Publications
| Title | Abstract | Year Filter | PMID(sorted descending) Filter |
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| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| decoding poxvirus genome. | 2015 | 26429864 | |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| [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 |
| oncolytic viruses: from bench to bedside with a focus on safety. | oncolytic viruses are a relatively new class of anti-cancer immunotherapy agents. several viruses have undergone evaluation in clinical trials in the last decades, and the first agent is about to be approved to be used as a novel cancer therapy modality. in the current review, an overview is presented on recent (pre)clinical developments in the field of oncolytic viruses that have previously been or currently are being evaluated in clinical trials. special attention is given to possible safety i ... | 2015 | 25996182 |
| modification of promoter spacer length in vaccinia virus as a strategy to control the antigen expression. | vaccinia viruses (vacvs) with distinct early promoters have been developed to enhance antigen expression and improve antigen-specific cd8 t-cell responses. it has not been demonstrated how the length of the spacer between the coding region of the gene and its regulatory early promoter motif influences antigen expression, and whether the timing of gene expression can modify the antigen-specific cd4 t-cell response. we generated several recombinant vacvs based on the attenuated modified vaccinia a ... | 2015 | 25972354 |
| 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 |
| characterization of hiv-1 entry inhibitors with broad activity against r5 and x4 viral strains. | combined antiretroviral therapy has drastically reduced mortality and morbidity of hiv-infected individuals. nevertheless long-term toxicity and appearance of viral resistance hampers the prolonged effectiveness of combination therapy, requiring a continuous input of drugs to replace those utilized in combination regimens. we here investigated the anti-hiv activity of novel derivatives of the suradista chemical class. | 2015 | 25888743 |
| cardiac safety of modified vaccinia ankara for vaccination against smallpox in a young, healthy study population. | conventional smallpox vaccines based on replicating vaccinia virus (vv) strains (e.g. lister elstree, nycboh) are associated with a high incidence of myo-/pericarditis, a severe inflammatory cardiac complication. a new smallpox vaccine candidate based on a non-replicating modified vaccinia ankara (mva) poxvirus has been assessed for cardiac safety in a large placebo-controlled clinical trial. | 2015 | 25879867 |
| 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 |
| vaccinia virus infection requires maturation of macropinosomes. | the prototypic poxvirus, vaccinia virus (vacv), occurs in two infectious forms, mature virions (mvs) and extracellular virions (evs). both enter hela cells by inducing macropinocytic uptake. using confocal microscopy, live-cell imaging, targeted rnai screening and perturbants of endosome maturation, we analyzed the properties and maturation pathway of the macropinocytic vacuoles containing vacv mvs in hela cells. the vacuoles first acquired markers of early endosomes [rab5, early endosome antige ... | 2015 | 25869659 |
| [a novel immunization strategy to induce strong humoral responses against hiv-1 using combined dna, recombinant vaccinia virus and protein vaccines]. | to optimize the immunization strategy against hiv-1, a dna vaccine was combined with a recombinant vaccinia virus (rtv) vaccine and a protein vaccine. immune responses against hiv-1 were detected in 30 female guinea pigs divided into six groups. three groups of guinea pigs were primed with hiv-1 dna vaccine three times, boosted with rtv at week 14, and then boosted with gp140 protein at intervals of 4, 8 or 12 weeks. simultaneously, the other three groups of animals were primed with rtv vaccine ... | 2014 | 25868279 |
| 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 |
| the evolution of poxvirus vaccines. | after edward jenner established human vaccination over 200 years ago, attenuated poxviruses became key players to contain the deadliest virus of its own family: variola virus (varv), the causative agent of smallpox. cowpox virus (cpxv) and horsepox virus (hspv) were extensively used to this end, passaged in cattle and humans until the appearance of vaccinia virus (vacv), which was used in the final campaigns aimed to eradicate the disease, an endeavor that was accomplished by the world health or ... | 2015 | 25853483 |
| hiv-1 vaccines based on replication-competent tiantan vaccinia protected chinese rhesus macaques from simian hiv infection. | to assess the efficacy of hiv vaccines constructed from replication-competent tiantan vaccinia virus (rtv) alone or combined with dna in protecting chinese rhesus macaques from homologous simian/human immunodeficiency virus (shiv)-cn97001 challenge. | 2015 | 25849828 |
| 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 |
| hiv specific responses induced in nonhuman primates with anrs hiv-lipo-5 vaccine combined with rmva-hiv prime or boost immunizations. | we evaluated the immunogenicity of a prime/boost vaccine strategy combining 5 lipopeptides (hiv-lipo-5) and a recombinant modified vaccinia virus ankara (rmva-hiv) in cynomolgus macaques. both of these vaccine components deliver hiv lai gag, pol, and nef antigens. systemic and local safety was excellent in all groups. immunization with hiv-lipo-5 alone induced significant serum anti-hiv antibody titers which were not modified by rmva-hiv immunization. however, induction of t-cell responses, as m ... | 2015 | 25839103 |
| oncolytic poxviruses. | current standard treatments of cancer can prolong survival of many cancer patients but usually do not effectively cure the disease. oncolytic virotherapy is an emerging therapeutic for the treatment of cancer that exploits replication-competent viruses to selectively infect and destroy cancerous cells while sparing normal cells and tissues. clinical and/or preclinical studies on oncolytic viruses have revealed that the candidate viruses being tested in trials are remarkably safe and offer potent ... | 2014 | 25839047 |
| evaluation of non-reciprocal heterologous immunity between unrelated viruses. | heterologous immunity refers to the phenomenon whereby a history of an immune response against one pathogen can provide a level of immunity to a second unrelated pathogen. previous investigations have shown that heterologous immunity is not necessarily reciprocal, such as in the case of vaccinia virus (vacv). replication of vacv is reduced in mice immune to a variety of pathogens, while vacv fails to induce immunity to several of the same pathogens, including lymphocytic choriomeningitis virus ( ... | 2015 | 25838115 |
| protective efficacy of the conserved np, pb1, and m1 proteins as immunogens in dna- and vaccinia virus-based universal influenza a virus vaccines in mice. | the conventional hemagglutinin (ha)- and neuraminidase (na)-based influenza vaccines need to be updated most years and are ineffective if the glycoprotein ha of the vaccine strains is a mismatch with that of the epidemic strain. universal vaccines targeting conserved viral components might provide cross-protection and thus complement and improve conventional vaccines. in this study, we generated dna plasmids and recombinant vaccinia viruses expressing the conserved proteins nucleoprotein (np), p ... | 2015 | 25834017 |
| cleavage of dicer protein by i7 protease during vaccinia virus infection. | dicer is the key component in the mirna pathway. degradation of dicer protein is facilitated during vaccinia virus (vv) infection. a c-terminal cleaved product of dicer protein was detected in the presence of mg132 during vv infection. thus, it is possible that dicer protein is cleaved by a viral protease followed by proteasome degradation of the cleaved product. there is a potential i7 protease cleavage site in the c-terminus of dicer protein. indeed, reduction of dicer protein was detected whe ... | 2015 | 25815818 |
| 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 |
| molecular genetic analysis of orf virus: a poxvirus that has adapted to skin. | orf virus is the type species of the parapoxvirus genus of the family poxviridae. it induces acute pustular skin lesions in sheep and goats and is transmissible to humans. the genome is g+c rich, 138 kbp and encodes 132 genes. it shares many essential genes with vaccinia virus that are required for survival but encodes a number of unique factors that allow it to replicate in the highly specific immune environment of skin. phylogenetic analysis suggests that both viral interleukin-10 and vascular ... | 2015 | 25807056 |
| one-step duplex polymerase chain reaction for the detection of swinepox and vaccinia viruses in skin lesions of swine with poxvirus-related disease. | infection of pigs with swinepox virus (swpv) was reported in brazil in 2011. swpv causes a systemic pustular disease in pigs and the symptoms are clinically indistinguishable from those caused by vaccinia virus (vacv) infection. pigs infected with vacv have been reported in various countries; however, vacv is endemic in brazil, india and other countries, where it affects mainly dairy cows, dairy buffaloes and dairy workers causing localized pustules. the transmission of vacv to other susceptible ... | 2015 | 25804245 |
| 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 |
| immunogenicity and virulence of attenuated vaccinia virus tian tan encoding hiv-1 muti-epitope genes, p24 and cholera toxin b subunit in mice. | no effective prophylactic or therapeutic vaccine against hiv-1 in humans is currently available. this study analyzes the immunogenicity and safety of a recombinant attenuated vaccinia virus. a chimeric gene of hiv-1 multi-epitope genes containing cpg odn and cholera toxin b subunit (ctb) was inserted into chinese vaccinia virus tian tan strain (vtt) mutant strain. the recombinant virus rddvtt(-ccmp24) was assessed for immunogenicity and safety in mice. results showed that the protein ccmp24 was ... | 2015 | 25796990 |
| 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 |