Publications
| Title | Abstract | Year Filter | PMID(sorted ascending) Filter |
|---|
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| correction for eduardo-correia et al., isg15 is counteracted by vaccinia virus e3 protein and controls the proinflammatory response against viral infection. | 2016 | 27895186 | |
| 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 |
| notes from the field: adverse reaction after vaccinia virus vaccination - new mexico, 2016. | 2016 | 27906908 | |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| myxoma virus dsrna binding protein m029 inhibits the type i ifn-induced antiviral state in a highly species-specific fashion. | myxoma virus (myxv) is leporipoxvirus that possesses a specific rabbit-restricted host tropism but exhibits a much broader cellular host range in cultured cells. myxv is able to efficiently block all aspects of the type i interferon (ifn)-induced antiviral state in rabbit cells, partially in human cells and very poorly in mouse cells. the mechanism(s) of this species-specific inhibition of type i ifn-induced antiviral state is not well understood. here we demonstrate that myxv enc ... | 2017 | 28157174 |
| the vaccinia virus dna polymerase and its processivity factor. | vaccinia virus is the prototypic poxvirus. the 192 kilobase double-stranded dna viral genome encodes most if not all of the viral replication machinery. the vaccinia virus dna polymerase is encoded by the e9l gene. sequence analysis indicates that e9 is a member of the b family of replicative polymerases. the enzyme has both polymerase and 3'-5' exonuclease activities, both of which are essential to support viral replication. genetic analysis of e9 has identified residues and motifs whose altera ... | 2017 | 28159613 |
| treating tumors with a vaccinia virus expressing ifnβ illustrates the complex relationships between oncolytic ability and immunogenicity. | since previous work using a nonreplicating adenovirus-expressing mouse interferon-β (ad.mifnβ) showed promising preclinical activity, we postulated that a vector-expressing ifnβ at high levels that could also replicate would be even more beneficial. accordingly a replication competent, recombinant vaccinia viral vector-expressing mifnβ (vv.mifnβ) was tested. vv.mifnβ-induced antitumor responses in two syngeneic mouse flank models of lung cancer. although vv.mifnβ had equivalent in vivo efficacy ... | 2012 | 28160613 |
| chemotherapy enhances cd8(+) t cell-mediated antitumor immunity induced by vaccination with vaccinia virus. | the use of immunotherapy or chemotherapy alone is generally ineffective against well-established tumors. to overcome this intrinsic resistance against therapy for tumors, we have attempted to combine immunotherapy with chemotherapy. in this study, we tried to induce a rapid antitumor effect via chemoimmunotherapy using a vaccinia viral vaccine as an immunotherapeutic agent with anticancer agents including epigallocatechin-3-gallate (egcg) and conventional anticancer drugs. although a combination ... | 2007 | 28182877 |
| effects of mip-1α, mip-3α, and mip-3β on the induction of hiv gag-specific immune response with dna vaccines. | transfection of dna vaccines with chemokines may recruit dendritic cells (dcs) locally to capture the antigenic genes and their gene products to generate enhanced cd8(+) cytotoxic t lymphocytes (ctls). in this study, we investigated the effects of macrophage inflammatory protein (mip)-1α, mip-3α, and mip-3β on human immunodeficiency virus (hiv) gag dna vaccination. the chemokine plasmids markedly enhanced the local infiltration of inflammatory cells and increased the presence of cd11c(+) b7.2(+) ... | 2007 | 28182892 |
| 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 |
| identification and characterization of orf virus 050 protein proteolysis. | the orf virus 050 (orfv050) gene is located in the core region of the orfv genome. it is similar to vaccinia virus (vv) copenhagen l4r, and encodes the dna-binding virion core protein vp8, which has structures similar to the vv p25k core protein and may undergo similar proteolytic processing during virus assembly. three conserved ala-gly-x motifs at putative cleavage sites were identified in orfv050. to investigate the proteolysis of orfv050 and its participation in viral assembly, full-length a ... | 2017 | 28190135 |
| virus-specific cd8(+) t cells infiltrate melanoma lesions and retain function independently of pd-1 expression. | it is well known that cd8(+) tumor-infiltrating lymphocytes (tils) are correlated with positive prognoses in cancer patients and are used to determine the efficacy of immune therapies. although it is generally assumed that cd8(+) tils will be tumor-associated ag (taa) specific, it is unknown whether cd8(+) t cells with specificity for common pathogens also infiltrate tumors. if so, the presence of these t cells could alter the interpretation of prognostic and diagnostic til assays. we compared t ... | 2017 | 28202614 |
| establishing elements of a synthetic biology platform for vaccinia virus production: biobrick™ design, serum-free virus production and microcarrier-based cultivation of cv-1 cells. | vaccinia virus (vacv) is an established vector for vaccination and is beginning to prove effective as an oncolytic agent. industrial production of vacv stands to benefit in future from advances made by synthetic biology in genome engineering and standardisation. the cv-1 cell line can be used for vacv propagation and has been used extensively with the crispr/cas9 system for making precise edits of the vacv genome. here we take first steps toward establishing a scalable synthetic biology platform ... | 2017 | 28203643 |
| ac dielectrophoretic manipulation and electroporation of vaccinia virus using carbon nanoelectrode arrays. | this paper reports the capture and detection of vaccinia virus particles based on ac dielectrophoresis (dep) and electrochemical impedance measurements employing an embedded vertically aligned carbon nanofiber (vacnf) nanoelectrode array (nea) versus a macroscopic indium-tin-oxide (ito) transparent electrode in a "points-and-lid" configuration. the nano-dep device was fabricated by bonding two su-8 covered electrodes patterned using photolithography. the bottom electrode contains a 200 × 200 μm( ... | 2017 | 28211116 |
| 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 |
| 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 |
| the vaccinia virus k7 protein promotes histone methylation associated with heterochromatin formation. | it has been well established that many vaccinia virus proteins suppress host antiviral pathways by targeting the transcription of antiviral proteins, thus evading the host innate immune system. however, whether viral proteins have an effect on the host's overall cellular transcription is less understood. in this study we investigated the regulation of heterochromatin during vaccinia virus infection. heterochromatin is a highly condensed form of chromatin that is less transcriptionally active and ... | 2017 | 28257484 |
| antibody recognition of immunodominant vaccinia virus envelope proteins. | vaccinia virus (vacv) is an enveloped double stranded dna virus and the active ingredient of the smallpox vaccine. the systematic administration of this vaccine led to the eradication of circulating smallpox (variola virus, varv) from the human population. as a tribute to its success, global immunization was ended in the late 1970s. the efficacy of the vaccine is attributed to a robust production of protective antibodies against several envelope proteins of vacv, which cross-protect against infe ... | 2017 | 28271474 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| triad of human cellular proteins, irf2, fam111a, and rfc3, restrict replication of orthopoxvirus spi-1 host-range mutants. | viruses and their hosts can reach balanced states of evolution ensuring mutual survival, which makes it difficult to appreciate the underlying dynamics. to uncover hidden interactions, virus mutants that have lost defense genes may be used. deletion of the gene that encodes serine protease inhibitor 1 (spi-1) of rabbitpox virus and vaccinia virus, two closely related orthopoxviruses, prevents their efficient replication in human cells, whereas certain other mammalian cells remain fully permissiv ... | 2017 | 28320935 |
| detection and molecular characterization of zoonotic poxviruses circulating in the amazon region of colombia, 2014. | during 2014, cutaneous lesions were reported in dairy cattle and farmworkers in the amazon region of western colombia. samples from 6 patients were analyzed by serologic and pcr testing, and results demonstrated the presence of vaccinia virus and pseudocowpox virus. these findings highlight the need for increased poxvirus surveillance in colombia. | 2017 | 28322708 |
| current status of clinical trials assessing oncolytic virus therapy for urological cancers. | oncolytic virus therapy has recently been recognized as a promising new option for cancer treatment. oncolytic viruses replicate selectively in cancer cells, thus killing them without harming normal cells. notably, t-vec (talimogene laherparepvec, formerly called oncovex(gm)(-)(csf) ), an oncolytic herpes simplex virus type 1, was approved by the us food and drug administration for the treatment of inoperable melanoma in october 2015, and was subsequently approved in europe and australia in 2016 ... | 2017 | 28326624 |
| monkeypox virus host factor screen in haploid cells identifies essential role of garp complex in extracellular virus formation. | monkeypox virus (mpxv) is a human pathogen that is a member of the orthopoxvirus genus, which includes vaccinia virus and variola virus (the causative agent of smallpox). human monkeypox is considered an emerging zoonotic infectious disease. to identify host factors required for mpxv infection, we performed a genome-wide insertional mutagenesis screen in human haploid cells. the screen revealed several candidate genes, including those involved in golgi trafficking, glycosaminoglycan biosynthesis ... | 2017 | 28331092 |
| 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 |
| 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 |