, fragile, and hard to deploy widely. quantum dots (qdot) are nanocrystals made of semiconductor materials that emit light at different wavelengths according to the size of the crystal, with increased brightness and stability. here, we have evaluated a small benchtop "personal" optical imager (arraycam) developed for quanti ... | 2016 | 26842269 |
| activation of rnase l is dependent on oas3 expression during infection with diverse human viruses. | the 2',5'-oligoadenylate (2-5a) synthetase (oas)-rnase l system is an ifn-induced antiviral pathway. rnase l activity depends on 2-5a, synthesized by oas. although all three enzymatically active oas proteins in humans--oas1, oas2, and oas3--synthesize 2-5a upon binding dsrna, it is unclear which are responsible for rnase l activation during viral infection. we used clustered regularly interspaced short palindromic repeats (crispr)-crispr-associated protein-9 nuclease (cas9) technology to enginee ... | 2016 | 26858407 |
| development and virucidal activity of a novel alcohol-based hand disinfectant supplemented with urea and citric acid. | hand disinfectants are important for the prevention of virus transmission in the health care system and environment. the development of broad antiviral spectrum hand disinfectants with activity against enveloped and non-enveloped viruses is limited due to a small number of permissible active ingredients able to inactivate viruses. | 2016 | 26864562 |
| detection of vaccinia virus during an outbreak of exanthemous oral lesions in brazilian equids. | in august 2014, an outbreak of oral exanthematous disease in equids was reported in brazil, affecting 11 donkeys and 3 mules. | 2017 | 26875684 |
| linear epitopes in vaccinia virus a27 are targets of protective antibodies induced by vaccination against smallpox. | vaccinia virus (vacv) a27 is a target for viral neutralization and part of the dryvax smallpox vaccine. a27 is one of the three glycosaminoglycan (gag) adhesion molecules and binds to heparan sulfate. to understand the function of anti-a27 antibodies, especially their protective capacity and their interaction with a27, we generated and subsequently characterized 7 murine monoclonal antibodies (mabs), which fell into 4 distinct epitope groups (groups i to iv). the mabs in three groups (groups i, ... | 2016 | 26889021 |
| molluscum contagiosum virus transcriptome in abortively infected cultured cells and a human skin lesion. | molluscum contagiosum virus (mocv), the only circulating human-specific poxvirus, has a worldwide distribution and causes benign skin lesions that may persist for months in young children and severe infections in immunosuppressed adults. studies of mocv are restricted by the lack of an efficient animal model or a cell culture replication system. we used next-generation sequencing to analyze and compare polyadenylated rnas from abortive mocv infections of several cell lines and a human skin lesio ... | 2016 | 26889040 |
| myxoma virus m156 is a specific inhibitor of rabbit pkr but contains a loss-of-function mutation in australian virus isolates. | myxoma virus (myxv) is a rabbit-specific poxvirus, which is highly virulent in european rabbits. the attenuation of myxv and the increased resistance of rabbits following the release of myxv in australia is one of the best-documented examples of host-pathogen coevolution. to elucidate the molecular mechanisms that contribute to the restriction of myxv infection to rabbits and myxv attenuation in the field, we have studied the interaction of the myxv protein m156 with the host antiviral protein k ... | 2016 | 26903626 |
| domain organization of vaccinia virus helicase-primase d5. | poxviridae are viruses with a large linear double-stranded dna genome coding for up to 250 open reading frames and a fully cytoplasmic replication. the double-stranded dna genome is covalently circularized at both ends. similar structures of covalently linked extremities of the linear dna genome are found in the african swine fever virus (asfarvirus) and in the phycodnaviridae we are studying the machinery which replicates this peculiar genome structure. from our work with vaccinia virus, we giv ... | 2016 | 26912611 |
| vaccinia virus-free rescue of fluorescent replication-defective vesicular stomatitis virus and pseudotyping with puumala virus glycoproteins for use in neutralization tests. | puumala virus (puuv) grows slowly in cell culture. to study antigenic properties of puuv, an amenable method for their expression would be beneficial. to achieve this, a replication-defective recombinant vesicular stomatitis virus, rvsvδg*egfp, was rescued using bsrt7/5 and encephalomyocarditis virus (emcv) internal ribosomal entry site (ires)-enabled rescue plasmids. using these particles, pseudotypes bearing puuv sotkamo strain glycoproteins were produced, with titres in the range 105-108, and ... | 2016 | 26916544 |
| a cancer-favoring oncolytic vaccinia virus shows enhanced suppression of stem-cell like colon cancer. | stem cell-like colon cancer cells (sccs) pose a major challenge in colon cancer treatment because of their resistance to chemotherapy and radiotherapy. oncolytic virus-based therapy has shown promising results in uncured cancer patients; however, its effects on sccs are not well studied yet. here, we engineered a cancer-favoring oncolytic vaccinia virus (cvv) as a potent biotherapeutic and investigated its therapeutic efficacy in terms of killing sccs. cvv is an evolved wyeth strain vaccinia vir ... | 2016 | 26918725 |
| the vaccinia virus h3 envelope protein, a major target of neutralizing antibodies, exhibits a glycosyltransferase fold and binds udp-glucose. | the highly conserved h3 poxvirus protein is a major target of the human antibody response against poxviruses and is likely a key contributor to protection against infection. here, we present the crystal structure of h3 from vaccinia virus at a 1.9-å resolution. h3 looks like a glycosyltransferase, a family of enzymes that transfer carbohydrate molecules to a variety of acceptor substrates. like glycosyltransferases, h3 binds udp-glucose, as shown by saturation transfer difference (std) nuclear m ... | 2016 | 26937025 |
| pkr transduces mda5-dependent signals for type i ifn induction. | sensing invading pathogens early in infection is critical for establishing host defense. two cytosolic rig-like rna helicases, rig-i and mda5, are key to type i interferon (ifn) induction in response to viral infection. mounting evidence suggests that another viral rna sensor, protein kinase r (pkr), may also be critical for ifn induction during infection, although its exact contribution and mechanism of action are not completely understood. using pkr-deficient cells, we found that pkr was requi ... | 2016 | 26939124 |
| the improved antibody response against hiv-1 after a vaccination based on intrastructural help is complemented by functional cd8+ t cell responses. | despite more than three decades of intense research, a prophylactic hiv-1 vaccine remains elusive. four vaccine modalities have been evaluated in clinical efficacy studies, but only one demonstrated at least modest efficacy, which correlated with polyfunctional antibody responses to the hiv surface protein env. to be most effective, a hiv-1 vaccine probably has to induce both, functional antibody and cd8(+) t cell responses. we therefore analyzed dna/dna and dna/virus-like particle (vlp) regimen ... | 2016 | 26945099 |
| crispr-cas9 as a powerful tool for efficient creation of oncolytic viruses. | the development of oncolytic viruses has led to an emerging new class of cancer therapeutics. although the safety profile has been encouraging, the transition of oncolytic viruses to the clinical setting has been a slow process due to modifications. therefore, a new generation of more potent oncolytic viruses needs to be exploited, following our better understanding of the complex interactions between the tumor, its microenvironment, the virus, and the host immune response. the conventional meth ... | 2016 | 26959050 |
| exploring the purine core of 3'-c-ethynyladenosine (eado) in search of novel nucleoside therapeutics. | a series of new nucleoside analogues based on a c-3 branched ethynyl sugar derivative as present in 3'-c-ethynylcytidine (ecyd) and -adenosine (eado), combined with modified purine bases was synthetized and evaluated against a broad array of viruses and tumour cell lines. the pronounced cytostatic activity of eado was confirmed. eado and its 2,6-diaminopurine analogue showed inhibitory activity against vaccinia virus (ec50: 0.31 and 51 μm, respectively). derivative 10 on the other hand was found ... | 2016 | 26965865 |
| use of vaccinia virus smallpox vaccine in laboratory and health care personnel at risk for occupational exposure to orthopoxviruses - recommendations of the advisory committee on immunization practices (acip), 2015. | on june 25, 2015, the advisory committee on immunization practices (acip) recommended routine vaccination with live smallpox (vaccinia) vaccine (acam2000) for laboratory personnel who directly handle 1) cultures or 2) animals contaminated or infected with replication-competent vaccinia virus, recombinant vaccinia viruses derived from replication-competent vaccinia strains (i.e., those that are capable of causing clinical infection and producing infectious virus in humans), or other orthopoxvirus ... | 2016 | 26985679 |
| locally produced il-10 limits cutaneous vaccinia virus spread. | skin infection with the poxvirus vaccinia (vv) elicits a powerful, inflammatory cellular response that clears virus infection in a coordinated, spatially organized manner. given the high concentration of pro-inflammatory effectors at areas of viral infection, it is unclear how tissue pathology is limited while virus-infected cells are being eliminated. to better understand the spatial dynamics of the anti-inflammatory response to a cutaneous viral infection, we first screened cytokine mrna expre ... | 2016 | 26991092 |
| defining viral defective ribosomal products: standard and alternative translation initiation events generate a common peptide from influenza a virus m2 and m1 mrnas. | influenza a virus gene segment 7 encodes two proteins: the m1 protein translated from unspliced mrna and the m2 protein produced by mrna splicing and largely encoded by the m1 +1 reading frame. to better understand the generation of defective ribosomal products relevant to mhc class i ag presentation, we engineered influenza a virus gene segment 7 to encode the model h-2 k(b) class i peptide ligand siinfekl at the m2 protein c terminus. remarkably, after treating virus-infected cells with the rn ... | 2016 | 27016602 |
| highly immunogenic variant of attenuated vaccinia virus. | the livpδ6 strain of vaccinia virus (vacv) was created by genetic engineering on the basis of previously obtained attenuated 1421abjcn strain by target deletion of the a35r gene encoding an inhibitor of antigen presentation by the major histocompatibility complex class ii. 1421abjcn is the livp strain of vacv with five inactivated virulence genes encoding hemagglutinin (a56r), γ-interferon-binding protein (b8r), thymidine kinase (j2r), complement-binding protein (c3l), and bcl2-like inhibitor of ... | 2016 | 27025484 |
| erratum to: a novel vaccinia virus with dual oncolytic and anti-angiogenic therapeutic effects against triple-negative breast cancer. | 2016 | 27026359 | |
| maternal antibiotic treatment impacts development of the neonatal intestinal microbiome and antiviral immunity. | microbial colonization of the infant gastrointestinal tract (git) begins at birth, is shaped by the maternal microbiota, and is profoundly altered by antibiotic treatment. antibiotic treatment of mothers during pregnancy influences colonization of the git microbiota of their infants. the role of the git microbiota in regulating adaptive immune function against systemic viral infections during infancy remains undefined. we used a mouse model of perinatal antibiotic exposure to examine the effect ... | 2016 | 27036912 |
| nyvac vector modified by c7l viral gene insertion improves t cell immune responses and effectiveness against leishmaniasis. | the nyvac poxvirus vector is used as vaccine candidate for hiv and other diseases, although there is only limited experimental information on its immunogenicity and effectiveness for use against human pathogens. here we defined the selective advantage of nyvac vectors in a mouse model by comparing the immune responses and protection induced by vectors that express the lack (leishmania-activated c-kinase antigen), alone or with insertion of the viral host range gene c7l that allows the virus to r ... | 2016 | 27036935 |
| defending against smallpox: a focus on vaccines. | smallpox has shaped human history, from the earliest human civilizations well into the 20th century. with high mortality rates, rapid transmission, and serious long-term effects on survivors, smallpox was a much-feared disease. the eradication of smallpox represents an unprecedented medical victory for the lasting benefit of human health and prosperity. concerns remain, however, about the development and use of the smallpox virus as a biological weapon, which necessitates the need for continued ... | 2016 | 27049653 |
| an interaction quantitative trait loci tool implicates epistatic functional variants in an apoptosis pathway in smallpox vaccine eqtl data. | expression quantitative trait loci (eqtl) studies have functionalized nucleic acid variants through the regulation of gene expression. although most eqtl studies only examine the effects of single variants on transcription, a more complex process of variant-variant interaction (epistasis) may regulate transcription. herein, we describe a tool called interaction qtl (iqtl) designed to efficiently detect epistatic interactions that regulate gene expression. to maximize biological relevance and min ... | 2016 | 27052692 |
| influenza neuraminidase subtype n1: immunobiological properties and functional assays for specific antibody response. | influenza neuraminidase (na) proteins expressed in tk- cells infected with recombinant vaccinia virus carrying na gene of highly pathogenic avian influenza h5n1 virus or 2009 pandemic h1n1 (h1n1pdm) virus were characterized for their biological properties, i.e., cell localization, molecular weight (mw), glycosylation and sialidase activity. immune sera collected from balb/c mice immunized with these recombinant viruses were assayed for binding and functional activities of anti-na antibodies. rec ... | 2016 | 27054879 |
| oncolytic virotherapy with an armed vaccinia virus in an orthotopic model of renal carcinoma is associated with modification of the tumor microenvironment. | oncolytic virotherapy is an emergent promising therapeutic approach for the treatment of cancer. we have constructed a vaccinia virus (wr strain) deleted for thymidine kinase (tk) and ribonucleotide reductase (rr) genes that expressed the fusion suicide gene fcu1 derived from the yeast cytosine deaminase and uracil phosphoribosyltransferase genes. we evaluated this construct (vv-fcu1) in the orthotopic model of renal carcinoma (renca). systemic administration of vv-fcu1 resulted in orthotopic tu ... | 2016 | 27057460 |
| targeting hiv-1 env gp140 to lox-1 elicits immune responses in rhesus macaques. | improved antigenicity against hiv-1 envelope (env) protein is needed to elicit vaccine-induced protective immunity in humans. here we describe the first tests in non-human primates (nhps) of env gp140 protein fused to a humanized anti-lox-1 recombinant antibody for delivering env directly to lox-1-bearing antigen presenting cells, especially dendritic cells (dc). lox-1, or 1ectin-like oxidized low-density lipoprotein (ldl) receptor-1, is expressed on various antigen presenting cells and endothel ... | 2016 | 27077384 |
| human hepatocytes express absent in melanoma 2 and respond to hepatitis b virus with interleukin-18 expression. | absent in melanoma 2 (aim2) is a recently recognized cytoplasmic receptor which could sense cytoplasmic double-stranded dna (dsdna). after aim2 detects the presence of parasitic nucleic acids (dsdna) derived from invasive bacteria or viral genomes (for example, vaccinia virus and cytomegalovirus) within infected cells, aim2 inflammasome could be formed. the formed aim2 inflammasome could induce innate immune response and increase expressions of il-1β and il-18. hepatitis b virus (hbv) is a hepat ... | 2016 | 27094165 |
| isolated limb perfusion with biochemotherapy and oncolytic virotherapy combines with radiotherapy and surgery to overcome treatment resistance in an animal model of extremity soft tissue sarcoma. | the management of locally advanced or recurrent extremity sarcoma often necessitates multimodal therapy to preserve a limb, of which isolated limb perfusion (ilp) is a key component. however, with standard chemotherapeutic agents used in ilp, the duration of response is limited. novel agents or treatment combinations are urgently needed to improve outcomes. previous work in an animal model has demonstrated the efficacy of oncolytic virotherapy when delivered by ilp and, in this study, we report ... | 2016 | 27116656 |
| safety and biodistribution of a double-deleted oncolytic vaccinia virus encoding cd40 ligand in laboratory beagles. | we evaluated adverse events, biodistribution and shedding of oncolytic vaccinia virus encoding cd40 ligand in two beagles, in preparation for a phase 1 trial in canine cancer patients. dog 1 received one dose of vaccinia virus and was euthanized 24 hours afterwards, while dog 2 received virus four times once weekly and was euthanized 7 days after that. dogs were monitored for adverse events and underwent a detailed postmortem examination. blood, saliva, urine, feces, and organs were collected fo ... | 2014 | 27119092 |
| overcoming tumor resistance by heterologous adeno-poxvirus combination therapy. | successful cancer control relies on overcoming resistance to cell death and on activation of host antitumor immunity. oncolytic viruses are particularly attractive in this regard, as they lyse infected tumor cells and trigger robust immune responses during the infection. however, repeated injections of the same virus promote antiviral rather than antitumor immunity and tumors may mount innate antiviral defenses to restrict oncolytic virus replication. in this article, we have explored if alterna ... | 2015 | 27119097 |
| expression of anti-vegf antibody together with anti-egfr or anti-fap enhances tumor regression as a result of vaccinia virotherapy. | the tumor microenvironment plays an important role in tumor growth and progression. here we demonstrate that vaccinia virus-mediated, constitutively expressed intratumoral antibodies against vascular endothelial growth factor (vegf), epidermal growth factor receptor (egfr), and fibroblast activation protein (fap) significantly improved tumor regression and oncolytic virotherapy through suppression of angiogenesis, cell proliferation, and stromagenesis in virus-colonized tumors. in contrast to th ... | 2015 | 27119102 |
| intratumoral inf-γ triggers an antiviral state in gl261 tumor cells: a major hurdle to overcome for oncolytic vaccinia virus therapy of cancer. | oncolytic vaccinia virus (vacv) therapy is an alternative treatment option for glioblastoma multiforme. here, we used a comparison of different tumor locations and different immunologic and genetic backgrounds to determine the replication efficacy and oncolytic potential of the vacv livp 1.1.1, an attenuated wild-type isolate of the lister strain, in murine gl261 glioma models. with this approach, we expected to identify microenvironmental factors, which may be decisive for failure or success of ... | 2015 | 27119106 |
| evidence for differential viral oncolytic efficacy in an in vitro model of epithelial ovarian cancer metastasis. | epithelial ovarian cancer is unique among most carcinomas in that metastasis occurs by direct dissemination of malignant cells traversing throughout the intraperitoneal fluid. accordingly, we test new therapeutic strategies using an in vitro three-dimensional spheroid suspension culture model that mimics key steps of this metastatic process. in the present study, we sought to uncover the differential oncolytic efficacy among three different viruses-myxoma virus, double-deleted vaccinia virus, an ... | 2015 | 27119108 |
| cxcl11-armed oncolytic poxvirus elicits potent antitumor immunity and shows enhanced therapeutic efficacy. | we have armed a tumor-selective oncolytic vaccinia virus (vvdd) with the chemokine (ck) cxcl11, in order to enhance its ability to attract cxcr3(+) antitumor ctls and possibly nk cells to the tumor microenvironment (tme) and improve its therapeutic efficacy. as expected, vvdd-cxcl11 attracted high numbers of tumor-specific t cells to the tme in a murine ab12 mesothelioma model. intratumoral virus-directed cxcl11 expression enhanced local numbers of cd8(+) ctls and levels of granzyme b, while red ... | 2016 | 27141352 |
| goatpoxvirus atpase activity is increased by dsdna and decreased by zinc ion. | viral-encoded atpase can act as a part of molecular motor in genome packaging of dna viruses, such as vaccinia virus and adenovirus, by atp hydrolysis and interaction with dna. poxviral atpase (also called a32) is involved in genomic double-stranded dna (dsdna) encapsidation, and inhibition of the expression of a32 causes formation of immature virions lacking viral dna. however, the role of a32 in goatpoxvirus genome packaging and its dsdna binding property are not known. in this study, purified ... | 2016 | 27146321 |
| cd69 deficiency enhances the host response to vaccinia virus infection through altered nk cell homeostasis. | during the host response to viral infection, the transmembrane cd69 protein is highly upregulated in all immune cells. we have studied the role of cd69 in the murine immune response to vaccinia virus (vacv) infection, and we report that the absence of cd69 enhances protection against vacv at both short and long times postinfection in immunocompetent and immunodeficient mice. natural killer (nk) cells were implicated in the increased infection control, since the differences were greatly diminishe ... | 2016 | 27147744 |
| suppression of kaposi's sarcoma-associated herpesvirus infection and replication by 5'-amp-activated protein kinase. | the host intracellular antiviral restriction factors inhibit viral infection and replication. the 5'-amp-activated protein kinase (ampk) is a cellular energy sensor regulating metabolic homeostasis. activated ampk inhibits the replication of numerous rna viruses but enhances the entry of vaccinia virus. however, the role of ampk in herpesvirus infection is unclear. in this study, we showed that the constitutive ampk activity restricted kaposi's sarcoma-associated herpesvirus (kshv) lytic replica ... | 2016 | 27147746 |
| identification and characterization of a cleavage site in the proteolysis of orf virus 086 protein. | the orf virus (orfv) is among the parapoxvirus genus of the poxviridae family, but little is known about the proteolytic pathways of orfv encoding proteins. by contrast, the proteolysis mechanism of the vaccinia virus (vv) has been extensively explored. vaccinia virus core protein p4a undergoes a proteolytic process that takes place at a conserved cleavage site ala-gly-x (where x is any amino acid) and participates in virus assembly. bioinformatics analysis revealed that an orfv encoding protein ... | 2016 | 27148226 |
| the n terminus of the vaccinia virus protein f1l is an intrinsically unstructured region that is not involved in apoptosis regulation. | subversion of host cell apoptotic responses is a prominent feature of viral immune evasion strategies to prevent premature clearance of infected cells. numerous poxviruses encode structural and functional homologs of the bcl-2 family of proteins, and vaccinia virus harbors antiapoptotic f1l that potently inhibits the mitochondrial apoptotic checkpoint. recently f1l has been assigned a caspase-9 inhibitory function attributed to an n-terminal α helical region of f1l spanning residues 1-15 (1) pre ... | 2016 | 27151220 |
| an improved high pressure freezing and freeze substitution method to preserve the labile vaccinia virus nucleocapsid. | in recent years, high pressure freezing and freeze substitution have been widely used for electron microscopy to reveal viral and cellular structures that are difficult to preserve. vaccinia virus, a member of the poxviridae family, presents one of the most complex viral structures. the classical view of vaccinia virus structure consists of an envelope surrounding a biconcave core, with a lateral body in each concavity of the core. this classical view was challenged by peters and muller (1963), ... | 2016 | 27155322 |
| both cd8+ and cd4+ t cells contribute to corneal clouding and viral clearance following vaccinia virus infection in c57bl/6 mice. | vaccinia virus (vacv) keratitis is a serious complication following smallpox vaccination and can lead to blindness. the pathological mechanisms involved in ocular vacv infection are poorly understood. previous studies have used rabbits, but the lack of immune reagents and transgenic or knockout animals makes them less suitable for mechanistic studies. we report that infection of c57bl/6 mice with 1 × 10(7) pfu of vaccinia virus strain wr results in blepharitis, corneal neovascularization, and st ... | 2016 | 27170749 |
| complete genome sequence of vaccinia virus strain l-ivp. | most of the live vaccine doses of vaccinia virus donated to the intensified smallpox eradication programme after 1971 were prepared using the l-ivp strain. a mixture of three clones of the l-ivp strain was sequenced using myseq. consensus sequence similarity with the vaccinia virus lister strain is 99.5%. | 2016 | 27174282 |
| impaired innate, humoral, and cellular immunity despite a take in smallpox vaccine recipients. | smallpox vaccine is highly effective, inducing protective immunity to smallpox and diseases caused by related orthopoxviruses. smallpox vaccine efficacy was historically defined by the appearance of a lesion or "take" at the vaccine site, which leaves behind a characteristic scar. both the take and scar are readily recognizable and were used during the eradication effort to indicate successful vaccination and to categorize individuals as "protected." however, the development of a typical vaccine ... | 2016 | 27177944 |
| identification of vaccine-altered circulating b cell phenotypes using mass cytometry and a two-step clustering analysis. | broadening our understanding of the abundance and phenotype of b cell subsets that are induced or perturbed by exogenous ags will improve the vaccine evaluation process. mass cytometry (cytof) is being used to increase the number of markers that can be investigated in single cells, and therefore characterize cell phenotype at an unprecedented level. we designed a panel of cytof abs to compare the b cell response in cynomolgus macaques at baseline, and 8 and 28 d after the second homologous immun ... | 2016 | 27183591 |
| nucleoside triphosphate phosphohydrolase i (nph i) functions as a 5' to 3' translocase in transcription termination of vaccinia early genes. | vaccinia virus early genes are transcribed immediately upon infection. nucleoside triphosphate phosphohydrolase i (nph i) is an essential component of the early gene transcription complex. nph i hydrolyzes atp to release transcripts during transcription termination. the atpase activity of nph i requires single-stranded (ss) dna as a cofactor; however, the source of this cofactor within the transcription complex is not known. based on available structures of transcription complexes it has been hy ... | 2016 | 27189950 |
| improved safety of a replication-competent poxvirus-based hiv vaccine with the introduction of the hsv-tk/gcv suicide gene system. | replication-competent vaccinia viruses (vacvs) show prolonged antigen expression time and greater stimulation of immune responses than their replication-incompetent counterparts. however, there is the potential risk of serious post-vaccination complications, especially for children and immunocompromised individuals, leading to safety concerns about the reintroduction of vacv as a vaccine vector. in this study, we improved the safety of the vaccinia virus tiantan (vacv-tt) based hiv vaccine by in ... | 2016 | 27195760 |
| phase 1 study of intravenous oncolytic poxvirus (vvdd) in patients with advanced solid cancers. | we have conducted a phase 1 study of intravenous vvdd, a western reserve strain oncolytic vaccinia virus, on 11 patients with standard treatment-refractory advanced colorectal or other solid cancers. the primary endpoints were maximum tolerated dose and associated toxicity while secondary endpoints were pharmacokinetics, pharmacodynamics, immune responses, and antitumor activity. no dose-limiting toxicities and treatment related severe adverse events were observed. the most common adverse events ... | 2016 | 27203445 |
| oncolytic vaccine virus harbouring the il-24 gene suppresses the growth of lung cancer by inducing apoptosis. | lung cancer has an especially high incidence rate worldwide, and its resistance to cell death and chemotherapeutic drugs increases its intractability. the vaccinia virus has been shown to destroy neoplasm within a short time and disseminate rapidly and extensively as an enveloped virion throughout the circulatory system, and this virus has also demonstrated a strong ability to overexpress exogenous genes. interleukin-24 (il-24/mda-7) is an important cytokine that belongs to the activating caspas ... | 2016 | 27208781 |
| use of reporter genes in the generation of vaccinia virus-derived vectors. | vaccinia virus (vacv) is one of the most extensively-studied viruses of the poxviridae family. it is easy to genetically modify, so it has become a key tool for many applications. in this context, reporter genes facilitate the study of the role of foreign genes introduced into the genome of vacv. in this review, we describe the type of reporter genes that have been used to generate reporter-expressing vacv and the applications of the recombinant viruses obtained. reporter-expressing vacv are cur ... | 2016 | 27213433 |
| povidone iodine ointment application to the vaccination site does not alter immunoglobulin g antibody response to smallpox vaccine. | u.s. military personnel deployed to high-risk areas receive the live vaccinia virus (vacv) smallpox vaccine acam2000. vacv shedding from the vaccination site can result in autoinoculation and contact transmission. we previously found that the application of povidone iodine ointment (pio) to the scarification site reduced viral shedding without altering the antibody response, as measured by plaque reduction neutralization or enzyme-linked immunosorbent assays. in this study, we used protein micro ... | 2016 | 27214505 |
| local antigen in nonlymphoid tissue promotes resident memory cd8+ t cell formation during viral infection. | tissue-resident memory (trm) cd8(+) t cells are functionally distinct from their circulating counterparts and are potent mediators of host protection against reinfection. whether local recognition of antigen in nonlymphoid tissues during infection can impact the formation of trm populations remains unresolved. using skin infections with vaccinia virus (vacv)-expressing model antigens, we found that local antigen recognition had a profound impact on trm formation. activated cd8(+) t cells traffic ... | 2016 | 27217536 |
| deletion of a44l, a46r and c12l vaccinia virus genes from the mva genome improved the vector immunogenicity by modifying the innate immune response generating enhanced and optimized specific t-cell responses. | mva is an attenuated vector that still retains immunomodulatory genes. we have previously reported its optimization after deleting the c12l gene, coding for the il-18 binding-protein. here, we analyzed the immunogenicity of mva vectors harboring the simultaneous deletion of a44l, related to steroid synthesis and a46r, a tlr-signaling inhibitor (mvaδa44l-a46r); or also including a deletion of c12l (mvaδc12l/δa44l-a46r). the absence of biological activities of the deleted genes in the mva vectors ... | 2016 | 27223301 |
| endemic orthopoxvirus circulating in procyonids in mexico. | limited serosurveillance studies suggested that orthopoxviruses (opxv) are widespread in the us (e.g., raccoonpox virus, skunkpox virus, volepox virus) and brazil (vaccinia virus); however, their animal reservoir(s) remain unconfirmed. mexican mammal diversity includes several species related to those in which evidence for opxv infections has been found (oryzomys, peromyscus, microtus, and procyonidae). the presence of these groups of mammals in mexico and the evidence of their possible involvem ... | 2016 | 27224209 |
| enhancement of anti-stlv-1/htlv-1 immune responses through multimodal effects of anti-ccr4 antibody. | human t-cell leukemia virus type 1 (htlv-1) causes adult t-cell leukemia and inflammatory diseases. because anti-htlv-1 immune responses are critical for suppressing infected cells, enhancing cellular immunity is beneficial for the treatment of htlv-1-associated diseases. using simian t-cell leukemia virus type 1 (stlv-1) infected japanese macaques, we analyzed the immune responses to viral antigens and the dynamics of virus-infected cells. the chemokine receptor ccr4 is expressed on stlv-1 infe ... | 2016 | 27250643 |
| construction of deletion-knockout mutant fowlpox virus (fwpv). | the construction of deletion-knockout poxviruses is a useful approach to determining the function of specific virus genes. this protocol is an adaptation of the transient dominant knockout selection protocol published by falkner and moss (1990) for use with vaccinia virus. the protocol makes use of the dominant selectable marker escherichia coli guanine phosphoribosyltransferase (gpt) gene (mulligan and berg, 1981), under the control of an early/late poxvirus promoter. the deletion viruses that ... | 2014 | 27257612 |
| the detection of vaccinia virus confirms the high circulation of orthopoxvirus in buffaloes living in geographical isolation, marajó island, brazilian amazon. | in brazil, serologic evidence of orthopoxvirus (opv) circulation showed positivity around 20% in cattle, humans, monkeys and rodents. although opv seropositivity has been described in buffalo herds in southeastern brazil, no vaccinia virus (vacv) (member of genus opv) outbreaks in buffalo herds have been described in this country. this study aimed to investigate the detection of anti-opv antibodies and to study the opv genome in brazilian buffalo herds. our results demonstrated a high opv seropo ... | 2016 | 27260805 |
| clonal redemption of autoantibodies by somatic hypermutation away from self-reactivity during human immunization. | clonal anergy is an enigmatic self-tolerance mechanism because no apparent purpose is served by retaining functionally silenced b cells bearing autoantibodies. human autoantibodies with ighv4-34*01 heavy chains bind to poly-n-acetyllactosamine carbohydrates (i/i antigen) on erythrocytes and b lymphocytes, cause cold agglutinin disease, and are carried by 5% of naive b cells that are anergic. we analyzed the specificity of three ighv4-34*01 igg antibodies isolated from healthy donors immunized ag ... | 2016 | 27298445 |
| infectio: a generic framework for computational simulation of virus transmission between cells. | viruses spread between cells, tissues, and organisms by cell-free and cell-cell mechanisms, depending on the cell type, the nature of the virus, or the phase of the infection cycle. the mode of viral transmission has a large impact on disease development, the outcome of antiviral therapies or the efficacy of gene therapy protocols. the transmission mode of viruses can be addressed in tissue culture systems using live-cell imaging. yet even in relatively simple cell cultures, the mechanisms of vi ... | 2017 | 27303704 |
| multiple bcl-2 family immunomodulators from vaccinia virus regulate mapk/ap-1 activation. | vaccinia virus (vacv) is a poxvirus and encodes many proteins that modify the host cell metabolism or inhibit the host response to infection. for instance, it is known that vacv infection can activate the mitogen-activated protein kinase (mapk)/activator protein 1 (ap-1) pathway and inhibit activation of the pro-inflammatory transcription factor nf-κb. since nf-κb and mapk/ap-1 share common upstream activators we investigated whether six different vacv bcl-2-like nf-κb inhibitors can also influe ... | 2016 | 27312213 |
| stress beyond translation: poxviruses and more. | poxviruses are large double-stranded dna viruses that form viral factories in the cytoplasm of host cells. these viruses encode their own transcription machinery, but rely on host translation for protein synthesis. thus, poxviruses have to cope with and, in most cases, reprogram host translation regulation. granule structures, called antiviral granules (avgs), have been observed surrounding poxvirus viral factories. avg formation is associated with abortive poxvirus infection, and avgs contain p ... | 2016 | 27314378 |
| opposing roles of double-stranded rna effector pathways and viral defense proteins revealed with crispr-cas9 knockout cell lines and vaccinia virus mutants. | vaccinia virus (vacv) decapping enzymes and cellular exoribonuclease xrn1 catalyze successive steps in mrna degradation and prevent double-stranded rna (dsrna) accumulation, whereas the viral e3 protein can bind dsrna. we showed that dsrna and e3 colocalized within cytoplasmic viral factories in cells infected with a decapping enzyme mutant as well as with wild-type vacv and that they coprecipitated with antibody. an e3 deletion mutant induced protein kinase r (pkr) and eukaryotic translation in ... | 2016 | 27334583 |
| recombinant sheep pox virus proteins elicit neutralizing antibodies. | the aim of this work was to evaluate the immunogenicity and neutralizing activity of sheep pox virus (sppv; genus capripoxvirus, family poxviridae) structural proteins as candidate subunit vaccines to control sheep pox disease. sppv structural proteins were identified by sequence homology with proteins of vaccinia virus (vacv) strain copenhagen. four sppv proteins (sppv-orf 060, sppv-orf 095, sppv-orf 117, and sppv-orf 122), orthologs of immunodominant l1, a4, a27, and a33 vacv proteins, respect ... | 2016 | 27338444 |
| genome sequence of vaccinia virus strain lister-butantan, a lister vaccine variant used during a smallpox eradication campaign in brazil. | here, we report the 187.8-kb genome sequence of vaccinia virus lister-butantan, which was used in brazil during the who smallpox eradication campaign. its genome showed an average similarity of 98.18% with the original lister isolate, highlighting the low divergence among related vaccinia virus vaccine strains, even after several passages in animals and cell culture. | 2016 | 27340056 |
| long-term safety of replication-defective smallpox vaccine (mva-bn) in atopic eczema and allergic rhinitis. | availability of a safe smallpox vaccine may be necessary under certain circumstances. use of the old life virus vaccine was associated with serious adverse events, particularly in the setting of atopic eczema (ae) and immunodeficiency. modified virus ankara (mva)-bn, a highly attenuated strain of vaccinia virus, was developed for vaccination with improved safety profile. | 2016 | 27357167 |
| a general method for rapid and cost-efficient large-scale production of 5' capped rna. | the eukaryotic mrna 5' cap structure is indispensible for pre-mrna processing, mrna export, translation initiation, and mrna stability. despite this importance, structural and biophysical studies that involve capped rna are challenging and rare due to the lack of a general method to prepare mrna in sufficient quantities. here, we show that the vaccinia capping enzyme can be used to produce capped rna in the amounts that are required for large-scale structural studies. we have therefore designed ... | 2016 | 27368341 |
| virusmapper: open-source nanoscale mapping of viral architecture through super-resolution microscopy. | the nanoscale molecular assembly of mammalian viruses during their infectious life cycle remains poorly understood. their small dimensions, generally bellow the 300nm diffraction limit of light microscopes, has limited most imaging studies to electron microscopy. the recent development of super-resolution (sr) light microscopy now allows the visualisation of viral structures at resolutions of tens of nanometers. in addition, these techniques provide the added benefit of molecular specific labell ... | 2016 | 27374400 |
| polymeric cups for cavitation-mediated delivery of oncolytic vaccinia virus. | oncolytic viruses (ov) could become the most powerful and selective cancer therapies. however, the limited transport of ov into and throughout tumors following intravenous injection means their clinical administration is often restricted to direct intratumoral dosing. application of physical stimuli, such as focused ultrasound, offers a means of achieving enhanced mass transport. in particular, shockwaves and microstreaming resulting from the instigation of an ultrasound-induced event known as i ... | 2016 | 27375160 |
| seroprevalence of orthopoxvirus in rural brazil: insights into anti-opv immunity status and its implications for emergent zoonotic opv. | bovine vaccinia (bv) is a zoonosis caused by vaccinia virus, a virus from orthopoxvirus genus (opv) that affects mainly cattle herds and humans in rural areas in brazil. because most studies have focused on outbreaks situations, data on bv epidemiology is limited. a cross sectional study in brazilian rural areas during 2012-2013 was conducted to determine the neutralizing antibodies seroprevalence and risk factors for bv. | 2016 | 27377374 |
| protein translation activity: a new measure of host immune cell activation. | we describe the in vivo ribopuromycylation (rpm) method, which uses a puromycin-specific ab to fluorescently label ribosome-bound puromycylated nascent chains, enabling measurement of translational activity via immunohistochemistry or flow cytometry. tissue staining provides a unique view of virus-induced activation of adaptive, innate, and stromal immune cells. rpm flow precisely quantitates virus-induced activation of lymphocytes and innate immune cells, and it provides a unique measure of imm ... | 2016 | 27385780 |
| membrane fusion during poxvirus entry. | poxviruses comprise a large family of enveloped dna viruses that infect vertebrates and invertebrates. poxviruses, unlike most dna viruses, replicate in the cytoplasm and encode enzymes and other proteins that enable entry, gene expression, genome replication, virion assembly and resistance to host defenses. entry of vaccinia virus, the prototype member of the family, can occur at the plasma membrane or following endocytosis. whereas many viruses encode one or two proteins for attachment and mem ... | 2016 | 27423915 |
| induction of heterologous tier 2 hiv-1-neutralizing and cross-reactive v1/v2-specific antibodies in rabbits by prime-boost immunization. | poxvirus prime-protein boost used in the rv144 trial remains the only immunization strategy shown to elicit a modest level of protection against hiv-1 acquisition in humans. although neutralizing antibodies (nab) were generated, they were against sensitive viruses, not the more resistant "tier 2" isolates that dominate circulating strains. instead, risk reduction correlated with antibodies recognizing epitopes in the v1/v2 region of hiv-1 envelope glycoprotein (env). here, we examined whether ti ... | 2016 | 27440894 |
| response of three different viruses to interferon priming and dithiothreitol treatment of avian cells. | we have previously shown that the replication of avian reovirus (arv) in chicken cells is much more resistant to interferon (ifn) than the replication of vesicular stomatitis virus (vsv) or vaccinia virus (vv). in this study, we have investigated the role that the double-stranded rna (dsrna)-activated protein kinase (pkr) plays in the sensitivity of these three viruses toward the antiviral action of chicken interferon. our data suggest that while interferon priming of avian cells blocks vaccinia ... | 2016 | 27440902 |
| oncolytic vaccinia virus inhibits human hepatocellular carcinoma mhcc97-h cell proliferation via endoplasmic reticulum stress, autophagy and wnt pathways. | hepatocellular carcinoma (hcc) is a highly lethal malignancy. vaccinia virus (vv) possessed many inherent advantages with respect to being engineered as a vector for cancer gene therapy, although the mechanism of action remains to be explored further. | 2016 | 27441866 |
| vaccinia virus dissemination requires p21-activated kinase 1. | the orthopoxvirus vaccinia virus (vacv) interacts with both actin and microtubule cytoskeletons in order to generate and spread progeny virions. here, we present evidence demonstrating the involvement of pak1 (p21-activated kinase 1) in the dissemination of vacv. although pak1 activation has previously been associated with optimal vacv entry via macropinocytosis, its absence does not affect the production of intracellular mature virions (imvs) and extracellular enveloped virions (eevs). our data ... | 2016 | 27465567 |
| retrograde transport from early endosomes to the trans-golgi network enables membrane wrapping and egress of vaccinia virus virions. | the anterograde pathway, from the endoplasmic reticulum through the trans-golgi network to the cell surface, is utilized by trans-membrane and secretory proteins. the retrograde pathway, which directs traffic in the opposite direction, is used following endocytosis of exogenous molecules and recycling of membrane proteins. microbes exploit both routes: viruses typically use the anterograde pathway for envelope formation prior to exiting the cell, whereas ricin and shiga-like toxins and some none ... | 2016 | 27466413 |
| virus-like particles displaying trimeric simian immunodeficiency virus (siv) envelope gp160 enhance the breadth of dna/modified vaccinia virus ankara siv vaccine-induced antibody responses in rhesus macaques. | the encouraging results of the rv144 vaccine trial have spurred interest in poxvirus prime-protein boost human immunodeficiency virus (hiv) vaccine modalities as a strategy to induce protective immunity. because vaccine-induced protective immunity is critically determined by hiv envelope (env) conformation, significant efforts are directed toward generating soluble trimeric env immunogens that assume native structures. using the simian immunodeficiency virus (siv)-macaque model, we tested the im ... | 2016 | 27466414 |
| monkeypox virus induces the synthesis of less dsrna than vaccinia virus, and is more resistant to the anti-poxvirus drug, ibt, than vaccinia virus. | monkeypox virus (mpxv) infection fails to activate the host anti-viral protein, pkr, despite lacking a full-length homologue of the vaccinia virus (vacv) pkr inhibitor, e3. since pkr can be activated by dsrna produced during a viral infection, we have analyzed the accumulation of dsrna in mpxv-infected cells. mpxv infection led to less accumulation of dsrna than vacv infection. because in vacv infections accumulation of abnormally low amounts of dsrna is associated with mutations that lead to re ... | 2016 | 27467578 |
| artificial ribonucleases inactivate a wide range of viruses using their ribonuclease, membranolytic, and chaotropic-like activities. | artificial ribonucleases (arnases) are small compounds catalysing rna cleavage. recently we demonstrated that arnases readily inactivate various viruses in vitro. here, for three series of arnases (1,4-diazabicyclo [2.2.2]octane-based and peptide-like compounds) we show that apart from ribonuclease activity the arnases display chaotropic-like and membranolytic activities. the levels of membranolytic and chaotropic-like activities correlate well with the efficiency of various viruses inactivation ... | 2016 | 27476043 |
| oncolytic virus therapy: a new era of cancer treatment at dawn. | oncolytic virus therapy is perhaps the next major breakthrough in cancer treatment following the success in immunotherapy using immune checkpoint inhibitors. oncolytic viruses are defined as genetically engineered or naturally occurring viruses that selectively replicate in and kill cancer cells without harming the normal tissues. t-vec (talimogene laherparepvec), a second-generation oncolytic herpes simplex virus type 1 (hsv-1) armed with gm-csf, was recently approved as the first oncolytic vir ... | 2016 | 27486853 |
| the ep152r orf of african swine fever virus strain georgia encodes for an essential gene that interacts with host protein bag6. | african swine fever virus (asfv) is the etiological agent of a contagious and often lethal disease of domestic pigs that has significant economic consequences for the swine industry. the viral genome encodes for more than 150 genes, and only a select few of these genes have been studied in some detail. here we report the characterization of open reading frame ep152r that has a predicted complement control module/scr domain. this domain is found in vaccinia virus proteins that are involved in blo ... | 2016 | 27497620 |
| live-vaccinia virus encapsulation in ph-sensitive polymer increases safety of a reservoir-targeted lyme disease vaccine by targeting gastrointestinal release. | the incidence of lyme disease has continued to rise despite attempts to control its spread. vaccination of zoonotic reservoirs of human pathogens has been successfully used to decrease the incidence of rabies in raccoons and foxes. we have previously reported on the efficacy of a vaccinia virus vectored vaccine to reduce carriage of borrelia burgdorferi in reservoir mice and ticks. one potential drawback to vaccinia virus vectored vaccines is the risk of accidental infection of humans. to reduce ... | 2016 | 27502570 |
| vaccinia virus k1 ankyrin repeat protein inhibits nf-κb activation by preventing rela acetylation. | the vaccinia virus (vacv) k1 protein inhibits dsrna-dependent protein kinase (pkr) activation. a consequence of this function is that k1 inhibits pkr-induced nf-κb activation during vacv infection. however, transient expression of k1 also inhibits toll-like receptor (tlr)-induced nf-κb activation. this suggests that k1 has a second nf-κb inhibitory mechanism that is pkr-independent. this possibility was explored by expressing k1 independently of infection and stimulating nf-κb under conditions t ... | 2016 | 27503790 |
| oncolytic virus therapy for cancer. | the use of oncolytic viruses to treat cancer is based on the selection of tropic tumor viruses or the generation of replication selective vectors that can either directly kill infected tumor cells or increase their susceptibility to cell death and apoptosis through additional exposure to radiation or chemotherapy. in addition, viral vectors can be modified to promote more potent tumor cell death, improve the toxicity profile, and/or generate host antitumor immunity. a variety of viruses have bee ... | 2013 | 27512656 |