Publications
| Title | Abstract | Year Filter | PMID(sorted descending) Filter |
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| induction and analysis of bronchus-associated lymphoid tissue. | bronchus-associated lymphoid tissue (balt) forms spontaneously in the lung after pulmonary infection and has been identified as a highly organized lymphoid structure supporting the efficient priming of t cells in the lung. to explore the mechanisms and instructive signals controlling balt neogenesis we used both, a single dose of vaccinia virus mva and repeated inhalations of heat-inactivated pseudomonas aeruginosa (p. aeruginosa). intranasal administration of both pathogens induces highly organ ... | 2017 | 28063045 |
| modified vaccinia virus ankara: history, value in basic research, and current perspectives for vaccine development. | safety tested modified vaccinia virus ankara (mva) is licensed as third-generation vaccine against smallpox and serves as a potent vector system for development of new candidate vaccines against infectious diseases and cancer. historically, mva was developed by serial tissue culture passage in primary chicken cells of vaccinia virus strain ankara, and clinically used to avoid the undesirable side effects of conventional smallpox vaccination. adapted to growth in avian cells mva lost the ability ... | 2017 | 28057259 |
| humoral immunity to primary smallpox vaccination: impact of childhood versus adult immunization on vaccinia vector vaccine development in military populations. | modified vaccinia virus has been shown to be a safe and immunogenic vector platform for delivery of hiv vaccines. use of this vector is of particular importance to the military, with the implementation of a large scale smallpox vaccination campaign in 2002 in active duty and key civilian personnel in response to potential bioterrorist activities. humoral immunity to smallpox vaccination was previously shown to be long lasting (up to 75 years) and protective. however, using vaccinia-vectored vacc ... | 2017 | 28046039 |
| 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 |
| viral vector vaccines protect cockatiels from inflammatory lesions after heterologous parrot bornavirus 2 challenge infection. | avian bornaviruses are causative agents of proventricular dilatation disease (pdd), a chronic neurologic and often fatal disorder of psittacines including endangered species. to date no causative therapy or immunoprophylaxis is available. our previous work has shown that viral vector vaccines can delay the course of homologous bornavirus challenge infections but failed to protect against pdd when persistent infection was not prevented. the goal of this study was to refine our avian bornavirus va ... | 2017 | 28017426 |
| 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 |
| chronic type i ifn is sufficient to promote immunosuppression through accumulation of myeloid-derived suppressor cells. | failure of the immune system to eradicate viruses results in chronic viral infections, which are associated with increased susceptibility to secondary infections. pathogenic hiv or lymphocytic choriomeningitis virus chronic infections display a persistent type i ifn signature. in chronic lymphocytic choriomeningitis virus infection, blockade of type i ifn signaling partially restores antiviral responses. in a mouse model, we tested whether chronic administration of type i ifn, at doses mimicking ... | 2017 | 28003378 |
| 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 |
| 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 |
| a novel anti-viral role for stat3 in ifn-α signalling responses. | the cytokine, interferon (ifn)-α, induces a wide spectrum of anti-viral mediators, via the janus kinase/signal transducer and activator of transcription (jak/stat) pathway. stat1 and stat2 are well characterised to upregulate ifn-stimulated gene (isg) expression; but even though stat3 is also activated by ifn-α, its role in anti-viral isg induction is unclear. several viruses, including hepatitis c and mumps, reduce cellular stat3 protein levels, via the promotion of ubiquitin-mediated proteasom ... | 2017 | 27988795 |
| 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 |
| rapid and sensitive point-of-care detection of orthopoxviruses by abicap immunofiltration. | the rapid and reliable detection of infectious agents is one of the most challenging tasks in scenarios lacking well-equipped laboratory infrastructure, like diagnostics in rural areas of developing countries. commercially available point-of-care diagnostic tests for emerging and rare diseases are particularly scarce. | 2016 | 27938377 |
| emergence of a viral rna polymerase variant during gene copy number amplification promotes rapid evolution of vaccinia virus. | viruses are under relentless selective pressure from host immune defenses. to study how poxviruses adapt to innate immune detection pathways, we performed serial vaccinia virus infections in primary human cells. independent courses of experimental evolution with a recombinant strain lacking e3l revealed several high-frequency point mutations in conserved poxvirus genes, suggesting important roles for essential poxvirus proteins in innate immune subversion. two distinct mutations were identified ... | 2017 | 27928012 |
| 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 |
| notes from the field: adverse reaction after vaccinia virus vaccination - new mexico, 2016. | 2016 | 27906908 | |
| genetic variability of myxoma virus genomes. | myxomatosis is a recurrent problem on rabbit farms throughout europe despite the success of vaccines. to identify gene variations of field and vaccine strains that may be responsible for changes in virulence, immunomodulation, and immunoprotection, the genomes of 6 myxoma virus (myxv) strains were sequenced: german field isolates munich-1, fli-h, 2604, and 3207; vaccine strain mav; and challenge strain za. the analyzed genomes ranged from 147.6 kb (strain mav) to 161.8 kb (strain 3207). all sequ ... | 2017 | 27903800 |
| correction for eduardo-correia et al., isg15 is counteracted by vaccinia virus e3 protein and controls the proinflammatory response against viral infection. | 2016 | 27895186 | |
| ox40 cooperates with icos to amplify follicular th cell development and germinal center reactions during infection. | cognate interactions between t follicular helper (tfh) cells and b cells are essential for promoting protective ab responses. whereas costimulatory receptors such as icos are accepted as being important for the induction of tfh cell fate decision, other molecules may play key roles in amplifying or maintaining the tfh phenotype. in this study, with vaccinia virus infection in mice, we show that ox40 was expressed on tfh cells that accumulated at the t/b borders in the white pulp of the spleen an ... | 2017 | 27895177 |
| sensitization with vaccinia virus encoding h5n1 hemagglutinin restores immune potential against h5n1 influenza virus. | h5n1 highly pathogenic avian influenza (h5n1 hpai) virus causes elevated mortality compared with seasonal influenza viruses like h1n1 pandemic influenza (h1n1 pdm) virus. we identified a mechanism associated with the severe symptoms seen with h5n1 hpai virus infection. h5n1 hpai virus infection induced a decrease of dendritic cell number in the splenic extrafollicular t-cell zone and impaired formation of the outer layers of b-cell follicles, resulting in insufficient levels of antibody producti ... | 2016 | 27892498 |
| immune signatures of protective spleen memory cd8 t cells. | memory cd8 t lymphocyte populations are remarkably heterogeneous and differ in their ability to protect the host. in order to identify the whole range of qualities uniquely associated with protective memory cells we compared the gene expression signatures of two qualities of memory cd8 t cells sharing the same antigenic-specificity: protective (influenza-induced, flu-tm) and non-protective (peptide-induced, tim) spleen memory cd8 t cells. although flu-tm and tim express classical phenotypic memo ... | 2016 | 27883012 |
| daily ingestion of the probiotic lactobacillus paracasei st11 decreases vaccinia virus dissemination and lethality in a mouse model. | vaccinia virus (vacv) is an important pathogen. although studies have shown relationships between probiotics and viruses, the effect of probiotics on vacv infection is unknown. therefore, this work aims to investigate the probiotics effects on vacv infection. mice were divided into four groups, two non-infected groups, one receiving the probiotic, the other one not receiving it, and two groups infected intranasally with vacv western reserve (vacv-wr) receiving or not receiving the probiotic. vir ... | 2017 | 27873547 |
| detection of vaccinia virus in dairy cattle serum samples from 2009, uruguay. | we detected orthopoxvirus in 28 of 125 serum samples collected during 2009 from cattle in uruguay. two samples were pcr-positive for vaccinia virus and had sequences similar to those for vaccinia virus associated with outbreaks in brazil. autochthonous circulation of vaccinia virus in uruguay and other south american countries cannot be ruled out. | 2016 | 27869601 |
| occurrence of pseudocowpox virus associated to bovine viral diarrhea virus-1, brazilian amazon. | in 2011, an outbreak of severe vesicular disease occurred in the state of pará, amazon region. besides proliferative or verrucous lesions, cattle showed atypical clinical signs such as diarrhea and leading to death. the animals were submitted to clinical, pathological and molecular diagnosis, and laboratory tests have confirmed the presence of pseudocowpox virus (pcpv), a parapoxvirus genus member, and have also found bovine viral diarrhea virus-1 (bvdv-1), probably causing persistent infection. ... | 2016 | 27865267 |
| 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 |
| virus inactivation under the photodynamic effect of phthalocyanine zinc(ii) complexes. | various metal phthalocyanines have been studied for their capacity for photodynamic effects on viruses. two newly synthesized water-soluble phthalocyanine zn(ii) complexes with different charges, cationic methylpyridyloxy-substituted zn(ii)- phthalocyanine (znpcme) and anionic sulfophenoxy-substituted zn(ii)-phthalocyanine (znpcs), were used for photoinactivation of two dna-containing enveloped viruses (herpes simplex virus type 1 and vaccinia virus), two rna-containing enveloped viruses (bovine ... | 2017 | 27845890 |
| 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 |
| a conserved tripeptide sequence at the c terminus of the poxvirus dna processivity factor d4 is essential for protein integrity and function. | vaccinia virus (vacv) is a poxvirus, and the vacv d4 protein serves both as a uracil-dna glycosylase and as an essential component required for processive dna synthesis. the vacv a20 protein has no known catalytic function itself but associates with d4 to form the d4-a20 heterodimer that functions as the poxvirus dna processivity factor. the heterodimer enables the dna polymerase to efficiently synthesize extended strands of dna. upon characterizing the interaction between d4 and a20, we observe ... | 2016 | 27836975 |
| viral vector vaccines expressing nucleoprotein and phosphoprotein genes of avian bornaviruses ameliorate homologous challenge infections in cockatiels and common canaries. | avian bornaviruses are causative agents of proventricular dilatation disease (pdd), an often fatal disease of parrots and related species (order psittaciformes) which is widely distributed in captive psittacine populations and may affect endangered species. here, we established a vaccination strategy employing two different well described viral vectors, namely recombinant newcastle disease virus (ndv) and modified vaccinia virus ankara (mva) that were engineered to express the phosphoprotein and ... | 2016 | 27830736 |
| local action with global impact: highly similar infection patterns of human viruses and bacteriophages. | the investigation of host-pathogen interaction interfaces and their constituent factors is crucial for our understanding of an organism's pathogenesis. here, we explored the interactomes of hiv, hepatitis c virus, influenza a virus, human papillomavirus, herpes simplex virus, and vaccinia virus in a human host by analyzing the combined sets of virus targets and human genes that are required for viral infection. we also considered targets and required genes of bacteriophages lambda and t7 infecti ... | 2017 | 27822522 |
| heterologous immunity and persistent murine cytomegalovirus infection. | one's history of infections can affect the immune response to unrelated pathogens and influence disease outcome through the process of heterologous immunity. this can occur after acute viral infections, such as infections with lymphocytic choriomeningitis virus (lcmv) and vaccinia virus, where the pathogens are cleared, but it becomes a more complex issue in the context of persistent infections. in this study, murine cytomegalovirus (mcmv) was used as a persistent infection model to study hetero ... | 2017 | 27807227 |
| a multiplex pcr for viruses associated with exanthematic and vesicular disease in cattle. | exanthematic and papulo-vesicular lesions in the udder and teats of milking cows are fairly common in some brazilian dairies, especially those with poor sanitary conditions and hand milking. the orthopoxvirus vaccinia virus (vacv) and the parapoxviruses pseudocowpox virus (pcpv) and bovine popular stomatitis virus (bpsv) have been frequently associated with such conditions. elsewhere, bovine herpesvirus 2 (bohv-2) has also been associated with similar clinical signs. thus, we herein describe a c ... | 2017 | 27793645 |
| 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 |
| 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 |
| 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 |
| histone h2b-ifi16 recognition of nuclear herpesviral genome induces cytoplasmic interferon-β responses. | ifi16 (gamma-interferon-inducible protein 16), a predominantly nuclear protein involved in transcriptional regulation, also functions as an innate immune response dna sensor and induces the il-1β and antiviral type-1 interferon-β (ifn-β) cytokines. we have shown that ifi16, in association with brca1, functions as a sequence independent nuclear sensor of episomal dsdna genomes of kshv, ebv and hsv-1. recognition of these herpesvirus genomes resulted in ifi16 acetylation, brca1-ifi16-asc-procaspas ... | 2016 | 27764250 |
| mva vaccine encoding cmv antigens safely induces durable expansion of cmv-specific t cells in healthy adults. | attenuated poxvirus modified vaccinia ankara (mva) is a useful viral-based vaccine for clinical investigation, because of its excellent safety profile and property of inducing potent immune responses against recombinant (r) antigens. we developed triplex by constructing an rmva encoding 3 immunodominant cytomegalovirus (cmv) antigens, which stimulates a host antiviral response: ul83 (pp65), ul123 (ie1-exon4), and ul122 (ie2-exon5). we completed the first clinical evaluation of the triplex vaccin ... | 2017 | 27760761 |
| 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 |
| 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 |
| elements in the development of a production process for modified vaccinia virus ankara. | the production of several viral vaccines depends on chicken embryo fibroblasts or embryonated chicken eggs. to replace this logistically demanding substrate, we created continuous anatine suspension cell lines (cr and cr.pix), developed chemically-defined media, and established production processes for different vaccine viruses. one of the processes investigated in greater detail was developed for modified vaccinia virus ankara (mva). mva is highly attenuated for human recipients and an efficien ... | 2013 | 27694766 |
| poxvirus uracil-dna glycosylase-an unusual member of the family i uracil-dna glycosylases. | uracil-dna glycosylases are ubiquitous enzymes, which play a key role repairing damages in dna and in maintaining genomic integrity by catalyzing the first step in the base excision repair pathway. within the superfamily of uracil-dna glycosylases family i enzymes or ungs are specific for recognizing and removing uracil from dna. these enzymes feature conserved structural folds, active site residues and use common motifs for dna binding, uracil recognition and catalysis. within this family the e ... | 2016 | 27684934 |
| 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 |
| retinaldehyde dehydrogenase 2 as a molecular adjuvant for enhancement of mucosal immunity during dna vaccination. | in order for vaccines to induce efficacious immune responses against mucosally transmitted pathogens, such as hiv-1, activated lymphocytes must efficiently migrate to and enter targeted mucosal sites. we have previously shown that all-trans retinoic acid (atra) can be used as a vaccine adjuvant to enhance mucosal cd8(+) t cell responses during vaccination and improve protection against mucosal viral challenge. however, the atra formulation is incompatible with most recombinant vaccines, and the ... | 2016 | 27670072 |
| 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 |
| the primary immune response to vaccinia virus vaccination includes cells with a distinct cytotoxic effector cd4 t-cell phenotype. | smallpox was eradicated by a global program of inoculation with vaccinia virus (vv). robust vv-specific cd4 t-cell responses during primary infection are likely essential to controlling vv replication. although there is increasing interest in cytolytic cd4 t-cells across many viral infections, the importance of these cells during acute vv infection is unclear. | 2016 | 27639281 |
| protection of mice against the highly pathogenic vvihd-j by dna and fowlpox recombinant vaccines, administered by electroporation and intranasal routes, correlates with serum neutralizing activity. | the control of smallpox was achieved using live vaccinia virus (vv) vaccine, which successfully eradicated the disease worldwide. as the variola virus no longer exists as a natural infection agent, mass vaccination was discontinued after 1980. however, emergence of smallpox outbreaks caused by accidental or deliberate release of variola virus has stimulated new research for second-generation vaccine development based on attenuated vv strains. considering the closely related animal poxviruses tha ... | 2016 | 27637905 |
| 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 |
| 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 |
| 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 |
| structural analysis of point mutations at the vaccinia virus a20/d4 interface. | the vaccinia virus polymerase holoenzyme is composed of three subunits: e9, the catalytic dna polymerase subunit; d4, a uracil-dna glycosylase; and a20, a protein with no known enzymatic activity. the d4/a20 heterodimer is the dna polymerase cofactor, the function of which is essential for processive dna synthesis. the recent crystal structure of d4 bound to the first 50 amino acids of a20 (d4/a201-50) revealed the importance of three residues, forming a cation-π interaction at the dimerization ... | 2016 | 27599859 |
| the diverse family of arp2/3 complexes. | the arp2/3 complex has so far been considered to be a single seven-subunit protein complex required for actin nucleation and actin filament polymerization in diverse critical cellular functions including phagocytosis, vesicular trafficking and lamellipodia extension. the arp2/3 complex is also exploited by bacterial pathogens and viruses during cellular infectious processes. recent studies suggest that some subunits of the complex are dispensable in specific cellular contexts, pointing to the ex ... | 2017 | 27595492 |
| 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 |
| 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 |
| high-throughput screening to enhance oncolytic virus immunotherapy. | high-throughput screens can rapidly scan and capture large amounts of information across multiple biological parameters. although many screens have been designed to uncover potential new therapeutic targets capable of crippling viruses that cause disease, there have been relatively few directed at improving the efficacy of viruses that are used to treat disease. oncolytic viruses (ovs) are biotherapeutic agents with an inherent specificity for treating malignant disease. certain ov platforms - i ... | 2016 | 27579293 |
| 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 |
| 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 |
| 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 |
| increased attenuation but decreased immunogenicity by deletion of multiple vaccinia virus immunomodulators. | vaccinia virus (vacv)-derived vectors are popular candidates for vaccination against diseases such as hiv-1, malaria and tuberculosis. however, their genomes encode a multitude of proteins with immunomodulatory functions, several of which reduce the immunogenicity of these vectors. hitherto only limited studies have investigated whether the removal of these immunomodulatory genes in combination can increase vaccine efficacy further. to this end we constructed viruses based on vacv strain western ... | 2016 | 27544585 |
| 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 |
| 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 |
| novel therapeutic strategies in human malignancy: combining immunotherapy and oncolytic virotherapy. | results from randomized clinical trials over the last several years have finally begun to demonstrate the potential of oncolytic viral therapies to treat a variety of cancers. one reason for these successes has been the realization that this platform is most effective when considered primarily as an immunotherapy. cancer immunotherapy has also made dramatic strides recently with antibodies capable of blocking immune checkpoint inhibitors and adoptive t-cell therapies, notably car t-cells, leadin ... | 2015 | 27512672 |
| promising oncolytic agents for metastatic breast cancer treatment. | new therapies for metastatic breast cancer patients are urgently needed. the long-term survival rates remain unacceptably low for patients with recurrent disease or disseminated metastases. in addition, existing therapies often cause a variety of debilitating side effects that severely impact quality of life. oncolytic viruses constitute a developing therapeutic modality in which interest continues to build due to their ability to spare normal tissue while selectively destroying tumor cells. a n ... | 2015 | 27512671 |
| the emerging therapeutic potential of the oncolytic immunotherapeutic pexa-vec (jx-594). | oncolytic immunotherapeutics (ois) are viruses designed to preferentially replicate in and lyse cancer cells, thereby triggering antitumor immunity. numerous oncolytic platforms are currently in clinical development. here we review preclinical and clinical experience with pexa-vec (pexastimogene devacirepvec, jx-594). pexa-vec is derived from a vaccinia vaccine strain that has been engineered to target cancer cells and express the therapeutic transgene granulocyte macrophage colony-stimulating f ... | 2015 | 27512667 |
| the ex vivo purge of cancer cells using oncolytic viruses: recent advances and clinical implications. | hematological malignancies are treated with intensive high-dose chemotherapy, with or without radiation. this is followed by hematopoietic stem cell (hsc) transplantation (hsct) to rescue or reconstitute hematopoiesis damaged by the anticancer therapy. autologous hsc grafts may contain cancer cells and purging could further improve treatment outcomes. similarly, allogeneic hsct may be improved by selectively purging alloreactive effector cells from the graft rather than wholesale immune cell dep ... | 2015 | 27512666 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |