Publications
| Title | Abstract | Year(sorted descending) Filter | PMID Filter |
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| cytosolic dna sensor-initiated innate immune responses in mouse ovarian granulosa cells. | viral infections of the ovary may perturb ovarian functions. however, the mechanisms underlying innate immune responses in the ovary are poorly understood. the present study demonstrates that cytosolic viral dna sensor signaling initiates the innate immune response in mouse ovarian granulosa cells and affects endocrine function. the cytosolic dna sensors p204 and cgas and their common signaling adaptor stimulator of interferon (ifn) genes (sting) were constitutively expressed in granulosa cells. ... | 2017 | 28351933 |
| rational combination of oncolytic vaccinia virus and pd-l1 blockade works synergistically to enhance therapeutic efficacy. | both anti-pd1/pd-l1 therapy and oncolytic virotherapy have demonstrated promise, yet have exhibited efficacy in only a small fraction of cancer patients. here we hypothesized that an oncolytic poxvirus would attract t cells into the tumour, and induce pd-l1 expression in cancer and immune cells, leading to more susceptible targets for anti-pd-l1 immunotherapy. our results demonstrate in colon and ovarian cancer models that an oncolytic vaccinia virus attracts effector t cells and induces pd-l1 e ... | 2017 | 28345650 |
| gastrointestinal microbiome dysbiosis in infant mice alters peripheral cd8(+) t cell receptor signaling. | we recently reported that maternal antibiotic treatment (mat) of mice in the last days of pregnancy and during lactation dramatically alters the density and composition of the gastrointestinal microbiota of their infants. mat infants also exhibited enhanced susceptibility to a systemic viral infection and altered adaptive immune cell activation phenotype and function. cd8(+) effector t cells from mat infants consistently demonstrate an inability to sustain interferon gamma (ifn-γ) production in ... | 2017 | 28337207 |
| dynamic monitoring of membrane nanotubes formation induced by vaccinia virus on a high throughput microfluidic chip. | membrane nanotubes (mnts) are physical connections for intercellular communication and induced by various viruses. however, the formation of vaccinia virus (vacv)-induced mnts has never been studied. in this report, vacv-induced mnts formation process was monitored on a microfluidic chip equipped with a series of side chambers, which protected mnts from fluidic shear stress. mnts were formed between susceptible cells and be facilitated by vacv infection through three patterns. the formed mnts va ... | 2017 | 28317863 |
| deletion of f4l (ribonucleotide reductase) in vaccinia virus produces a selective oncolytic virus and promotes anti-tumor immunity with superior safety in bladder cancer models. | bladder cancer has a recurrence rate of up to 80% and many patients require multiple treatments that often fail, eventually leading to disease progression. in particular, standard of care for high-grade disease, bacillus calmette-guérin (bcg), fails in 30% of patients. we have generated a novel oncolytic vaccinia virus (vacv) by mutating the f4l gene that encodes the virus homolog of the cell-cycle-regulated small subunit of ribonucleotide reductase (rrm2). the f4l-deleted vacvs are highly atten ... | 2017 | 28289079 |
| il-18-dependent nkg2d ligand upregulation on accessory cells is mediated by the pi3k/gsk-3 pathway. | nk cells are critical for the control of viral infections. studies have shown that efficient nk cell activation in response to infection with vv in vivo requires multiple pathways, including the nkg2d pathway. we have recently shown that il-18 is necessary for the activation of nk cells through upregulation of the nkg2d ligand rae-1 on dcs upon vv infection. however, how il-18r signaling on the accessory cells contributes to rae-1 up-regulation remains to be defined. in this study, we found il-1 ... | 2017 | 28283665 |
| rna-seq based transcriptome analysis of the type i interferon host response upon vaccinia virus infection of mouse cells. | vaccinia virus (vacv) encodes the soluble type i interferon (ifn) binding protein b18 that is secreted from infected cells and also attaches to the cell surface, as an immunomodulatory strategy to inhibit the host ifn response. by using next generation sequencing technologies, we performed a detailed rna-seq study to dissect at the transcriptional level the modulation of the ifn based host response by vacv and b18. transcriptome profiling of l929 cells after incubation with purified recombinant ... | 2017 | 28280747 |
| survival of tissue-resident memory t cells requires exogenous lipid uptake and metabolism. | tissue-resident memory t (trm) cells persist indefinitely in epithelial barrier tissues and protect the host against pathogens. however, the biological pathways that enable the long-term survival of trm cells are obscure. here we show that mouse cd8(+) trm cells generated by viral infection of the skin differentially express high levels of several molecules that mediate lipid uptake and intracellular transport, including fatty-acid-binding proteins 4 and 5 (fabp4 and fabp5). we further show that ... | 2017 | 28219080 |
| divergent roles of β- and γ-actin isoforms during spread of vaccinia virus. | actin is a major component of the cytoskeleton and is present as two isoforms in non-muscle cells: β- and γ-cytoplasmic actin. these isoforms are strikingly conserved, differing by only four n-terminal amino acids. during spread from infected cells, vaccinia virus (vacv) particles induce localized actin nucleation that propel virus to surrounding cells and facilitate cell-to-cell spread of infection. here we show that virus-tipped actin comets are composed of β- and γ-actin. we employed isoform- ... | 2017 | 28218453 |
| proteomic screen for cellular targets of the vaccinia virus f10 protein kinase reveals that phosphorylation of mdia regulates stress fiber formation. | vaccinia virus, a complex dsdna virus, is unusual in replicating exclusively within the cytoplasm of infected cells. although this prototypic poxvirus encodes >200 proteins utilized during infection, a significant role for host proteins and cellular architecture is increasingly evident. the viral b1 kinase and h1 phosphatase are known to target cellular proteins as well as viral substrates, but little is known about the cellular substrates of the f10 kinase. f10 is essential for virion morphogen ... | 2017 | 28183815 |
| investigating viruses during the transformation of molecular biology. | this reflections article describes my early work on viral enzymes and the discovery of mrna capping, how my training in medicine and biochemistry merged as i evolved into a virologist, the development of viruses as vaccine vectors, and how scientific and technological developments during the 1970s and beyond set the stage for the interrogation of nearly every step in the reproductive cycle of vaccinia virus (vacv), a large dna virus with about 200 genes. the reader may view this article as a wor ... | 2017 | 28154190 |
| entirely plasmid-based reverse genetics system for rotaviruses. | rotaviruses (rvs) are highly important pathogens that cause severe diarrhea among infants and young children worldwide. the understanding of the molecular mechanisms underlying rv replication and pathogenesis has been hampered by the lack of an entirely plasmid-based reverse genetics system. in this study, we describe the recovery of recombinant rvs entirely from cloned cdnas. the strategy requires coexpression of a small transmembrane protein that accelerates cell-to-cell fusion and vaccinia vi ... | 2017 | 28137864 |
| online size-exclusion and ion-exchange chromatography on a saxs beamline. | biological small angle x-ray scattering (biosaxs) is a powerful technique in molecular and structural biology used to determine solution structure, particle size and shape, and surface-to-volume ratio of macromolecules. the technique is applicable to a very wide variety of solution conditions spanning a broad range of concentrations, ph values, ionic strengths, temperatures, additives, etc., but the sample is required to be monodisperse. this caveat led to the implementation of liquid chromatogr ... | 2017 | 28117806 |
| detection of vaccinia virus in urban domestic cats, brazil. | we investigated possible vaccinia virus (vacv) in urban house cats in brazil. serum samples from 6 cats were positive for vacv by pcr, indicating likely vacv circulation among house cats in urban areas of brazil. this finding highlights the importance of epidemiologic surveillance to avoid outbreaks among urban human populations. | 2017 | 28098542 |
| concomitant helminth infection downmodulates the vaccinia virus-specific immune response and potentiates virus-associated pathology. | the aim of this work was to elucidate the immunopathological mechanisms of how helminths may influence the course of a viral infection, using a murine model. severe virulence, a relevant increase in the virus titres in the lung and a higher mortality rate were observed in ascaris and vaccinia virus (vacv) co-infected mice, compared with vacv mono-infected mice. immunopathological analysis suggested that the ablation of cd8(+) t cells, the marked reduction of circulating cd4(+) t cells producing ... | 2017 | 28003150 |
| coherent brightfield microscopy provides the spatiotemporal resolution to study early stage viral infection in live cells. | viral infection starts with a virus particle landing on a cell surface followed by penetration of the plasma membrane. due to the difficulty of measuring the rapid motion of small-sized virus particles on the membrane, little is known about how a virus particle reaches an endocytic site after landing at a random location. here, we use coherent brightfield (cobri) microscopy to investigate early stage viral infection with ultrahigh spatiotemporal resolution. by detecting intrinsic scattered light ... | 2017 | 28067508 |
| ribosome profiling reveals translational upregulation of cellular oxidative phosphorylation mrnas during vaccinia virus-induced host shutoff. | vaccinia virus infection causes a host shutoff that is marked by global inhibition of host protein synthesis. though the host shutoff may facilitate reallocation of cellular resources for viral replication and evasion of host antiviral immune responses, it poses a challenge for continuous synthesis of cellular proteins that are important for viral replication. it is, however, unclear whether and how certain cellular proteins may be selectively synthesized during the vaccinia virus-induced host s ... | 2017 | 28003488 |
| enhancing expression of functional human sodium iodide symporter and somatostatin receptor in recombinant oncolytic vaccinia virus for in vivo imaging of tumors. | oncolytic virus (ov) therapy has emerged as a novel tool in our therapeutic arsenals for fighting cancer. as a live biologic agent, ov has the ability to target and selectively amplify at the tumor sites. we have reported that a vaccinia-based ov (pexa-vec) has shown good efficacy in preclinical models and in clinical trials. to give an additional tool to clinicians to allow both treatment of the tumor and improved visualization of tumor margins, we developed new viral-based platforms with 2 spe ... | 2017 | 27635026 |
| 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 |
| 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 |
| molecular evidence of orthopoxvirus dna in capybara (hydrochoerus hydrochaeris) stool samples. | vaccinia virus (vacv) is responsible for outbreaks in brazil and has immense potential as an emerging virus. vacv can be found naturally circulating in india, pakistan and south america, where it causes infections characterised by exanthematic lesions in buffaloes, cattle and humans. the transmission cycle of brazilian vacv has still not been fully characterised; one of the most important gaps in knowledge being the role of wild animals. capybaras, which are restricted to the americas, are the w ... | 2017 | 27771792 |
| oncolytic virotherapy and gene therapy strategies for hepatobiliary cancers. | advanced liver cancers and biliary cancers represent diseases with dismal prognosis because of frequent local invasion and metastasis. effective therapeutic agents for these cancers have not been established. oncolytic viruses (ovs) constitute a novel class of promising, selective anticancer agents and recent studies have elucidated their unique features. moreover, clinical trials are demonstrating promising results. numerous ovs are being tested in preclinical models of hepatocellular carcinoma ... | 2017 | 28359239 |
| vaccinia virus a6 is a two-domain protein requiring a cognate n-terminal domain for full viral membrane assembly activity. | poxvirus virion biogenesis is a complex, multistep process, starting with the formation of crescent-shaped viral membranes, followed by their enclosure of viral core to form the spherical immature virions. crescent formation requires a group of proteins that are highly conserved among poxviruses, including a6 and a11 of vaccinia virus (vacv). to gain a better understanding of the molecular function of a6, we established a hela cell line that inducibly expressed vacv-a6, which allowed us to const ... | 2017 | 28275183 |
| identification and functional analysis of the gtpv bidirectional promoter region. | the goat pox chick embryo-attenuated virus (gtpv) has been developed as an effective vaccine that can elicit protective immune responses. it possesses a large genome and a robust ability to express exogenous genes. thus, this virus is an ideal vector for recombinant live vaccines for infectious diseases in ruminant animals. in this study, we identified a novel bidirectional promoter region of gtpv through screening named pbvv(±). pbvv(±) is located between etf-l and vitf-3, which are transcribed ... | 2017 | 27771746 |
| viruses as nanomedicine for cancer. | oncolytic virotherapy, a type of nanomedicine in which oncolytic viruses (ovs) are used to selectively infect and lyse cancer cells, is an emerging field in cancer therapy. some ovs exhibit a specific tropism for cancer cells, whereas others require genetic modification to enhance their binding with and entry into cancer cells. ovs both kill tumor cells and induce the host's immune response against tumor cells. armed with antitumor cellular molecules, antibodies, and/or in combination with antic ... | 2017 | 27703350 |
| npf motifs in the vaccinia virus protein a36 recruit intersectin-1 to promote cdc42:n-wasp-mediated viral release from infected cells. | during its egress, vaccinia virus transiently recruits ap-2 and clathrin after fusion with the plasma membrane. this recruitment polarizes the viral protein a36 beneath the virus, enhancing actin polymerization and the spread of infection. we now demonstrate that three npf motifs in the c-terminus of a36 recruit ap-2 and clathrin by interacting directly with the epsin15 homology domains of eps15 and intersectin-1. a36 is the first identified viral npf motif containing protein shown to interact w ... | 2016 | 27670116 |
| dok-1 and dok-2 regulate the formation of memory cd8+ t cells. | diverse signals received by cd8(+) t cells are integrated to achieve the required magnitude of cell expansion and the appropriate balance of effector/memory cd8(+) t cell generation. notably, the strength and nature of tcr signaling influence the differentiation and functional capacity of effector and memory cd8(+) t cells. dok-1 and dok-2, the two members of the dok family expressed in t cells, negatively regulate tcr signaling in vitro. however, the role of dok proteins in modulating t cell fu ... | 2016 | 27664281 |
| single-particle characterization of oncolytic vaccinia virus by flow virometry. | vaccinia virus (vv) is an oncolytic virus that is currently being evaluated as a promising cancer vaccine in several phase i, ii and iii clinical trials. although several quality control tests are performed on each new batch of virus, these do not routinely include a systematic characterization of virus particle homogeneity, or relate the infectious titer to the total number of submicron sized particles (ssps) present in the sample. ssps are comprised of infectious virus and non-infectious viral ... | 2016 | 27614781 |
| engineering of double recombinant vaccinia virus with enhanced oncolytic potential for solid tumor virotherapy. | vaccinia virus (vacv) oncolytic therapy has been successful in a number of tumor models. in this study our goal was to generate a double recombinant vaccinia virus (vv-gmcsf-lact) with enhanced antitumor activity that expresses exogenous proteins: the antitumor protein lactaptin and human granulocyte-macrophage colony-stimulating factor (gm-csf). lactaptin has previously been demonstrated to act as a tumor suppressor in mouse hepatoma as well as mda-mb-231 human adenocarcinoma cells grafted into ... | 2016 | 27708236 |
| 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 |
| vaccinia virus western reserve induces rapid surface expression of a host molecule detected by the antibody 4c7 that is distinct from clec2d. | in this study, the effect of active infection with vaccinia virus western reserve (vacv wr) on expression of c-type lectin domain family 2 (clec2d), a ligand of the human nk cell inhibitory receptor nkr-p1, was examined. as predicted, vacv infection led to a loss of clec2d mrna in 221 cells, a b cell lymphoma line. surprisingly, vacv infection of 221 cells caused a dramatic increase in cell surface staining for one clec2d-specific antibody, 4c7. there were no changes in other antibodies specific ... | 2016 | 27862195 |
| vectorization in an oncolytic vaccinia virus of an antibody, a fab and a scfv against programmed cell death -1 (pd-1) allows their intratumoral delivery and an improved tumor-growth inhibition. | we report here the successful vectorization of a hamster monoclonal igg (namely j43) recognizing the murine programmed cell death-1 (mpd-1) in western reserve (wr) oncolytic vaccinia virus. three forms of mpd-1 binders have been inserted into the virus: whole antibody (mab), fragment antigen-binding (fab) or single-chain variable fragment (scfv). mab, fab and scfv were produced and assembled with the expected patterns in supernatants of cells infected by the recombinant viruses. the three purifi ... | 2016 | 27853644 |
| vaccinia virus protein c6 inhibits type i ifn signalling in the nucleus and binds to the transactivation domain of stat2. | the type i interferon (ifn) response is a crucial innate immune signalling pathway required for defense against viral infection. accordingly, the great majority of mammalian viruses possess means to inhibit this important host immune response. here we show that vaccinia virus (vacv) strain western reserve protein c6, is a dual function protein that inhibits the cellular response to type i ifns in addition to its published function as an inhibitor of irf-3 activation, thereby restricting type i i ... | 2016 | 27907166 |
| thymic stromal lymphopoietin and il-33 promote skin inflammation and vaccinia virus replication in a mouse model of atopic dermatitis. | 2016 | 26830114 | |
| 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 |
| 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 |
| 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 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| erratum to: a novel vaccinia virus with dual oncolytic and anti-angiogenic therapeutic effects against triple-negative breast cancer. | 2016 | 27026359 | |
| 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 |
| 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 |
| 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 |
| 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 |
| a simple and efficient approach to construct mutant vaccinia virus vectors. | the crispr-associated endonuclease cas9 can edit particular genomic loci directed by a single guide rna (grna). the crispr/cas9 system has been successfully employed for editing genomes of various organisms. here we describe a protocol for editing the vaccinia virus (vv) genome in the cytoplasm of vv-infected cv-1 cells using the rna-guided cas9. rna-guided cas9 induces double-stranded dna breaks facilitating homologous recombination efficiently and specifically in the targeted site of vv and a ... | 2016 | 27842362 |
| 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 |
| 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 |
| 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 |
| 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 |
| expression of dai by an oncolytic vaccinia virus boosts the immunogenicity of the virus and enhances antitumor immunity. | in oncolytic virotherapy, the ability of the virus to activate the immune system is a key attribute with regard to long-term antitumor effects. vaccinia viruses bear one of the strongest oncolytic activities among all oncolytic viruses. however, its capacity for stimulation of antitumor immunity is not optimal, mainly due to its immunosuppressive nature. to overcome this problem, we developed an oncolytic vv that expresses intracellular pattern recognition receptor dna-dependent activator of ifn ... | 2016 | 27626058 |
| combined expression of mir-34a and smac mediated by oncolytic vaccinia virus synergistically promote anti-tumor effects in multiple myeloma. | despite great progress made in the treatment of multiple myeloma (mm), it is still incurable. promising phase ii clinical results have been reported recently for oncolytic vaccinia virus (ovv) clinic therapeutics. one reason for this has focused on the critical therapeutic importance of the immune response raised by these viruses. however, few studies have performed their applications as an optimal delivery system for therapeutic gene, especially mirna in mm. in this study, we constructed two no ... | 2016 | 27552933 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| oncolytic virus efficiency inhibited growth of tumour cells with multiple drug resistant phenotype in vivo and in vitro. | tumour resistance to a wide range of drugs (multiple drug resistant, mdr) acquired after intensive chemotherapy is considered to be the main obstacle of the curative treatment of cancer patients. recent work has shown that oncolytic viruses demonstrated prominent potential for effective treatment of diverse cancers. here, we evaluated whether genetically modified vaccinia virus (livp-gfp) may be effective in treatment of cancers displaying mdr phenotype. | 2016 | 27538520 |
| live-cell imaging of vaccinia virus recombination. | recombination between co-infecting poxviruses provides an important mechanism for generating the genetic diversity that underpins evolution. however, poxviruses replicate in membrane-bound cytoplasmic structures known as factories or virosomes. these are enclosed structures that could impede dna mixing between co-infecting viruses, and mixing would seem to be essential for this process. we hypothesize that virosome fusion events would be a prerequisite for recombination between co-infecting poxv ... | 2016 | 27525721 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| natural vaccinia virus infection: diagnosis, isolation, and characterization. | natural infections of vaccinia virus (vacv)-the prototype species of the orthopoxvirus genus, from the family poxviridae and subfamily chordopoxvirinae-cause an occupational emergent zoonotic disease that is primarily associated with the handling of infected dairy cattle. in humans, vacv infection is characterized by skin lesions, primarily on the hands, and accompanied by systemic symptoms such as fever, myalgia, headache, and lymphadenopathy. the diagnosis of vacv is usually performed accordin ... | 2016 | 27517335 |
| 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 |
| notes from the field: adverse reaction after vaccinia virus vaccination - new mexico, 2016. | 2016 | 27906908 | |
| oncolytic virotherapy for pediatric malignancies: future prospects. | pediatric solid tumors remain a major health concern, with nearly 16,000 children diagnosed each year. of those, ~2,000 succumb to their disease, and survivors often suffer from lifelong disability secondary to toxic effects of current treatments. countless multimodality treatment regimens are being explored to make advances against this deadly disease. one targeted treatment approach is oncolytic virotherapy. conditionally replicating viruses can infect tumor cells while leaving normal cells un ... | 2016 | 27579298 |
| colonization of xenograft tumors by oncolytic vaccinia virus (vacv) results in enhanced tumor killing due to the involvement of myeloid cells. | the mechanisms by which vaccinia virus (vacv) interacts with the innate immune components are complex and involve different mechanisms. inos-mediated no production by myeloid cells is one of the central antiviral mechanisms and this study aims to investigate specifically whether inos-mediated no production by myeloid cells, is involved in tumor eradication following the virus treatment. | 2016 | 27993141 |
| correction for eduardo-correia et al., isg15 is counteracted by vaccinia virus e3 protein and controls the proinflammatory response against viral infection. | 2016 | 27895186 | |
| oncolytic vaccinia virus combined with radiotherapy induces apoptotic cell death in sarcoma cells by down-regulating the inhibitors of apoptosis. | advanced extremity melanoma and sarcoma present a significant therapeutic challenge, requiring multimodality therapy to treat or even palliate disease. these aggressive tumours are relatively chemo-resistant, therefore new treatment approaches are urgently required. we have previously reported on the efficacy of oncolytic virotherapy (ov) delivered by isolated limb perfusion. in this report, we have improved therapeutic outcomes by combining ov with radiotherapy. in vitro, the combination of onc ... | 2016 | 27783991 |
| 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 |
| 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 |
| reprogramming antitumor immunity against chemoresistant ovarian cancer by a cxcr4 antagonist-armed viral oncotherapy. | ovarian cancer remains the most lethal gynecologic malignancy owing to late detection, intrinsic and acquired chemoresistance, and remarkable heterogeneity. here, we explored approaches to inhibit metastatic growth of murine and human ovarian tumor variants resistant to paclitaxel and carboplatin by oncolytic vaccinia virus expressing a cxcr4 antagonist to target the cxcl12 chemokine/cxcr4 receptor signaling axis alone or in combination with doxorubicin. the resistant variants exhibited augmente ... | 2016 | 28035333 |
| vector-based genetically modified vaccines: exploiting jenner's legacy. | the global vaccine market is diverse while facing a plethora of novel developments. genetic modification (gm) techniques facilitate the design of 'smarter' vaccines. for many of the major infectious diseases of humans, like aids and malaria, but also for most human neoplastic disorders, still no vaccines are available. it may be speculated that novel gm technologies will significantly contribute to their development. while a promising number of studies is conducted on gm vaccines and gm vaccine ... | 2016 | 28029542 |
| 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 |
| vaccinia virus immunomodulator a46: a lipid and protein-binding scaffold for sequestering host tir-domain proteins. | vaccinia virus interferes with early events of the activation pathway of the transcriptional factor nf-kb by binding to numerous host tir-domain containing adaptor proteins. we have previously determined the x-ray structure of the a46 c-terminal domain; however, the structure and function of the a46 n-terminal domain and its relationship to the c-terminal domain have remained unclear. here, we biophysically characterize residues 1-83 of the n-terminal domain of a46 and present the x-ray structur ... | 2016 | 27973613 |
| serro 2 virus highlights the fundamental genomic and biological features of a natural vaccinia virus infecting humans. | vaccinia virus (vacv) has been implicated in infections of dairy cattle and humans, and outbreaks have substantially impacted local economies and public health in brazil. during a 2005 outbreak, a vacv strain designated serro 2 virus (s2v) was collected from a 30-year old male milker. our aim was to phenotypically and genetically characterize this vacv brazilian isolate. s2v produced small round plaques without associated comets when grown in bsc40 cells. furthermore, s2v was less virulent than ... | 2016 | 27973399 |
| dual-specific chimeric antigen receptor t cells and an indirect vaccine eradicate a variety of large solid tumors in an immunocompetent, self-antigen setting. | purpose: while adoptive transfer of t cells bearing a chimeric antigen receptor (car) can eliminate substantial burdens of some leukemias, the ultimate challenge remains the eradication of large solid tumors for most cancers. we aimed to develop an immunotherapy approach effective against large tumors in an immunocompetent, self-antigen preclinical mouse model.experimental design: in this study, we generated dual-specific t cells expressing both a car specific for her2 and a tcr specific for the ... | 2016 | 27965307 |
| genomic identification of human vaccinia virus keratoconjunctivitis and its importance as a laboratory-acquired infection. | vaccinia virus (vacv) is a member of orthopoxvirus genus of the family poxviridae. vacvs are enveloped, double-stranded dna viruses. several species of this family, for example, molluscum contagiosum, smallpox, deerpox, horsepox, rabbitpox, and vacvs may cause conjunctivitis. | 2016 | 27958202 |
| 17(th) century variola virus reveals the recent history of smallpox. | smallpox holds a unique position in the history of medicine. it was the first disease for which a vaccine was developed and remains the only human disease eradicated by vaccination. although there have been claims of smallpox in egypt, india, and china dating back millennia [1-4], the timescale of emergence of the causative agent, variola virus (varv), and how it evolved in the context of increasingly widespread immunization, have proven controversial [4-9]. in particular, some molecular-clock-b ... | 2016 | 27939314 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| vaccinia virus uses retromer-independent cellular retrograde transport pathways to facilitate the wrapping of intracellular mature virions during viral morphogenesis. | poxviruses such as vaccinia virus (vacv) undertake a complex cytoplasmic replication cycle which involves morphogenesis through four distinct virion forms, and includes a crucial "wrapping" step whereby intracellular mature virions (imvs) are wrapped in two additional membranes to form intracellular enveloped virions (ievs). to determine if cellular retrograde transport pathways were required for this wrapping step we examined vacv morphogenesis in cells with reduced expression of the tetrameric ... | 2016 | 27581988 |
| vanilloid receptor 1 agonists, capsaicin and resiniferatoxin, enhance mhc class i-restricted viral antigen presentation in virus-infected dendritic cells. | dcs, like the sensory neurons, express vanilloid receptor 1 (vr1). here we demonstrate that the vr1 agonists, capsaicin (cp) and resiniferatoxin (rtx), enhance antiviral ctl responses by increasing mhc class i-restricted viral antigen presentation in dendritic cells (dcs). bone marrow-derived dcs (bm-dcs) were infected with a recombinant vaccinia virus (vv) expressing ova (vv-ova), and then treated with cp or rtx. both cp and rtx increased mhc class i-restricted presentation of virus-encoded end ... | 2016 | 27574502 |
| 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 |
| protein primary structure of the vaccinia virion at increased resolution | here we examine the protein covalent structure of the vaccinia virus virion. within two virion preparations, >88% of the theoretical vaccinia virus-encoded proteome was detected with high confidence, including the first detection of products from 27 open reading frames (orfs) previously designated "predicted," "uncharacterized," "inferred," or "hypothetical" polypeptides containing as few as 39 amino acids (aa) and six proteins whose detection required nontryptic proteolysis. we also detected th ... | 2016 | 27558425 |
| an in silico approach towards the identification of novel inhibitors of the tlr-4 signaling pathway. | precise functioning and fine-tuning of toll-like receptor 4 (tlr4) signaling is a critical requirement for the smooth functioning of the innate immune system, since aberrant tlr4 activation causes excessive production of pro-inflammatory cytokines and interferons. this can result in life threatening conditions such as septic shock and other inflammatory disorders. the trif-related adaptor molecule (tram) adaptor protein is unique to the tlr4 signaling pathway and abrogation of tram-mediated tlr4 ... | 2016 | 26264972 |
| microbiota is an essential element for mice to initiate a protective immunity against vaccinia virus. | the gastrointestinal tract of vertebrates harbors one of the most complex ecosystems known in microbial ecology and this indigenous microbiota almost always has a profound influence on host-parasite relationships, which can enhance or reduce the pathology of the infection. in this context, the impact of the microbiota during the infection of several viral groups remains poorly studied, including the family poxviridae. vaccinia virus (vacv) is a member of this family and is the causative agent of ... | 2016 | 26610433 |
| integration of linear and dendritic actin nucleation in nck-induced actin comets. | the nck adaptor protein recruits cytosolic effectors such as n-wasp that induce localized actin polymerization. experimental aggregation of nck sh3 domains at the membrane induces actin comet tails--dynamic, elongated filamentous actin structures similar to those that drive the movement of microbial pathogens such as vaccinia virus. here we show that experimental manipulation of the balance between unbranched/branched nucleation altered the morphology and dynamics of nck-induced actin comets. in ... | 2016 | 26609071 |
| 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 |
| 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 |
| 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 |
| 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 |