Publications
| Title | Abstract | Year Filter | PMID(sorted ascending) Filter |
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| [immunogenicity and heterologous protection in mice with a recombinant adenoviral-based vaccine carrying a hepatitis c virus truncated ns3 and core fusion protein]. | to develop a safe and broad-spectrum effective hepatitis c virus (hcv) t cell vaccine,we constructed the recombinant adenovirus-based vaccine that carried the hepatitis c virus truncated ns3 and core fusion proteins. the expression of the fusion antigen was confirmed by in vitro immunofluorescence and western blotting assays. our results indicated that this vaccine not only stimulated antigen-specific antibody responses,but also activated strong ns3-specific t cell immune responses. ns3-specific ... | 2015 | 25997323 |
| vaccinia virus transmission through experimentally contaminated milk using a murine model. | bovine vaccinia (bv) is a zoonosis caused by vaccinia virus (vacv), which affects dairy cattle and humans. previous studies have detected the presence of viable virus particles in bovine milk samples naturally and experimentally contaminated with vacv. however, it is not known whether milk contaminated with vacv could be a route of viral transmission. however, anti-orthopoxvirus antibodies were detected in humans from bv endemic areas, whom had no contact with affected cows, which suggest that o ... | 2015 | 26000966 |
| 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 |
| characterization and implementation of a diverse simian immunodeficiency virus sivsm envelope panel in the assessment of neutralizing antibody breadth elicited in rhesus macaques by multimodal vaccines expressing the sivmac239 envelope. | antibodies that can neutralize diverse viral strains are likely to be an important component of a protective human immunodeficiency virus type 1 (hiv-1) vaccine. to this end, preclinical simian immunodeficiency virus (siv)-based nonhuman primate immunization regimens have been designed to evaluate and enhance antibody-mediated protection. however, these trials often rely on a limited selection of siv strains with extreme neutralization phenotypes to assess vaccine-elicited antibody activity. to ... | 2015 | 26018167 |
| humoral responses to hivconsv induced by heterologous vaccine modalities in rhesus macaques. | vaccines delivering t cell immunogen hivconsv vectored by plasmid dna, non-replicating simian adenovirus and non-replicating modified vaccinia virus ankara (mva) are under clinical evaluation in phase i/iia trials in uk, europe, and africa. while these vaccines aim to induce effector t cell responses specific for hiv-1, we here characterized the humoral responses induced by hivconsv administration to macaques using six different vaccine modalities: plasmid dna, human adenovirus serotype 5, simia ... | 2015 | 26029368 |
| 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 |
| 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 |
| crystal structure of the vaccinia virus uracil-dna glycosylase in complex with dna. | vaccinia virus polymerase holoenzyme is composed of the dna polymerase catalytic subunit e9 associated with its heterodimeric co-factor a20·d4 required for processive genome synthesis. although a20 has no known enzymatic activity, d4 is an active uracil-dna glycosylase (ung). the presence of a repair enzyme as a component of the viral replication machinery suggests that, for poxviruses, dna synthesis and base excision repair is coupled. we present the 2.7 å crystal structure of the complex forme ... | 2015 | 26045555 |
| 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 |
| viral apoptotic mimicry. | as opportunistic pathogens, viruses have evolved many elegant strategies to manipulate host cells for infectious entry and replication. viral apoptotic mimicry, defined by the exposure of phosphatidylserine - a marker for apoptosis - on the pathogen surface, is emerging as a common theme used by enveloped viruses to promote infection. focusing on the four best described examples (vaccinia virus, dengue virus, ebola virus and pseudotyped lentivirus), we summarize our current understanding of apop ... | 2015 | 26052667 |
| 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 |
| 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 |
| 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 |
| comparison of monovalent glycoprotein b with bivalent gb/pp65 (gp83) vaccine for congenital cytomegalovirus infection in a guinea pig model: inclusion of gp83 reduces gb antibody response but both vaccine approaches provide equivalent protection against pup mortality. | cytomegalovirus (cmv) subunit vaccine candidates include glycoprotein b (gb), and phosphoprotein ppul83 (pp65). using a guinea pig cytomegalovirus (gpcmv) model, this study compared immunogenicity, pregnancy outcome, and congenital viral infection following pre-pregnancy immunization with a three-dose series of modified vaccinia virus ankara (mva)-vectored vaccines consisting either of gb administered alone, or simultaneously with a pp65 homolog (gp83)-expressing vaccine. vaccinated and control ... | 2015 | 26079615 |
| orf virus inhibits interferon stimulated gene expression and modulates the jak/stat signalling pathway. | interferons (ifns) play a critical role as a first line of defence against viral infection. activation of the janus kinase/signal transducer and activation of transcription (jak/stat) pathway by ifns leads to the production of ifn stimulated genes (isgs) that block viral replication. the parapoxvirus, orf virus (orfv) induces acute pustular skin lesions of sheep and goats and is transmissible to man. the virus replicates in keratinocytes that are the immune sentinels of skin. we investigated whe ... | 2015 | 26113305 |
| codelivery of envelope protein in alum with mva vaccine induces cxcr3-biased cxcr5+ and cxcr5- cd4 t cell responses in rhesus macaques. | the goal of an hiv vaccine is to generate robust and durable protective ab. vital to this goal is the induction of cd4(+) t follicular helper (tfh) cells. however, very little is known about the tfh response to hiv vaccination and its relative contribution to magnitude and quality of vaccine-elicited ab titers. in this study, we investigated these questions in the context of a dna/modified vaccinia virus ankara siv vaccine with and without gp140 boost in aluminum hydroxide in rhesus macaques. in ... | 2015 | 26116502 |
| brca1 regulates ifi16 mediated nuclear innate sensing of herpes viral dna and subsequent induction of the innate inflammasome and interferon-β responses. | the innate immune system pattern recognition receptors (prr) are the first line of host defenses recognizing the various pathogen- or danger-associated molecular patterns and eliciting defenses by regulating the production of pro-inflammatory cytokines such as il-1β, il-18 or interferon β (ifn-β). nod-like receptors (nlrs) and aim2-like receptors (alrs) are cytoplasmic inflammasome sensors of foreign molecules, including dna. ifi16, a sequence-independent nuclear innate sensor alr, recognizes ep ... | 2015 | 26121674 |
| herpesvirus genome recognition induced acetylation of nuclear ifi16 is essential for its cytoplasmic translocation, inflammasome and ifn-β responses. | the il-1β and type i interferon-β (ifn-β) molecules are important inflammatory cytokines elicited by the eukaryotic host as innate immune responses against invading pathogens and danger signals. recently, a predominantly nuclear gamma-interferon-inducible protein 16 (ifi16) involved in transcriptional regulation has emerged as an innate dna sensor which induced il-1β and ifn-β production through inflammasome and sting activation, respectively. herpesvirus (kshv, ebv, and hsv-1) episomal dsdna ge ... | 2015 | 26134128 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| complementation of the human adenovirus type 5 va rnai defect by the vaccinia virus e3l protein and serotype-specific va rnais. | human adenoviruses (hadvs) encode for multifunctional non-coding virus-associated (va) rnas, which function as powerful suppressors of the cellular interferon (ifn) and rna interference (rnai) systems. in this study we tested the ability of various plant and animal virus encoded rnai and ifn suppressor proteins to functionally substitute for the hadv-5 va rnai. our results revealed that only the vaccinia virus (vacv) e3l protein was able to substitute for the hadv-5 va rnai functions in virus-in ... | 2015 | 26196231 |
| mucosal immunization with newcastle disease virus vector coexpressing hiv-1 env and gag proteins elicits potent serum, mucosal, and cellular immune responses that protect against vaccinia virus env and gag challenges. | newcastle disease virus (ndv) avirulent strain lasota was used to coexpress gp160 env and p55 gag from a single vector to enhance both env-specific and gag-specific immune responses. the optimal transcription position for both env and gag genes in the ndv genome was determined by generating recombinant ndv (rndv)-env-gag (gp160 located between the p and m genes and gag between the hn and l genes), rndv-gag-env (gag located between the p and m genes and gp160 between the hn and l genes), rndv-env ... | 2015 | 26199332 |
| 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 |
| experimental evolution identifies vaccinia virus mutations in a24r and a35r that antagonize the protein kinase r pathway and accompany collapse of an extragenic gene amplification. | most new human infectious diseases emerge from cross-species pathogen transmissions; however, it is not clear how viruses adapt to productively infect new hosts. host restriction factors represent one species-specific barrier that viruses may initially have little ability to inhibit in new hosts. for example, viral antagonists of protein kinase r (pkr) vary in their ability to block pkr-mediated inhibition of viral replication, in part due to pkr allelic variation between species. we previously ... | 2015 | 26202237 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| development of oral ctl vaccine using a ctp-integrated sabin 1 poliovirus-based vector system. | we developed a ctl vaccine vector by modification of the rps-vax system, a mucosal vaccine vector derived from a poliovirus sabin 1 strain, and generated an oral ctl vaccine against hiv-1. a dna fragment encoding a cytoplasmic transduction peptide (ctp) was integrated into the rps-vax system to generate rps-ctp, a ctl vaccine vector. an hiv-1 p24 cdna fragment was introduced into the rps-ctp vector system and a recombinant poliovirus (rec-pv) named vrps-ctp/p24 was produced. vrps-ctp/p24 was gen ... | 2015 | 26241946 |
| 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 |
| 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 |
| evasion of the innate immune type i interferon system by monkeypox virus. | the vaccinia virus (vacv) e3 protein has been shown to be important for blocking activation of the cellular innate immune system and allowing viral replication to occur unhindered. mutation or deletion of e3l severely affects viral host range and pathogenesis. while the monkeypox virus (mpxv) genome encodes a homologue of the vacv e3 protein, encoded by the f3l gene, the mpxv gene is predicted to encode a protein with a truncation of 37 n-terminal amino acids. vacv with a genome encoding a simil ... | 2015 | 26246580 |
| expression of chicken interleukin-2 by a highly virulent strain of newcastle disease virus leads to decreased systemic viral load but does not significantly affect mortality in chickens. | in mammals, interleukin 2 (il-2) has been shown to decrease replication or attenuate pathogenicity of numerous viral pathogens (herpes simplex virus, vaccinia virus, human respiratory syncytial virus, human immunodeficiency virus) by activating natural killer cells (nk), cytotoxic t lymphocytes and expanding subsets of memory cells. in chickens, il-2 has been shown to activate t cells, and as such it might have the potential to affect replication and pathogenesis of newcastle disease virus (ndv) ... | 2015 | 26253150 |
| breakthrough of siv strain sme660 challenge in siv strain mac239-vaccinated rhesus macaques despite potent autologous neutralizing antibody responses. | although the correlates of immunological protection from human immunodeficiency virus or simian immunodeficiency virus infection remain incompletely understood, it is generally believed that medium to high titers of serum neutralizing antibodies (nabs) against the challenge virus will prevent infection. this paradigm is based on a series of studies in which passive transfer of hiv-specific nabs protected rhesus macaques (rms) from subsequent mucosal challenge with a chimeric human/simian immunod ... | 2015 | 26261312 |
| 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 |
| cytotoxic t cell vaccination with plga microspheres interferes with influenza a virus replication in the lung and suppresses the infectious disease. | current influenza virus vaccines aim to elicit antibodies directed toward viral surface glycoproteins, which however are prone to antigenic drift. cytotoxic t lymphocytes (ctls) can exhibit heterosubtypic immunity against most influenza a viruses. in our study, we encapsulated the highly conserved, immunodominant, hla-a*0201 restricted epitope from the influenza virus matrix protein m158-66 together with tlr ligands in biodegradable poly(d,l-lactide-co-glycolide) (plga) microspheres. subcutaneou ... | 2015 | 26276509 |
| 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 |
| 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 |
| 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 |
| semliki forest virus and sindbis virus, but not vaccinia virus, require glycolysis for optimal replication. | viruses are obligate intracellular pathogens which rely on the cell's machinery to produce the energy and macromolecules required for replication. infection is associated with a modified metabolic profile and one pathway which can be modified is glycolysis. in this study, we investigated if the glycolysis pathway is required for alphavirus replication. pre-treatment of vero cells with three different glycolysis inhibitors (2-deoxyglucose, lonidamine and oxamate) resulted in a significant reducti ... | 2015 | 26297236 |
| isolation and characterization of monoclonal antibodies against a virion core protein of orf virus strain na1/11 as potential diagnostic tool for orf viruses. | orf is caused by the orf virus (orfv) and is a non-systemic, widespread disease afflicting sheep, goats, wild ruminants, and humans. recent outbreaks in sheep and goats in jilin and other northern chinese provinces raise concerns about orf control in china. thirty-five hybridoma clones were constructed from splenocytes of balb/c mice immunized with natural orf virus protein. these hybridomas were used to produce antibodies targeting orfv proteins. immunological characterization of these monoclon ... | 2015 | 26301926 |
| mutations in the di-dii linker of human parainfluenza virus type 3 fusion protein result in diminished fusion activity. | human parainfluenza virus type 3 (hpiv3) can cause severe respiratory tract diseases in infants and young children, but no licensed vaccines or antiviral agents are currently available for treatment. fusing the viral and target cell membranes is a prerequisite for its entry into host cells and is directly mediated by the fusion (f) protein. although several domains of f are known to have important effects on regulating the membrane fusion activity, the roles of the di-dii linker (residues 369-37 ... | 2015 | 26305905 |
| 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 |
| sex difference in immune response to vaccination: a participant-level meta-analysis of randomized trials of imvamune smallpox vaccine. | previous research shows immune response to vaccination differs by sex but this has not been explored for imvamune, a replication-deficient smallpox vaccine developed in response to the potential for bioterrorism using smallpox. | 2015 | 26319063 |
| structural analysis and immunogenicity of recombinant major envelope protein (ra27l) of buffalopox virus, a zoonotic indian vaccinia-like virus. | buffalopox virus (bpxv), an indian variant of vaccinia virus (vacv), is a zoonotic agent and affects buffaloes, cattle and humans. a27l is one of the conserved major immuno-dominant envelope proteins of orthopox viruses (opvs) involved in viral entry/maturation and elicits neutralizing antibodies. in this study, the a27l gene of bpxv-vij/96 strain encoding recombinant mature a27l (21s to e110) and c-terminal truncated a27l-lzd (21s to n84aa) proteins were cloned and over-expressed in escherichia ... | 2015 | 26319070 |
| structural and functional characterization of anti-a33 antibodies reveal a potent cross-species orthopoxviruses neutralizer. | vaccinia virus a33 is an extracellular enveloped virus (eev)-specific type ii membrane glycoprotein that is essential for efficient eev formation and long-range viral spread within the host. a33 is a target for neutralizing antibody responses against eev. in this study, we produced seven murine anti-a33 monoclonal antibodies (mabs) by immunizing mice with live vacv, followed by boosting with the soluble a33 homodimeric ectodomain. five a33 specific mabs were capable of neutralizing eev in the pr ... | 2015 | 26325270 |
| 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 |
| vaccinia virus lc16m8∆ as a vaccine vector for clinical applications. | the lc16m8 strain of vaccinia virus, the active ingredient in the japanese smallpox vaccine, was derived from the lister/elstree strain. lc16m8 is replication-competent and has been administered to over 100,000 infants and 3,000 adults with no serious adverse reactions. despite this outstanding safety profile, the occurrence of spontaneously-generated large plaque-forming virulent lc16m8 revertants following passage in cell culture is a major drawback. we identified the gene responsible for the ... | 2014 | 26344890 |
| drug-encoded biomarkers for monitoring biological therapies. | blood tests are necessary, easy-to-perform and low-cost alternatives for monitoring of oncolytic virotherapy and other biological therapies in translational research. here we assessed three candidate proteins with the potential to be used as biomarkers in biological fluids: two glucuronidases from e. coli (gusa) and staphylococcus sp. rlh1 (gusplus), and the luciferase from gaussia princeps (gluc). the three genes encoding these proteins were inserted individually into vaccinia virus glv-1h68 ge ... | 2015 | 26348361 |
| vaccine-derived neutralizing antibodies to the human cytomegalovirus gh/gl pentamer potently block primary cytotrophoblast infection. | human cytomegalovirus (hcmv) elicits neutralizing antibodies (nab) of various potencies and cell type specificities to prevent hcmv entry into fibroblasts (fb) and epithelial/endothelial cells (epc/enc). nab targeting the major essential envelope glycoprotein complexes gb and gh/gl inhibit both fb and epc/enc entry. in contrast to fb infection, hcmv entry into epc/enc is additionally blocked by extremely potent nab to conformational epitopes of the gh/gl/ul128/130/131a pentamer complex (pc). we ... | 2015 | 26378171 |
| genomic analysis, phenotype, and virulence of the historical brazilian smallpox vaccine strain ioc: implications for the origins and evolutionary relationships of vaccinia virus. | smallpox was declared eradicated in 1980 after an intensive vaccination program using different strains of vaccinia virus (vacv; poxviridae). vacv strain ioc (vacv-ioc) was the seed strain of the smallpox vaccine manufactured by the major vaccine producer in brazil during the smallpox eradication program. however, little is known about the biological and immunological features as well as the phylogenetic relationships of this first-generation vaccine. in this work, we present a comprehensive cha ... | 2015 | 26378174 |
| a multiplex pcr/ldr assay for the simultaneous identification of category a infectious pathogens: agents of viral hemorrhagic fever and variola virus. | cdc designated category a infectious agents pose a major risk to national security and require special action for public health preparedness. they include viruses that cause viral hemorrhagic fever (vhf) syndrome as well as variola virus, the agent of smallpox. vhf is characterized by hemorrhage and fever with multi-organ failure leading to high morbidity and mortality. smallpox, a prior scourge, has been eradicated for decades, making it a particularly serious threat if released nefariously in ... | 2015 | 26381398 |
| 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 |
| 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 |
| 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 |
| delivery of antigen to nasal-associated lymphoid tissue microfold cells through secretory iga targeting local dendritic cells confers protective immunity. | transmission of mucosal pathogens relies on their ability to bind to the surfaces of epithelial cells, to cross this thin barrier, and to gain access to target cells and tissues, leading to systemic infection. this implies that pathogen-specific immunity at mucosal sites is critical for the control of infectious agents using these routes to enter the body. although mucosal delivery would ensure the best onset of protective immunity, most of the candidate vaccines are administered through the par ... | 2016 | 26414879 |
| a marker-free system for highly efficient construction of vaccinia virus vectors using crispr cas9. | the current method for creation of vaccinia virus (vacv) vectors involves using a selection and purification marker, however inclusion of a gene without therapeutic value in the resulting vector is not desirable for clinical use. the cre-loxp system has been used to make marker-free poxviruses, but the efficiency was very low. to obtain a marker-free vacv vector, we developed marker gene excision systems to modify the thymidine kinase (tk) region and n1l regions using cre-loxp and flp-fret syste ... | 2015 | 26417609 |
| development of a high-content orthopoxvirus infectivity and neutralization assays. | currently, a number of assays measure orthopoxvirus neutralization with serum from individuals, vaccinated against smallpox. in addition to the traditional plaque reduction neutralization test (prnt), newer higher throughput assays are based on neutralization of recombinant vaccinia virus, expressing reporter genes such as β-galactosidase or green fluorescent protein. these methods could not be used to evaluate neutralization of variola virus, since genetic manipulations of this virus are prohib ... | 2015 | 26426117 |
| decoding poxvirus genome. | 2015 | 26429864 | |
| a multicenter, open-label, controlled phase ii study to evaluate safety and immunogenicity of mva smallpox vaccine (imvamune) in 18-40 year old subjects with diagnosed atopic dermatitis. | replicating smallpox vaccines can cause severe complications in individuals with atopic dermatitis (ad). prior studies evaluating modified vaccinia ankara virus (mva), a non-replicating vaccine in humans, showed a favorable safety and immunogenicity profile in healthy volunteers. | 2015 | 26439129 |
| akt kinase-mediated checkpoint of cgas dna sensing pathway. | upon dna stimulation, cyclic gmp-amp synthase (cgas) synthesizes the second messenger cyclic gmp-amp (cgamp) that binds to the sting, triggering antiviral interferon-β (ifn-β) production. however, it has remained undetermined how hosts regulate cgas enzymatic activity after the resolution of dna immunogen. here, we show that akt kinase plays a negative role in cgas-mediated anti-viral immune response. akt phosphorylated the s291 or s305 residue of the enzymatic domain of mouse or human cgas, res ... | 2015 | 26440888 |
| enhanced production of a single domain antibody with an engineered stabilizing extra disulfide bond. | single domain antibodies derived from the variable region of the unique heavy chain antibodies found in camelids yield high affinity and regenerable recognition elements. adding an additional disulfide bond that bridges framework regions is a proven method to increase their melting temperature, however often at the expense of protein production. to fulfill their full potential it is essential to achieve robust protein production of these stable binding elements. in this work, we tested the hypot ... | 2015 | 26449768 |
| mouse superkiller-2-like helicase ddx60 is dispensable for type i ifn induction and immunity to multiple viruses. | ifn-α/β allow cells to fight virus infection by inducing the expression of many genes that encode effectors of antiviral defense. one of these, the ski2-like dexh-box helicase ddx60, was recently implicated in resistance of human cells to hepatitis c virus, as well as in induction of ifn-α/β by retinoic acid inducible gene 1-like receptors (rlrs) that detect the presence of rna viruses in a cell-intrinsic manner. here, we sought to investigate the role of ddx60 in ifn-α/β induction and in resist ... | 2015 | 26457795 |
| viruses that ride on the coat-tails of actin nucleation. | actin nucleation drives a diversity of critical cellular processes and the motility of a select group of viral pathogens. vaccinia virus and baculovirus, autographa californica multiple nucleopolyhedrovirus, recruit and activate the cellular actin nucleator, the arp2/3 complex, at the surface of virus particles thereby instigating highly localized actin nucleation. the extension of these filaments provides a mechanical force that bestows the ability to navigate the intracellular environment and ... | 2015 | 26459972 |
| engineered nanoconstructs for the multiplexed and sensitive detection of high-risk pathogens. | many countries categorize the causative agents of severe infectious diseases as high-risk pathogens. given their extreme infectivity and potential to be used as biological weapons, a rapid and sensitive method for detection of high-risk pathogens (e.g., bacillus anthracis, francisella tularensis, yersinia pestis, and vaccinia virus) is highly desirable. here, we report the construction of a novel detection platform comprising two units: (1) magnetic beads separately conjugated with multiple capt ... | 2016 | 26462853 |
| natural killer cells and innate interferon gamma participate in the host defense against respiratory vaccinia virus infection. | in establishing a respiratory infection, vaccinia virus (vacv) initially replicates in airway epithelial cells before spreading to secondary sites of infection, mainly the draining lymph nodes, spleen, gastrointestinal tract, and reproductive organs. we recently reported that interferon gamma (ifn-γ) produced by cd8 t cells ultimately controls this disseminated infection, but the relative contribution of ifn-γ early in infection is unknown. investigating the role of innate immune cells, we found ... | 2015 | 26468539 |
| isolation of vaccinia jx594 from pustules following therapy for hepatocellular carcinoma. | jx594 is an oncolytic poxvirus derived from wyeth strain vaccinia virus. we reported the presentation of cutaneous and mucosal pustules containing laboratory-confirmed jx594 in a patient following injection of jx594. | 2015 | 26471278 |
| the generation of cd8+ t-cell population specific for vaccinia virus epitope involved in the antiviral protection against ectromelia virus challenge. | eradication of smallpox has led to cessation of vaccination programs. this has rendered the human population increasingly susceptible not only to variola virus infection but also to infections with other representatives of poxviridae family that cause zoonotic variola-like diseases. thus, new approaches for designing improved vaccine against smallpox are required. discovering that orthopoxviruses, e.g. variola virus, vaccinia virus, ectromelia virus, share common immunodominant antigen, may resu ... | 2015 | 26474845 |
| biochemical analysis of the multifunctional vaccinia mrna capping enzyme encoded by a temperature sensitive virus mutant. | prior biochemical analysis of the heterodimeric vaccinia virus mrna capping enzyme suggests roles not only in mrna capping but also in early viral gene transcription termination and intermediate viral gene transcription initiation. prior phenotypic characterization of dts36, a temperature sensitive virus mutant affecting the large subunit of the capping enzyme was consistent with the multifunctional roles of the capping enzyme in vivo. we report a biochemical analysis of the capping enzyme encod ... | 2016 | 26496697 |
| interferon induction by avian reovirus. | we have previously shown that the replication of avian reovirus (arv) in chicken embryo fibroblasts (cef) is more resistant to the antiviral action of interferon (ifn) than the replication of vesicular stomatitis virus (vsv) or vaccinia virus (vv). in this study we examined the capacity of these three viruses to induce the expression of ifn when infecting avian cells. efficient expression of both type-α and type-β ifns, as well as of the double-stranded rna (dsrna)-activated protein kinase (pkr) ... | 2016 | 26517397 |
| evaluating anti-orthopoxvirus antibodies in individuals from brazilian rural areas prior to the bovine vaccinia era. | vaccinia virus naturally circulates in brazil and is the causative agent of a zoonotic disease known as bovine vaccinia (bv). we retrospectively evaluated two populations from the amazon and southeast regions. bv outbreaks had not been reported in these regions before sample collection. neutralising antibodies were found in 13 individuals (n = 132) with titres ranging from 100 ≥ 6,400 neutralising units/ml. univariate analysis identified age and vaccination as statistically significant risk fact ... | 2015 | 26517662 |
| subtle cxcr3-dependent chemotaxis of ctls within infected tissue allows efficient target localization. | it is well established how effector t cells exit the vasculature to enter the peripheral tissues in which an infection is ongoing. however, less is known regarding how ctls migrate toward infected cells after entry into peripheral organs. recently, it was shown that the chemokine receptor cxcr3 on t cells has an important role in their ability to localize infected cells and to control vaccinia virus infection. however, the search strategy of t cells for virus-infected targets has not been invest ... | 2015 | 26525288 |
| ebolavirus vaccines: progress in the fight against ebola virus disease. | ebolaviruses are highly infectious pathogens that cause lethal ebola virus disease (evd) in humans and non-human primates (nhps). due to their high pathogenicity and transmissibility, as well as the potential to be misused as a bioterrorism agent, ebolaviruses would threaten the health of global populations if not controlled. in this review, we describe the origin and structure of ebolaviruses and the development of vaccines from the beginning of the 1980s, including conventional ebolavirus vacc ... | 2015 | 26535889 |
| detection of vaccinia virus in milk: evidence of a systemic and persistent infection in experimentally infected cows. | bovine vaccinia (bv) is a zoonosis caused by vaccinia virus (vacv), which affects lactating cows and milkers. vacv dna and infectious particles have been detected in milk of naturally infected cows. however, the period and pattern of vacv shedding in milk is unknown, as is whether the presence of vacv in milk is due to a localized or a systemic infection. to address those questions, eight lactating cows were inoculated with vacv in previously scarified teats. the experiment was divided in two ph ... | 2015 | 26545169 |
| mir-150 regulates differentiation and cytolytic effector function in cd8+ t cells. | micrornas regulate most mammalian genes, and they control numerous aspects of immune system development and function. their precise roles in the cd8+ t cell response, however, remain unclear. in this report, we show that in the absence of the microrna mir-150, cd8+ t cells fail to undergo robust expansion and differentiation into short-lived terminal effector cells in response to primary infection with listeria monocytogenes or vaccinia virus. notably, even after transitioning into the memory po ... | 2015 | 26549197 |
| comparison of the cowpox virus and vaccinia virus mature virion proteome: analysis of the species- and strain-specific proteome. | cowpox virus (cpxv) causes most zoonotic orthopoxvirus (opv) infections in europe and northern as well as central asia. the virus has the broadest host range of opv and is transmitted to humans from rodents and other wild or domestic animals. increasing numbers of human cpxv infections in a population with declining immunity have raised concerns about the virus' zoonotic potential. while there have been reports on the proteome of other human-pathogenic opv, namely vaccinia virus (vacv) and monke ... | 2015 | 26556597 |
| cd40 ligand-expressing recombinant vaccinia virus promotes the generation of cd8(+) central memory t cells. | central memory cd8(+) t cells (tcm ) play key roles in the protective immunity against infectious agents, cancer immunotherapy, and adoptive treatments of malignant and viral diseases. cd8(+) tcm cells are characterized by specific phenotypes, homing, and proliferative capacities. however, cd8(+) tcm -cell generation is challenging, and usually requires cd4(+) cd40l(+) t-cell "help" during the priming of naïve cd8(+) t cells. we have generated a replication incompetent cd40 ligand-expressing rec ... | 2016 | 26561341 |
| structural basis for antagonizing a host restriction factor by c7 family of poxvirus host-range proteins. | human sterile alpha motif domain-containing 9 (samd9) protein is a host restriction factor for poxviruses, but it can be overcome by some poxvirus host-range proteins that share homology with vaccinia virus c7 protein. to understand the mechanism of action for this important family of host-range factors, we determined the crystal structures of c7 and myxoma virus m64, a c7 family member that is unable to antagonize samd9. despite their different functions and only 23% sequence identity, the two ... | 2015 | 26578811 |
| alternative routes of zoonotic vaccinia virus transmission, brazil. | 2015 | 26583465 | |
| recombinant vaccinia virus glv-1h68 is a promising oncolytic vector in the treatment of cholangiocarcinoma. | although early stage cholangiocarcinoma (cc) can be cured by surgical extirpation, the options for treatment of advanced stage cc are very few and suboptimal. oncolytic virotherapy using replication-competent vaccinia virus (vacv) is a promising new strategy to treat human cancers. the ability of oncolytic vacv glv-1h68 to infect, replicate in, and lyse three human cc cell lines was assayed in vitro and in subcutaneous flank xenografts in athymic nude mice. in this study, we have demonstrated th ... | 2015 | 26584530 |
| vaccinia virus, a promising new therapeutic agent for pancreatic cancer. | the poor prognosis of pancreatic cancer patients signifies a need for radically new therapeutic strategies. tumor-targeted oncolytic viruses have emerged as attractive therapeutic candidates for cancer treatment due to their inherent ability to specifically target and lyse tumor cells as well as induce antitumor effects by multiple action mechanisms. vaccinia virus has several inherent features that make it particularly suitable for use as an oncolytic agent. in this review, we will discuss the ... | 2015 | 26595180 |
| cholesterol flux is required for endosomal progression of african swine fever virions during the initial establishment of infection. | african swine fever virus (asfv) is a major threat for porcine production that has been slowly spreading in eastern europe since its first appearance in the caucasus in 2007. asfv enters the cell by endocytosis and gains access to the cytosol to start replication from late endosomes and multivesicular bodies. cholesterol associated with low-density lipoproteins entering the cell by endocytosis also follows a trafficking pathway similar to that of asfv. here we show that cholesterol plays an esse ... | 2015 | 26608317 |
| integration of linear and dendritic actin nucleation in nck-induced actin comets. | the nck adaptor protein recruits cytosolic effectors such as n-wasp that induce localized actin polymerization. experimental aggregation of nck sh3 domains at the membrane induces actin comet tails--dynamic, elongated filamentous actin structures similar to those that drive the movement of microbial pathogens such as vaccinia virus. here we show that experimental manipulation of the balance between unbranched/branched nucleation altered the morphology and dynamics of nck-induced actin comets. in ... | 2016 | 26609071 |
| microbiota is an essential element for mice to initiate a protective immunity against vaccinia virus. | the gastrointestinal tract of vertebrates harbors one of the most complex ecosystems known in microbial ecology and this indigenous microbiota almost always has a profound influence on host-parasite relationships, which can enhance or reduce the pathology of the infection. in this context, the impact of the microbiota during the infection of several viral groups remains poorly studied, including the family poxviridae. vaccinia virus (vacv) is a member of this family and is the causative agent of ... | 2016 | 26610433 |
| [a new simple technique for producing labeled monoclonal antibodies for antibody pair screening in sandwich-elisa]. | a simple and fast method for obtaining biotin-labeled monoclonal antibodies was developed usingcontent of hybridoma culture supernatant sufficient to select antibody pairs in sandwich elisa. the method consists in chemical biotinylation of antigen-bound antibodies in a well of elisa plate. using as an example target vaccinia virus a27l protein it was shown that the yield of biotinylated reactant is enough to set comprehensive sandwich elisa for a moderate size panel of up to 25 monoclonal antibo ... | 2015 | 26615636 |
| hydrodynamic gene delivery of cc chemokine binding fc fusion proteins to target acute vascular inflammation in vivo. | blockade of cc chemokines is an attractive yet under utilized therapeutic strategy. we report the in vivo pharmacokinetics of a broad-spectrum vaccinia virus cc chemokine binding protein (35 k) fused to human igg1 fc. we demonstrate that the in vivo efficacy of the protein can be interrogated using hydrodynamic gene delivery of a standard mammalian expression plasmid. high plasma levels of the 35 k-fc protein are maintained for at least 14 days post gene transfer, with the protein still detectab ... | 2015 | 26620767 |
| toxicity and antiviral activity of the extracts of submerged mycelium of nematophagous duddingtonia flagrans fungus in vero cell culture. | we studied toxicity and antiviral activity of aqueous and ethanol extracts of bioactive substances from the biomass of nematophagous fungus duddingtonia flagrans prepared by submerged culturing of the mycelium. it is found that both extracts were characterized by low toxicity for cultured vero cells and inhibited reproduction of dna-viruses in this cell line. ethanol extract of the fungus exhibited higher in vitro antiviral activity against herpes simplex virus type 2, ectromelia virus, and vacc ... | 2015 | 26621278 |
| wham: identifying structural variants of biological consequence. | existing methods for identifying structural variants (svs) from short read datasets are inaccurate. this complicates disease-gene identification and efforts to understand the consequences of genetic variation. in response, we have created wham (whole-genome alignment metrics) to provide a single, integrated framework for both structural variant calling and association testing, thereby bypassing many of the difficulties that currently frustrate attempts to employ svs in association testing. here ... | 2015 | 26625158 |
| aim2 inflammasome in infection, cancer, and autoimmunity: role in dna sensing, inflammation, and innate immunity. | recognition of dna by the cell is an important immunological signature that marks the initiation of an innate immune response. aim2 is a cytoplasmic sensor that recognizes dsdna of microbial or host origin. upon binding to dna, aim2 assembles a multiprotein complex called the inflammasome, which drives pyroptosis and proteolytic cleavage of the proinflammatory cytokines pro-il-1β and pro-il-18. release of microbial dna into the cytoplasm during infection by francisella, listeria, mycobacterium, ... | 2015 | 26626159 |
| vaccinia virus as a subhelper for aav replication and packaging. | adeno-associated virus (aav) has been widely used as a gene therapy vector to treat a variety of disorders. while these vectors are increasingly popular and successful in the clinic, there is still much to learn about the viruses. understanding the biology of these viruses is essential in engineering better vectors and generating vectors more efficiently for large-scale use. aav requires a helper for production and replication making this aspect of the viral life cycle crucial. vaccinia virus (v ... | 2015 | 26636113 |
| tailoring a combination preerythrocytic malaria vaccine. | the leading malaria vaccine candidate, rts,s, based on the plasmodium falciparum circumsporozoite protein (csp), will likely be the first publicly adopted malaria vaccine. however, this and other subunit vaccines, such as virus-vectored thrombospondin-related adhesive protein (trap), provide only intermediate to low levels of protection. in this study, the plasmodium berghei homologues of antigens csp and trap are combined. trap is delivered using adenovirus- and vaccinia virus-based vectors in ... | 2015 | 26667840 |
| clinical development of ebola vaccines. | the ongoing outbreak of ebola virus disease in west africa highlighted the lack of a licensed drug or vaccine to combat the disease and has renewed the urgency to develop a pipeline of ebola vaccines. a number of different vaccine platforms are being developed by assessing preclinical efficacy in animal models and expediting clinical development. over 15 different vaccines are in preclinical development and 8 vaccines are now in different stages of clinical evaluation. these vaccines include dna ... | 2015 | 26668751 |
| an orthopoxvirus-based vaccine reduces virus excretion after mers-cov infection in dromedary camels. | middle east respiratory syndrome coronavirus (mers-cov) infections have led to an ongoing outbreak in humans, which was fueled by multiple zoonotic mers-cov introductions from dromedary camels. in addition to the implementation of hygiene measures to limit further camel-to-human and human-to-human transmissions, vaccine-mediated reduction of mers-cov spread from the animal reservoir may be envisaged. here we show that a modified vaccinia virus ankara (mva) vaccine expressing the mers-cov spike p ... | 2016 | 26678878 |
| mutations in the leucine zipper-like motif of the human parainfluenza virus 3 fusion protein impair fusion activity. | to investigate the effect of the leucine zipper-like motif between hra and hrb of the human parainfluenza virus 3 fusion protein on fusion activity. | 2015 | 26694747 |