| plaque2.0-a high-throughput analysis framework to score virus-cell transmission and clonal cell expansion. | classical plaque assay measures the propagation of infectious agents across a monolayer of cells. it is dependent on cell lysis, and limited by user-specific settings and low throughput. here, we developed plaque2.0, a broadly applicable, fluorescence microscopy-based high-throughput method to mine patho-biological clonal cell features. plaque2.0 is an open source framework to extract information from chemically fixed cells by immuno-histochemistry or rna in situ hybridization, or from live cell ... | 2015 | 26413745 |
| new role of interleukin-10 in enhancing the antitumor efficacy of oncolytic vaccinia virus for treatment of pancreatic cancer. | although the profile of safety of tumor-targeted oncolytic virus (tov) is encouraging, the antitumor efficacy of tov alone is disappointing. interleukin-10 (il-10) plays an important role in carcinogenesis and anti-virus immunity. here we report that tumor-targeted oncolytic vaccinia virus (vv) armed with il10 shows promising potential for treatment of pancreatic cancer (paca). | 2015 | 26405610 |
| efficient reprogramming of human fibroblasts and blood-derived endothelial progenitor cells using nonmodified rna for reprogramming and immune evasion. | mrna reprogramming results in the generation of genetically stable induced pluripotent stem (ips) cells while avoiding the risks of genomic integration. previously published mrna reprogramming protocols have proven to be inconsistent and time-consuming and mainly restricted to fibroblasts, thereby demonstrating the need for a simple but reproducible protocol applicable to various cell types. so far there have been no published reports using mrna to reprogram any cell type derived from human bloo ... | 2015 | 26381596 |
| inhibition of translation initiation by protein 169: a vaccinia virus strategy to suppress innate and adaptive immunity and alter virus virulence. | vaccinia virus (vacv) is the prototypic orthopoxvirus and the vaccine used to eradicate smallpox. here we show that vacv strain western reserve protein 169 is a cytoplasmic polypeptide expressed early during infection that is excluded from virus factories and inhibits the initiation of cap-dependent and cap-independent translation. ectopic expression of protein 169 causes the accumulation of 80s ribosomes, a reduction of polysomes, and inhibition of protein expression deriving from activation of ... | 2015 | 26334635 |
| cloak and dagger: alternative immune evasion and modulation strategies of poxviruses. | as all viruses rely on cellular factors throughout their replication cycle, to be successful they must evolve strategies to evade and/or manipulate the defence mechanisms employed by the host cell. in addition to their expression of a wide array of host modulatory factors, several recent studies have suggested that poxviruses may have evolved unique mechanisms to shunt or evade host detection. these potential mechanisms include mimicry of apoptotic bodies by mature virions (mvs), the use of vira ... | 2015 | 26308043 |
| redundancy complicates the definition of essential genes for vaccinia virus. | vaccinia virus (vacv) genes are characterized as either essential or non-essential for growth in culture. it seems intuitively obvious that if a gene can be deleted without imparting a growth defect in vitro it does not have a function related to basic replication or spread. however, this interpretation relies on the untested assumption that there is no redundancy across the genes that have roles in growth in cell culture. first, we provide a comprehensive summary of the literature that describe ... | 2015 | 26290187 |
| mapping vaccinia virus dna replication origins at nucleotide level by deep sequencing. | poxviruses reproduce in the host cytoplasm and encode most or all of the enzymes and factors needed for expression and synthesis of their double-stranded dna genomes. nevertheless, the mode of poxvirus dna replication and the nature and location of the replication origins remain unknown. a current but unsubstantiated model posits only leading strand synthesis starting at a nick near one covalently closed end of the genome and continuing around the other end to generate a concatemer that is subse ... | 2015 | 26286988 |
| the role of vaccinia termination factor and cis-acting elements in vaccinia virus early gene transcription termination. | vaccinia virus early gene transcription termination requires the virion form of the viral rna polymerase (vrnap), nucleoside triphosphate phosphohydrolase i (nphi), atp, the vaccinia termination factor (vtf), and a u5nu termination signal in the nascent transcript. vtf, also the viral mrna capping enzyme, binds u5nu, and nphi hydrolyzes atp to release the transcript. nphi can release transcripts independent of vtf and u5nu if vrnap is not actively elongating. however, vtf and u5nu are required f ... | 2015 | 26280468 |
| an in silico approach towards the identification of novel inhibitors of the tlr-4 signaling pathway. | precise functioning and fine-tuning of toll-like receptor 4 (tlr4) signaling is a critical requirement for the smooth functioning of the innate immune system, since aberrant tlr4 activation causes excessive production of pro-inflammatory cytokines and interferons. this can result in life threatening conditions such as septic shock and other inflammatory disorders. the trif-related adaptor molecule (tram) adaptor protein is unique to the tlr4 signaling pathway and abrogation of tram-mediated tlr4 ... | 2016 | 26264972 |
| identification of restriction factors by human genome-wide rna interference screening of viral host range mutants exemplified by discovery of samd9 and wdr6 as inhibitors of the vaccinia virus k1l-c7l- mutant. | rna interference (rnai) screens intended to identify host factors that restrict virus replication may fail if the virus already counteracts host defense mechanisms. to overcome this limitation, we are investigating the use of viral host range mutants that exhibit impaired replication in nonpermissive cells. a vaccinia virus (vacv) mutant with a deletion of both the c7l and k1l genes, k1l(-)c7l(-), which abrogates replication in human cells at a step prior to late gene expression, was chosen for ... | 2015 | 26242627 |
| vaccinia virus strain lc16m8 defective in the b5r gene keeps strong protection comparable to its parental strain lister in immunodeficient mice. | attenuated vaccinia virus strain, lc16m8, defective in the b5r envelope protein gene, is used as a stockpile smallpox vaccine strain in japan against bioterrorism: the defect in the b5r gene mainly contributes to its highly attenuated properties. | 2015 | 26241947 |
| horizontal study of vaccinia virus infections in an endemic area: epidemiologic, phylogenetic and economic aspects. | vaccinia virus (vacv), the etiological agent of bovine vaccinia (bv), is widespread in brazil and present in most of the milk-producing regions. we conducted a horizontal study of bv in bahia, a state of brazil in which the production of milk is increasing. during 2011, human and bovine clinical samples were collected during outbreaks for bv diagnosis, virus isolation and molecular analysis. we collected data for epidemiological inferences. vaccinia virus was detected in 87.7% of the analyzed ou ... | 2015 | 26239343 |
| bioluminescent imaging of vaccinia virus infection in immunocompetent and immunodeficient rats as a model for human smallpox. | due to the increasing concern of using smallpox virus as biological weapons for terrorist attack, there is renewed interest in studying the pathogenesis of human smallpox and development of new therapies. animal models are highly demanded for efficacy and safety examination of new vaccines and therapeutic drugs. here, we demonstrated that both wild type and immunodeficient rats infected with an engineered vaccinia virus carrying firefly luciferase reporter gene (rtv-fluc) could recapitulate infe ... | 2015 | 26235050 |
| vaccinia virus b1 kinase is required for postreplicative stages of the viral life cycle in a baf-independent manner in u2os cells. | the vaccinia virus b1r gene encodes a highly conserved protein kinase that is essential for the poxviral life cycle. as demonstrated in many cell types, b1 plays a critical role during viral dna replication when it inactivates the cellular host defense effector barrier to autointegration factor (baf or banf1). to better understand the role of b1 during infection, we have characterized the growth of a b1-deficient temperature-sensitive mutant virus (cts2 virus) in u2os osteosarcoma cells. in cont ... | 2015 | 26223647 |
| vegf-mediated induction of prd1-bf1/blimp1 expression sensitizes tumor vasculature to oncolytic virus infection. | oncolytic viruses designed to attack malignant cells can in addition infect and destroy tumor vascular endothelial cells. we show here that this expanded tropism of oncolytic vaccinia virus to the endothelial compartment is a consequence of vegf-mediated suppression of the intrinsic antiviral response. vegf/vegfr2 signaling through erk1/2 and stat3 leads to upregulation, nuclear localization, and activation of the transcription repressor prd1-bf1/blimp1. prd1-bf1 does not contribute to the mitog ... | 2015 | 26212250 |
| preclinical testing oncolytic vaccinia virus strain glv-5b451 expressing an anti-vegf single-chain antibody for canine cancer therapy. | virotherapy on the basis of oncolytic vaccinia virus (vacv) strains is a novel approach for canine cancer therapy. here we describe, for the first time, the characterization and the use of vacv strain glv-5b451 expressing the anti-vascular endothelial growth factor (vegf) single-chain antibody (scab) glaf-2 as therapeutic agent against different canine cancers. cell culture data demonstrated that glv-5b451 efficiently infected and destroyed all four tested canine cancer cell lines including: mam ... | 2015 | 26205404 |
| doxycycline inducible melanogenic vaccinia virus as theranostic anti-cancer agent. | we reported earlier the diagnostic potential of a melanogenic vaccinia virus based system in magnetic resonance (mri) and optoacoustic deep tissue imaging (msot). since melanin overproduction lead to attenuated virus replication, we constructed a novel recombinant vaccinia virus strain (rvacv), glv-1h462, which expressed the key enzyme of melanogenesis (tyrosinase) under the control of an inducible promoter-system. in this study melanin production was detected after exogenous addition of doxycyc ... | 2015 | 26199644 |
| extent of systemic spread determines cd8+ t cell immunodominance for laboratory strains, smallpox vaccines, and zoonotic isolates of vaccinia virus. | cd8(+) t cells that recognize virus-derived peptides presented on mhc class i are vital antiviral effectors. such peptides presented by any given virus vary greatly in immunogenicity, allowing them to be ranked in an immunodominance hierarchy. however, the full range of parameters that determine immunodominance and the underlying mechanisms remain unknown. in this study, we show across a range of vaccinia virus strains, including the current clonal smallpox vaccine, that the ability of a strain ... | 2015 | 26195812 |
| quantitative analysis of micrornas in vaccinia virus infection reveals diversity in their susceptibility to modification and suppression. | vaccinia virus (vacv) is a large cytoplasmic dna virus that causes dramatic alterations to many cellular pathways including microrna biogenesis. the virus encodes a poly(a) polymerase which was previously shown to add poly(a) tails to the 3' end of cellular mirnas, resulting in their degradation by 24 hours post infection (hpi). here we used small rna sequencing to quantify the impact of vacv infection on cellular mirnas in human cells at both early (6 h) and late (24 h) times post infection. a ... | 2015 | 26161560 |
| are bites the "missing link" in cancer therapy? | conventional treatment for cancer routinely includes surgical resection and some combination of chemotherapy and radiation. these approaches are frequently accompanied by unintended and highly toxic collateral damage to healthy tissues, which are offset by only marginal prognostic improvements in patients with advanced cancers. this unfortunate balance has driven the development of novel therapies that aim to target tumors both safely and efficiently. over the past decade, mounting evidence has ... | 2015 | 26155413 |
| microglia and astrocytes attenuate the replication of the oncolytic vaccinia virus livp 1.1.1 in murine gl261 gliomas by acting as vaccinia virus traps. | oncolytic virotherapy is a novel approach for the treatment of glioblastoma multiforme (gbm) which is still a fatal disease. pathologic features of gbm are characterized by the infiltration with microglia/macrophages and a strong interaction between immune- and glioma cells. the aim of this study was to determine the role of microglia and astrocytes for oncolytic vaccinia virus (vacv) therapy of gbm. | 2015 | 26149494 |
| sensitive electrochemical detection of vaccinia virus in a solution containing a high concentration of l-ascorbic acid. | washing processes cannot fully remove interfering species that remain on biosensing surfaces when a sample solution contains a high concentration of interfering species. this study reports an immunosensing scheme employing electroreduction-based electrochemical-chemical (ec) redox cycling that allows sensitive detection of vaccinia virus (vv) in a solution containing a high concentration of l-ascorbic acid (aa). to obtain high signal amplification, an enzymatic reaction by β-d-galactosidase (gal ... | 2015 | 26149118 |
| a role for the small gtpase rac1 in vaccinia actin-based motility. | vaccinia virus dissemination relies on the recruitment of the nucleation promoting factor n-wasp underneath cell-associated extracellular virus (cevs) and subsequent recruitment and activation of the arp2/3 complex, a major actin nucleator of the host cell. we have recently discovered that, in addition to the n-wasp/arp2/3 pathway, vaccinia actin-based motility also relies on the small gtpase rac1 and its downstream effector the formin-type actin nucleator fhod1. here we discuss the potential si ... | 2015 | 26147090 |
| phase 1b trial of biweekly intravenous pexa-vec (jx-594), an oncolytic and immunotherapeutic vaccinia virus in colorectal cancer. | fifteen patients with treatment-refractory colorectal cancer were enrolled on a phase 1b study of pexa-vec (pexastimogene devacirepvec; jx-594), an oncolytic and immunotherapeutic vaccinia designed to selectively replicate in cancer cells. pexa-vec was administered intravenously every 14 days, at dose levels of 1 × 10(6), 1 × 10(7), or 3 × 10(7) plaque-forming units (pfu)/kg. the primary endpoint was to determine the maximum tolerated dose. secondary endpoints were pharmacokinetics and pharmacod ... | 2015 | 26073886 |
| a phase 2, open-label, randomized study of pexa-vec (jx-594) administered by intratumoral injection in patients with unresectable primary hepatocellular carcinoma. | primary liver cancer (hepatocellular carcinoma; hcc) in patients not eligible for surgery or transplant is currently treated by locoregional therapeutic approaches, including trans-arterial chemoembolization and radiofrequency ablation. sorafenib (nexavar; bayer/onyx) is currently the only approved systemic therapy for patients having failed locoregional interventions. oncolytic viruses are designed to selectively replicate within, and subsequently lyse, cancer cells by a unique mechanisms-of-ac ... | 2015 | 26072416 |
| use of glv-1h68 for vaccinia virotherapy and monitoring. | herein we describe the use of the vaccinia virus strain glv-1h68 as a theragnostic agent in cancer models. to date, glv-1h68 has been used successfully in more than 50 xenograft tumor models. the recombinant vaccinia virus strain has been equipped with heterologous expression cassettes for a luciferase-fluorescent protein fusion gene, bacterial beta-galactosidase, as well as a bacterial glucuronidase. the methods to investigate and monitor glv-1h68 mediated virotherapy, including optical imaging ... | 2015 | 26072410 |
| binding of undamaged double stranded dna to vaccinia virus uracil-dna glycosylase. | uracil-dna glycosylases are evolutionarily conserved dna repair enzymes. however, vaccinia virus uracil-dna glycosylase (known as d4), also serves as an intrinsic and essential component of the processive dna polymerase complex during dna replication. in this complex d4 binds to a unique poxvirus specific protein a20 which tethers it to the dna polymerase. at the replication fork the dna scanning and repair function of d4 is coupled with dna replication. so far, dna-binding to d4 has not been st ... | 2015 | 26031450 |
| oncolytic vaccinia virus synergizes with irinotecan in colorectal cancer. | metastatic colorectal cancer (crc) is complex clinical challenge for which there are limited treatment options. chemotherapy with or without surgery provides moderate improvements in overall survival and quality of life; nevertheless the 5-year survival remains below 30%. oncolytic vaccinia virus (vv) shows strong anti-tumour activity in models of crc, however transient delays in disease progression are insufficient to lead to long-term survival. here we examined the efficacy of vv with oxalipla ... | 2015 | 26004084 |
| socs1 mimetics and antagonists: a complementary approach to positive and negative regulation of immune function. | suppressors of cytokine signaling (socs) are inducible intracellular proteins that play essential regulatory roles in both immune and non-immune function. of the eight known members, socs1 and socs3 in conjunction with regulatory t cells play key roles in regulation of the immune system. molecular tools such as gene transfections and sirna have played a major role in our functional understanding of the socs proteins where a key functional domain of 12-amino acid residues called the kinase inhibi ... | 2015 | 25954276 |
| smallpox vaccine, acam2000: sites and duration of viral shedding and effect of povidone iodine on scarification site shedding and immune response. | the u.s. department of defense vaccinates personnel deployed to high-risk areas with the vaccinia virus (vacv)-based smallpox vaccine. autoinoculations and secondary and tertiary transmissions due to vacv shedding from the vaccination site continue to occur despite education of vaccinees on the risks of such infections. the objectives of this study were to investigate, in naïve smallpox vaccinees, (a) whether the vaccination site can remain contagious after the scab separates and (b) whether the ... | 2015 | 25930115 |
| laboratory-acquired vaccinia virus infection in a recently immunized person--massachusetts, 2013. | on november 26, 2013, the cdc poxvirus laboratory was notified by the boston public health commission (bphc) of an inadvertent inoculation of a recently vaccinated (acam2000 smallpox vaccine) laboratory worker with wild type vaccinia virus (vacv) western reserve. a joint investigation by cdc and bphc confirmed orthopoxvirus infection in the worker, who had reported a needle stick in his thumb while inoculating a mouse with vacv. he experienced a non-tender, red rash on his arm, diagnosed at a lo ... | 2015 | 25928468 |
| deciphering poxvirus gene expression by rna sequencing and ribosome profiling. | the more than 200 closely spaced annotated open reading frames, extensive transcriptional read-through, and numerous unpredicted rna start sites have made the analysis of vaccinia virus gene expression challenging. genome-wide ribosome profiling provided an unprecedented assessment of poxvirus gene expression. by 4 h after infection, approximately 80% of the ribosome-associated mrna was viral. ribosome-associated mrnas were detected for most annotated early genes at 2 h and for most intermediate ... | 2015 | 25903347 |
| the mechanisms of genetically modified vaccinia viruses for the treatment of cancer. | the use of oncolytic viruses for the treatment of cancer is an emerging field of cancer research and therapy. oncolytic viruses are designed to induce tumor specific immunity while replicating selectively within cancer cells to cause lysis of the tumor cells. while there are several forms of oncolytic viruses, the use of vaccinia viruses for oncolysis may be more beneficial than other forms of oncolytic viruses. for example, vaccinia viruses have been shown to exert their anti-tumor effects thro ... | 2015 | 25900073 |
| lister strain vaccinia virus with thymidine kinase gene deletion is a tractable platform for development of a new generation of oncolytic virus. | vaccinia virus (vv) has many attractive characteristics as a potential cancer therapeutic. there are several strains of vv. the nonvaccine strain western reserve vv with deletion of both the thymidine kinase and the viral growth factor genes (known as wrdd) has been reported as the most potent tumor-targeted oncolytic vv. other strains, such as the european vaccine lister strain, are largely untested. this study evaluated the antitumor potency and biodistribution of different vv strains using in ... | 2015 | 25876464 |
| immunomodulator-based enhancement of anti smallpox immune responses. | the current live vaccinia virus vaccine used in the prevention of smallpox is contraindicated for millions of immune-compromised individuals. although vaccination with the current smallpox vaccine produces protective immunity, it might result in mild to serious health complications for some vaccinees. thus, there is a critical need for the production of a safe virus-free vaccine against smallpox that is available to everyone. for that reason, we investigated the impact of imiquimod and resiquimo ... | 2015 | 25875833 |
| the vaccinia virus e6 protein influences virion protein localization during virus assembly. | vaccinia virus mutants in which expression of the virion core protein gene e6r is repressed are defective in virion morphogenesis. e6 deficient infections fail to properly package viroplasm into viral membranes, resulting in an accumulation of empty immature virions and large aggregates of viroplasm. we have used immunogold electron microscopy and immunofluorescence confocal microscopy to assess the intracellular localization of several virion structural proteins and enzymes during e6r mutant in ... | 2015 | 25863879 |
| genetic confirmation that the h5 protein is required for vaccinia virus dna replication. | the duplication of the poxvirus double-stranded dna genome occurs in cytoplasmic membrane-delimited factories. this physical autonomy from the host nucleus suggests that poxvirus genomes encode the full repertoire of proteins committed for genome replication. biochemical and genetic analyses have confirmed that six viral proteins are required for efficient dna synthesis; indirect evidence has suggested that the multifunctional h5 protein may also have a role. here we show that h5 localizes to re ... | 2015 | 25855734 |
| erv enhances spatial learning and prevents the development of infarcts, accompanied by upregulated bdnf in the cortex. | an anti-allergic and analgesic drug, "an extract derived from the inflamed cutaneous tissue of rabbits inoculated with vaccinia virus (erv)", has been used in medical practice in japan and some other countries. we examined the effect of erv, prior to induction of ischemia, on the development of cerebral infarction, on learning and memory, or on brain-derived neurotrophic factor (bdnf) levels in c57bl/6j mice. | 2015 | 25842373 |
| outbreak of severe zoonotic vaccinia virus infection, southeastern brazil. | in 2010, a vaccinia virus isolate caused an atypically severe outbreak that affected humans and cattle in brazil. of 26 rural workers affected, 12 were hospitalized. our data raise questions about the risk factors related to the increasing number and severity of vaccinia virus infections. | 2015 | 25811411 |
| complement inhibition prevents oncolytic vaccinia virus neutralization in immune humans and cynomolgus macaques. | oncolytic viruses (ovs) have shown promising clinical activity when administered by direct intratumoral injection. however, natural barriers in the blood, including antibodies and complement, are likely to limit the ability to repeatedly administer ovs by the intravenous route. we demonstrate here that for a prototype of the clinical vaccinia virus based product pexa-vec, the neutralizing activity of antibodies elicited by smallpox vaccination, as well as the anamnestic response in hyperimmune v ... | 2015 | 25807289 |
| incomplete but infectious vaccinia virions are produced in the absence of oncolysis in feline sccf1 cells. | vaccinia virus is a large, enveloped virus of the poxvirus family. it has broad tropism and typically virus replication culminates in accumulation and lytic release of intracellular mature virus (imv), the most abundant form of infectious virus, as well as release by budding of extracellular enveloped virus (eev). vaccinia viruses have been modified to replicate selectively in cancer cells and clinically tested as oncolytic agents. during preclinical screening of relevant cancer targets for a re ... | 2015 | 25799430 |
| infected cells call their killers to the scene of the crime. | effector cd8(+) t cells scan tissues to locate and kill infected host cells. in this issue of immunity, hickman et al. (2015) show that the exploration is not random: infected monocytes attract their assassins by secreting chemokines, which accelerates clearance of epicutaneous vaccinia virus infection. | 2015 | 25786170 |
| cxcr3 chemokine receptor enables local cd8(+) t cell migration for the destruction of virus-infected cells. | cd8(+) t cells play a critical role in limiting peripheral virus replication, yet how they locate virus-infected cells within tissues is unknown. here, we have examined the environmental signals that cd8(+) t cells use to localize and eliminate virus-infected skin cells. epicutaneous vaccinia virus (vv) infection, mimicking human smallpox vaccination, greatly increased expression of the cxcr3 chemokine receptor ligands cxcl9 and cxcl10 in vv-infected skin. despite normal t cell numbers in the sk ... | 2015 | 25769612 |
| variola virus f1l is a bcl-2-like protein that unlike its vaccinia virus counterpart inhibits apoptosis independent of bim. | subversion of host cell apoptosis is an important survival strategy for viruses to ensure their own proliferation and survival. certain viruses express proteins homologous in sequence, structure and function to mammalian pro-survival b-cell lymphoma 2 (bcl-2) proteins, which prevent rapid clearance of infected host cells. in vaccinia virus (vv), the virulence factor f1l was shown to be a potent inhibitor of apoptosis that functions primarily be engaging pro-apoptotic bim. variola virus (var), th ... | 2015 | 25766319 |
| cellular 5'-3' mrna exonuclease xrn1 controls double-stranded rna accumulation and anti-viral responses. | by accelerating global mrna decay, many viruses impair host protein synthesis, limiting host defenses and stimulating virus mrna translation. vaccinia virus (vacv) encodes two decapping enzymes (d9, d10) that remove protective 5' caps on mrnas, presumably generating substrates for degradation by the host exonuclease xrn1. surprisingly, we find vacv infection of xrn1-depleted cells inhibits protein synthesis, compromising virus growth. these effects are aggravated by d9 deficiency and dependent u ... | 2015 | 25766294 |
| poxvirus decapping enzymes enhance virulence by preventing the accumulation of dsrna and the induction of innate antiviral responses. | poxvirus replication involves synthesis of double-stranded rna (dsrna), which can trigger antiviral responses by inducing phosphorylation-mediated activation of protein kinase r (pkr) and stimulating 2'5'-oligoadenylate synthetase (oas). pkr inactivates the translation initiation factor eif2α via phosphorylation, while oas induces the endonuclease rnase l to degrade rna. we show that poxvirus decapping enzymes d9 and d10, which remove caps from mrnas, inhibit these antiviral responses by prevent ... | 2015 | 25766293 |
| vaccinia virus protein a3 is required for the production of normal immature virions and for the encapsidation of the nucleocapsid protein l4. | maturation of the vaccinia virion is an intricate process that results in the organization of the viroplasm contained in immature virions into the lateral bodies, core wall and nucleocapsid observed in the mature particles. it is unclear how this organization takes place and studies with mutants are indispensable in understanding this process. by characterizing an inducible mutant in the a3l gene, we revealed that a3, an inner core wall protein, is important for formation of normal immature viru ... | 2015 | 25765002 |
| topology of endoplasmic reticulum-associated cellular and viral proteins determined with split-gfp. | the split green fluorescent protein (gfp) system was adapted for investigation of the topology of er-associated proteins. a 215-amino acid fragment of gfp (s1-10) was expressed in the cytoplasm as a free protein or fused to the n-terminus of calnexin and in the er as an intraluminal protein or fused to the c-terminus of calnexin. a 16-amino acid fragment of gfp (s11) was fused to the n- or c-terminus of the target protein. fluorescence occurred when both gfp fragments were in the same intracellu ... | 2015 | 25761760 |
| vaccinia virus protein complex f12/e2 interacts with kinesin light chain isoform 2 to engage the kinesin-1 motor complex. | during vaccinia virus morphogenesis, intracellular mature virus (imv) particles are wrapped by a double lipid bilayer to form triple enveloped virions called intracellular enveloped virus (iev). iev are then transported to the cell surface where the outer iev membrane fuses with the cell membrane to expose a double enveloped virion outside the cell. the f12, e2 and a36 proteins are involved in transport of ievs to the cell surface. deletion of the f12l or e2l genes causes a severe inhibition of ... | 2015 | 25760349 |
| simultaneous quantification of viral antigen expression kinetics using data-independent (dia) mass spectrometry. | the generation of antigen-specific reagents is a significant bottleneck in the study of complex pathogens that express many hundreds to thousands of different proteins or to emerging or new strains of viruses that display potential pandemic qualities and therefore require rapid investigation. in these instances the development of antibodies for example can be prohibitively expensive to cover the full pathogen proteome, or the lead time may be unacceptably long in urgent cases where new highly pa ... | 2015 | 25755296 |
| efficiently editing the vaccinia virus genome by using the crispr-cas9 system. | vaccinia virus (vacv) continues to be used in immunotherapy for the prevention of infectious diseases and treatment of cancer since its use for the eradication of smallpox. however, the current method of editing the vacv genome is not efficient. here, we demonstrate that the crispr-cas9 system can be used to edit the vacv genome rapidly and efficiently. additionally, a set of 8,964 computationally designed unique guide rnas (grnas) targeting all vacv genes will be valuable for the study of vacv ... | 2015 | 25741005 |
| poxvirus membrane biogenesis. | poxviruses differ from most dna viruses by replicating entirely within the cytoplasm. the first discernible viral structures are crescents and spherical immature virions containing a single lipoprotein membrane bilayer with an external honeycomb lattice. because this viral membrane displays no obvious continuity with a cellular organelle, a de novo origin was suggested. nevertheless, transient connections between viral and cellular membranes could be difficult to resolve. despite the absence of ... | 2015 | 25728299 |
| progress in clinical oncolytic virus-based therapy for hepatocellular carcinoma. | hepatocellular carcinoma (hcc) carries a dismal prognosis, with advanced disease being resistant to both radiotherapy and conventional cytotoxic drugs, whilst anti-angiogenic drugs are marginally efficacious. oncolytic viruses (ovs) offer the promise of selective cancer therapy through direct and immune-mediated mechanisms. the premise of ovs lies in their preferential genomic replication, protein expression and productive infection of malignant cells. numerous ovs are being tested in preclinica ... | 2015 | 25711964 |
| host proteome correlates of vaccine-mediated enhanced disease in a mouse model of respiratory syncytial virus infection. | respiratory syncytial virus (rsv) is the leading cause of lower respiratory tract infections in infants. despite over 50 years of research, to date no safe and efficacious rsv vaccine has been licensed. many experimental vaccination strategies failed to induce balanced t-helper (th) responses and were associated with adverse effects such as hypersensitivity and immunopathology upon challenge. in this study, we explored the well-established recombinant vaccinia virus (rvv) rsv-f/rsv-g vaccination ... | 2015 | 25694607 |
| the role of signalling and the cytoskeleton during vaccinia virus egress. | viruses are obligate intracellular parasites that are critically dependent on their hosts to replicate and generate new progeny. to achieve this goal, viruses have evolved numerous elegant strategies to subvert and utilise the different cellular machineries and processes of their unwilling hosts. moreover, they often accomplish this feat with a surprisingly limited number of proteins. among the different systems of the cell, the cytoskeleton is often one of the first to be hijacked as it provide ... | 2015 | 25681743 |
| evaluation of virus inactivation by formaldehyde to enhance biosafety of diagnostic electron microscopy. | formaldehyde (fa) fixation of infectious samples is a well-established protocol in diagnostic electron microscopy of viruses. however, published experimental data that demonstrate virus inactivation by these fixation procedures are lacking. usually, fixation is performed immediately before the sample preparation for microscopy. the fixation procedure should transform viruses in a non-infectious but nonetheless structurally intact form in order to allow a proper diagnosis based on morphology. fa ... | 2015 | 25674771 |
| enhancing tumor-specific intracellular delivering efficiency of cell-penetrating peptide by fusion with a peptide targeting to egfr. | cell-penetrating peptides (cpps) are well known as intracellular delivery vectors. however, unsatisfactory delivery efficiency and poor specificity are challenging barriers to cpp applications at the clinical trial stage. here, we showed that s3, an egfr-binding domain derived from vaccinia virus growth factor, when fused to a cpp such as hbd or tat can substantially enhance its internalization efficiency and tumor selectivity. the uptake of s3-hbd (s3h) recombinant molecule by tumor cells was n ... | 2015 | 25655386 |
| filaggrin deficiency promotes the dissemination of cutaneously inoculated vaccinia virus. | eczema vaccinatum is a life-threatening complication of smallpox vaccination in patients with atopic dermatitis (ad) characterized by dissemination of vaccinia virus (vv) in the skin and internal organs. mutations in the filaggrin (flg) gene, the most common genetic risk factor for ad, confer a greater risk for eczema herpeticum in patients with ad, suggesting that it impairs the response to cutaneous viral infections. | 2015 | 25649082 |
| mouse model for pre-clinical study of human cancer immunotherapy. | this unit describes protocols for developing tumors in mice, including subcutaneous growth, pulmonary metastases of b16 melanoma, and spontaneous melanoma in b-raf v600e/pten deletion transgenic mouse models. two immunization methods to prevent b16 tumor growth are described using b16.gm-csf and recombinant vaccinia virus. a therapeutic approach is also included that uses adoptive transfer of tumor antigen-specific t cells. methods including ctl induction, isolation, testing, and genetic modific ... | 2015 | 25640991 |
| intracellular transport of vaccinia virus in hela cells requires wash-vpef/fam21-retromer complexes and recycling molecules rab11 and rab22. | vaccinia virus, the prototype of the orthopoxvirus genus in the family poxviridae, infects a wide range of cell lines and animals. vaccinia mature virus particles of the wr strain reportedly enter hela cells through fluid-phase endocytosis. however, the intracellular trafficking process of the vaccinia mature virus between cellular uptake and membrane fusion remains unknown. we used live imaging of single virus particles with a combination of various cellular vesicle markers, to track fluorescen ... | 2015 | 26041286 |
| a versatile salicyl hydrazonic ligand and its metal complexes as antiviral agents. | acylhydrazones are very versatile ligands and their coordination properties can be easily tuned, giving rise to metal complexes with different nuclearities. in the last few years, we have been looking for new pharmacophores able to coordinate simultaneously two metal ions, because many enzymes have two metal ions in the active site and their coordination can be a successful strategy to inhibit the activity of the metalloenzyme. as a part of this ongoing research, we synthesized the acylhydrazone ... | 2015 | 26047528 |
| oncolytic gene therapy with recombinant vaccinia strain glv-2b372 efficiently kills hepatocellular carcinoma. | hepatocellular carcinoma (hcc) commonly presents at a late stage when surgery is no longer a curative option. as such, novel therapies for advanced hcc are needed. oncolytic viruses are a viable option for cancer therapy owing to their ability to specifically infect, replicate within, and kill cancer cells. in this study, we have investigated the ability of glv-2b372, a novel light-emitting recombinant vaccinia virus derived from a wild-type lister strain, to kill hcc. | 2015 | 26049609 |
| the addition of recombinant vaccinia her2/neu to oncolytic vaccinia-gmcsf given into the tumor microenvironment overcomes mdsc-mediated immune escape and systemic anergy. | effective immunotherapeutic strategies require the ability to generate a systemic antigen-specific response capable of impacting both primary and metastatic disease. we have built on our oncolytic vaccinia a granulocyte-macrophage colony-stimulating factor (gm-csf) strategy by adding recombinant tumor antigen to increase the response in the tumor microenvironment and systemically. in the present study, orthotopic growth of a syngeneic her2/neu-overexpressing mammary carcinoma in fvb/n mice (nbt1 ... | 2015 | 25633483 |
| could hantavirus circulation superpose areas of highly endemic vaccinia virus outbreaks? a retrospective seroepidemiological study in state of minas gerais. | hantavirus infections have been described in several regions in brazil through seroepidemiological studies. usually, populations are associated with rural and wild environment mainly due to close contact to species of sigmodontinae rodents, considered hantavirus reservoirs. | 2015 | 25626659 |
| pushing with actin: from cells to pathogens. | actin polymerization is harnessed by cells to generate lamellipodia for movement and by a subclass of pathogens to facilitate invasion of their infected hosts. using electron tomography (et), we have shown that lamellipodia are formed via the generation of subsets of actin filaments joined by branch junctions. image averaging produced a 2.9 nm resolution model of branch junctions in situ and revealed a close fit to the electron density map of the actin-related protein 2/3 (arp2/3)-actin complex ... | 2015 | 25619250 |
| gene therapy using therapeutic and diagnostic recombinant oncolytic vaccinia virus glv-1h153 for management of colorectal peritoneal carcinomatosis. | peritoneal carcinomatosis (pc) is a terminal progression of colorectal cancer (crc). poor response to cytoreductive operation and chemotherapy coupled with the inability to reliably track disease progression by the use of established diagnostic methods, make this a deadly disease. we examined the effectiveness of the oncolytic vaccinia virus glv-1h153 as a therapeutic and diagnostic vehicle. we believe that viral expression of the human sodium iodide transporter (hnis) provides both real-time mo ... | 2015 | 25616946 |
| dermal-resident versus recruited γδ t cell response to cutaneous vaccinia virus infection. | the study of t cell immunity at barrier surfaces has largely focused on t cells bearing the αβ tcr. however, t cells that express the γδ tcr are disproportionately represented in peripheral tissues of mice and humans, suggesting they too may play an important role responding to external stimuli. in this article, we report that, in a murine model of cutaneous infection with vaccinia virus, dermal γδ t cell numbers increased 10-fold in the infected ear and resulted in a novel γδ t cell population ... | 2015 | 25609844 |
| vaccinia virus protein a49 is an unexpected member of the b-cell lymphoma (bcl)-2 protein family. | vaccinia virus (vacv) encodes several proteins that inhibit activation of the proinflammatory transcription factor nuclear factor κb (nf-κb). vacv protein a49 prevents translocation of nf-κb to the nucleus by sequestering cellular β-trcp, a protein required for the degradation of the inhibitor of κb. a49 does not share overall sequence similarity with any protein of known structure or function. we solved the crystal structure of a49 from vacv western reserve to 1.8 å resolution and showed, surpr ... | 2015 | 25605733 |
| 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 |
| intratumoral inf-γ triggers an antiviral state in gl261 tumor cells: a major hurdle to overcome for oncolytic vaccinia virus therapy of cancer. | oncolytic vaccinia virus (vacv) therapy is an alternative treatment option for glioblastoma multiforme. here, we used a comparison of different tumor locations and different immunologic and genetic backgrounds to determine the replication efficacy and oncolytic potential of the vacv livp 1.1.1, an attenuated wild-type isolate of the lister strain, in murine gl261 glioma models. with this approach, we expected to identify microenvironmental factors, which may be decisive for failure or success of ... | 2015 | 27119106 |
| expression of anti-vegf antibody together with anti-egfr or anti-fap enhances tumor regression as a result of vaccinia virotherapy. | the tumor microenvironment plays an important role in tumor growth and progression. here we demonstrate that vaccinia virus-mediated, constitutively expressed intratumoral antibodies against vascular endothelial growth factor (vegf), epidermal growth factor receptor (egfr), and fibroblast activation protein (fap) significantly improved tumor regression and oncolytic virotherapy through suppression of angiogenesis, cell proliferation, and stromagenesis in virus-colonized tumors. in contrast to th ... | 2015 | 27119102 |
| overcoming tumor resistance by heterologous adeno-poxvirus combination therapy. | successful cancer control relies on overcoming resistance to cell death and on activation of host antitumor immunity. oncolytic viruses are particularly attractive in this regard, as they lyse infected tumor cells and trigger robust immune responses during the infection. however, repeated injections of the same virus promote antiviral rather than antitumor immunity and tumors may mount innate antiviral defenses to restrict oncolytic virus replication. in this article, we have explored if alterna ... | 2015 | 27119097 |
| cd4(+) t-cell dependence of primary cd8(+) t-cell response against vaccinia virus depends upon route of infection and viral dose. | cd4(+) t-cell help (cd4 help) plays a pivotal role in cd8(+) t-cell responses against viral infections. however, the role in primary cd8(+) t-cell responses remains controversial. we evaluated the effects of infection route and viral dose on primary cd8(+) t-cell responses to vaccinia virus (vacv) in mhc class ii(-/-) mice. cd4 help deficiency diminished the generation of vacv-specific cd8(+) t cells after intraperitoneal (i.p.) but not after intranasal (i.n.) infection. a large viral dose could ... | 2016 | 25544501 |
| phase 1 study of intratumoral pexa-vec (jx-594), an oncolytic and immunotherapeutic vaccinia virus, in pediatric cancer patients. | pexa-vec (pexastimogene devacirepvec, jx-594) is an oncolytic and immunotherapeutic vaccinia virus designed to destroy cancer cells through viral lysis and induction of granulocyte-macrophage colony-stimulating factor (gm-csf)-driven tumor-specific immunity. pexa-vec has undergone phase 1 and 2 testing alone and in combination with other therapies in adult patients, via both intratumoral and intravenous administration routes. we sought to determine the safety of intratumoral administration in pe ... | 2015 | 25531693 |
| mcl1 enhances the survival of cd8+ memory t cells after viral infection. | viral infection results in the generation of massive numbers of activated effector cd8(+) t cells that recognize viral components. most of these are short-lived effector t cells (slecs) that die after clearance of the virus. however, a small proportion of this population survives and forms antigen-specific memory precursor effector cells (mpecs), which ultimately develop into memory cells. these can participate in a recall response upon reexposure to antigen even at protracted times postinfectio ... | 2015 | 25505074 |
| a polymeric conjugate foreignizing tumor cells for targeted immunotherapy in vivo. | antigen-specific cd8(+) cytotoxic t lymphocytes (ctls) are key elements of immunological rejection in transplantation as well as cancer immunotherapy. most tumors, however, are not immunologically rejected because they have self antigens, which are not recognized as the foreigner by ctls. in this study, we hypothesized that "foreignizing" tumor cells by delivering non-self foreign antigens into the tumors would result in rejection by foreign antigen-reactive ctls. as the model system to foreigni ... | 2015 | 25499555 |
| programmed necrosis in the cross talk of cell death and inflammation. | cell proliferation and cell death are integral elements in maintaining homeostatic balance in metazoans. disease pathologies ensue when these processes are disturbed. a plethora of evidence indicates that malfunction of cell death can lead to inflammation, autoimmunity, or immunodeficiency. programmed necrosis or necroptosis is a form of nonapoptotic cell death driven by the receptor interacting protein kinase 3 (ripk3) and its substrate, mixed lineage kinase domain-like (mlkl). ripk3 partners w ... | 2015 | 25493335 |
| fine structure of the vaccinia virion determined by controlled degradation and immunolocalization. | the vaccinia virion is a membraned, slightly flattened, barrel-shaped particle, with a complex internal structure featuring a biconcave core flanked by lateral bodies. although the architecture of the purified mature virion has been intensely characterized by electron microscopy, the distribution of the proteins within the virion has been examined primarily using biochemical procedures. thus, it has been shown that non-ionic and ionic detergents combined or not with a sulfhydryl reagent can be u ... | 2015 | 25486587 |
| tailored immunity by skin antigen-presenting cells. | skin vaccination aims at targeting epidermal and dermal antigen-presenting cells (apcs), indeed many subsets of different origin endowed with various functions populate the skin. the idea that the skin could represent a particularly potent site to induce adaptive and protective immune response emerged after the success of vaccinia virus vaccination by skin scarification. recent advances have shown that multiple subsets of apcs coexist in the skin and participate in immunity to infectious disease ... | 2015 | 25483512 |
| a role for the small gtpase rac1 in vaccinia actin-based motility. | vaccinia virus dissemination relies on the recruitment of the nucleation promoting factor n-wasp underneath cell-associated extracellular virus (cevs) and subsequent recruitment and activation of the arp2/3 complex, a major actin nucleator of the host cell. we have recently discovered that, in addition to the n-wasp/arp2/3 pathway, vaccinia actin-based motility also relies on the small gtpase rac1 and its downstream effector the formin-type actin nucleator fhod1. here we discuss the potential si ... | 2014 | 25483216 |
| antigen profiling analysis of vaccinia virus injected canine tumors: oncolytic virus efficiency predicted by boolean models. | virotherapy on the basis of oncolytic vaccinia virus (vacv) strains is a novel approach for cancer therapy. in this study we describe for the first time the use of dynamic boolean modeling for tumor growth prediction of vaccinia virus glv-1h68-injected canine tumors including canine mammary adenoma (zmth3), canine mammary carcinoma (mth52c), canine prostate carcinoma (ct1258), and canine soft tissue sarcoma (stsa-1). additionally, the stsa-1 xenografted mice were injected with either livp 1.1.1 ... | 2017 | 25482233 |
| murine anti-vaccinia virus d8 antibodies target different epitopes and differ in their ability to block d8 binding to cs-e. | the imv envelope protein d8 is an adhesion molecule and a major immunodominant antigen of vaccinia virus (vacv). here we identified the optimal d8 ligand to be chondroitin sulfate e (cs-e). cs-e is characterized by a disaccharide moiety with two sulfated hydroxyl groups at positions 4' and 6' of galnac. to study the role of antibodies in preventing d8 adhesion to cs-e, we have used a panel of murine monoclonal antibodies, and tested their ability to compete with cs-e for d8 binding. among four a ... | 2014 | 25474621 |
| structure-function analysis of vaccinia virus h7 protein reveals a novel phosphoinositide binding fold essential for poxvirus replication. | phosphoinositides and phosphoinositide binding proteins play a critical role in membrane and protein trafficking in eukaryotes. their critical role in replication of cytoplasmic viruses has just begun to be understood. poxviruses, a family of large cytoplasmic dna viruses, rely on the intracellular membranes to develop their envelope, and poxvirus morphogenesis requires enzymes from the cellular phosphoinositide metabolic pathway. however, the role of phosphoinositides in poxvirus replication re ... | 2015 | 25473060 |
| rab1a promotes vaccinia virus replication by facilitating the production of intracellular enveloped virions. | vaccinia virus (vacv) is a large double-stranded dna virus with a complex cytoplasmic replication cycle that exploits numerous cellular proteins. this work characterises the role of a proviral cellular protein, the small gtpase rab1a, in vacv replication. using sirna, we identified rab1a as required for the production of extracellular enveloped virions (eevs), but not intracellular mature virions (imvs). immunofluorescence and electron microscopy further refined the role of rab1a as facilitating ... | 2015 | 25462347 |
| neurotropin promotes ngf signaling through interaction of gm1 ganglioside with trk neurotrophin receptor in pc12 cells. | activation of the high-affinity nerve growth factor (ngf) receptor trk occurs through multiple processes consisted of translocation and clustering within the plasma membrane lipid rafts, dimerization and autophosphorylation. here we found that a nonprotein extract of inflamed rabbit skin inoculated with vaccinia virus (neurotropin(®)) enhanced efficiency of ngf signaling. in rat pheochromocytoma pc12 cells overexpressing trk (pctrk cells), neurotropin augmented insufficient neurite outgrowth obs ... | 2015 | 25454796 |
| non-coding rnas and heme oxygenase-1 in vaccinia virus infection. | small nuclear rnas (snrnas) are <200 nucleotide non-coding uridylate-rich rnas. although the functions of many snrnas remain undetermined, a population of snrnas is produced during the early phase of infection of cells by vaccinia virus. in the present study, we demonstrate a direct correlation between expression of the cytoprotective enzyme heme oxygenase-1 (ho-1), suppression of selective snrna expression, and inhibition of vaccinia virus infection of macrophages. hemin induced ho-1 expression ... | 2014 | 25450361 |
| cytokine production associated with smallpox vaccine responses. | smallpox was eradicated 34 years ago due to the success of the smallpox vaccine; yet, the vaccine continues to be studied because of its importance in responding to potential biological warfare and the adverse events associated with current smallpox vaccines. interindividual variations in vaccine response are observed and are, in part, due to genetic variation. in some cases, these varying responses lead to adverse events, which occur at a relatively high rate for the smallpox vaccine compared w ... | 2014 | 25428648 |
| vaccinia virus induces rapid necrosis in keratinocytes by a stat3-dependent mechanism. | humans with a dominant negative mutation in stat3 are susceptible to severe skin infections, suggesting an essential role for stat3 signaling in defense against cutaneous pathogens. | 2014 | 25419841 |
| a vaccinia virus armed with interleukin-10 is a promising therapeutic agent for treatment of murine pancreatic cancer. | vaccinia virus has strong potential as a novel therapeutic agent for treatment of pancreatic cancer. we investigated whether arming vaccinia virus with interleukin-10 (il10) could enhance the antitumor efficacy with the view that il10 might dampen the host immunity to the virus, increasing viral persistence, thus maximizing the oncolytic effect and antitumor immunity associated with vaccinia virus. | 2015 | 25416195 |
| evolution of and evolutionary relationships between extant vaccinia virus strains. | although vaccinia virus (vacv) was once used as a vaccine to eradicate smallpox on a worldwide scale, the biological origins of vacv are uncertain, as are the historical relationships between the different strains once used as smallpox vaccines. here, we sequenced additional vacv strains that either represent relatively pristine examples of old vaccines (e.g., dryvax, lister, and tashkent) or have been subjected to additional laboratory passage (e.g., ihd-w and wr). these genome sequences were c ... | 2015 | 25410873 |
| a novel vaccinia virus with dual oncolytic and anti-angiogenic therapeutic effects against triple-negative breast cancer. | vascular endothelial growth factor (vegf) expression is higher in triple-negative breast cancers (tnbc) compared to other subtypes and is reported to predict incidence of distant metastases and shorter overall survival. we investigated the therapeutic impact of a vaccinia virus (vacv) glv-1h164 (derived from its parent virus glv-1h100), encoding a single-chain antibody (scab) against vegf (glaf-2) in an orthotopic tnbc murine model. glv-1h164 was tested against multiple tnbc cell lines. viral in ... | 2014 | 25391896 |
| a mouse model of atopic dermatitis. | atopic dermatitis (ad) is a chronic or chronically relapsing, pruritic inflammatory skin disease. the incidence of ad has dramatically increased for the past three decades in industrialized countries. we established a highly efficient method to induce ad-like skin lesions using repeated epicutaneous treatments with house dust mite allergen and staphylococcal enterotoxin b (seb). the dermatitis-induced mice showed increased serum ige levels that were similar to human ad patients and also treatabl ... | 2015 | 25388270 |
| enhanced efficacy of cidofovir combined with vaccinia immune globulin in treating progressive cutaneous vaccinia virus infections in immunosuppressed hairless mice. | the treatment of progressive vaccinia in individuals has involved antiviral drugs, such as cidofovir (cdv), brincidofovir, and/or tecovirimat, combined with vaccinia immune globulin (vig). vig is costly, and its supply is limited, so sparing the use of vig during treatment is an important objective. vig sparing was modeled in immunosuppressed mice by maximizing the treatment benefits of cdv combined with vig to determine the effective treatments that delayed the time to death, reduced cutaneous ... | 2015 | 25385098 |
| enhancement of cd8(+) t-cell memory by removal of a vaccinia virus nuclear factor-κb inhibitor. | factors influencing t-cell responses are important for vaccine development but are incompletely understood. here, vaccinia virus (vacv) protein n1 is shown to impair the development of both effector and memory cd8(+) t cells and this correlates with its inhibition of nuclear factor-κb (nf-κb) activation. infection with vacvs that either have the n1l gene deleted (vδn1) or contain a i6e mutation (vn1.i6e) that abrogates its inhibition of nf-κb resulted in increased central and memory cd8(+) t-cel ... | 2015 | 25382035 |
| apoptin enhances the oncolytic properties of vaccinia virus and modifies mechanisms of tumor regression. | a recombinant vaccinia virus vvdgf-apos24/2 expressing apoptin selectively kills human cancer cells in vitro [kochneva et al., 2013]. we compared the oncolytic activity of this recombinant with that of the parental strain l-ivp using a model of human a431 carcinoma xenografts in nude mice. single intratumoral injections (2×10^7 pfu/mouse) of the viruses produced a dramatic decrease in tumor volumes, which was higher after injection of apoptin-producing virus. the tumor dried out after the inject ... | 2014 | 25358248 |
| a role for vaccinia virus protein c16 in reprogramming cellular energy metabolism. | vaccinia virus (vacv) is a large dna virus that replicates in the cytoplasm and encodes about 200 proteins of which approximately 50 % may be non-essential for viral replication. these proteins enable vacv to suppress transcription and translation of cellular genes, to inhibit the innate immune response, to exploit microtubule- and actin-based transport for virus entry and spread, and to subvert cellular metabolism for the benefit of the virus. vacv strain wr protein c16 induces stabilization of ... | 2015 | 25351724 |
| cxcl12/cxcr4 blockade by oncolytic virotherapy inhibits ovarian cancer growth by decreasing immunosuppression and targeting cancer-initiating cells. | signals mediated by the chemokine cxcl12 and its receptor cxcr4 are involved in the progression of ovarian cancer through enhancement of tumor angiogenesis and immunosuppressive networks that regulate dissemination of peritoneal metastasis and development of cancer-initiating cells (cics). in this study, we investigated the antitumor efficacy of a cxcr4 antagonist expressed by oncolytic vaccinia virus (ovv) against an invasive variant of the murine epithelial ovarian cancer cell line id8-t. this ... | 2014 | 25320277 |
| anti-tumour activity of oncolytic western reserve vaccinia viruses in canine tumour cell lines, xenografts, and fresh tumour biopsies. | cancer is one of the most common reasons for death in dogs. one promising approach is oncolytic virotherapy. we assessed the oncolytic effect of genetically modified vaccinia viruses in canine cancer cells, in freshly excised tumour biopsies, and in mice harbouring canine tumour xenografts. tumour transduction efficacy was assessed using virus expressing luciferase or fluorescent marker genes and oncolysis was quantified by a colorimetric cell viability assay. oncolytic efficacy in vivo was eval ... | 2014 | 25302859 |