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interplay between modified vaccinia virus ankara and dendritic cells: phenotypic and functional maturation of bystander dendritic cells.modified vaccinia virus ankara (mva) is an attenuated poxvirus strain, currently under evaluation as a vaccine vector in various clinical settings. it has been reported that human dendritic cells (dcs) mature after infection with mva, but reports on the functionality of dcs have so far been controversial. in this work, we studied the phenotype and functionality of mva-infected dcs. as previously reported, we found that human monocyte-derived dcs upregulated cd86 and hla-dr in response to mva inf ...201121411535
sequential therapy with jx-594, a targeted oncolytic poxvirus, followed by sorafenib in hepatocellular carcinoma: preclinical and clinical demonstration of combination efficacy.jx-594 is a targeted and granulocyte-macrophage colony stimulating factor (gm-csf) expressing oncolytic poxvirus designed to selectively replicate in and destroy cancer cells through viral oncolysis and tumor-specific immunity. in a phase 1 trial, jx-594 injection into hepatocellular carcinoma (hcc) was well-tolerated and associated with viral replication, decreased tumor perfusion, and tumor necrosis. we hypothesized that jx-594 and sorafenib, a small molecule inhibitor of b-raf and vascular en ...201121427706
clinical development directions in oncolytic viral therapy.oncolytic virotherapy is an emerging experimental treatment platform for cancer therapy. oncolytic viruses are replicative-competent viruses that are engineered to replicate selectively in cancer cells with specified oncogenic phenotypes. multiple dna and rna viruses have been clinically tested in a variety of tumors. this review will provide a brief description of these novel anticancer biologics and will summarize the results of clinical investigation. to date oncolytic virotherapy has shown t ...201121436867
rapid detection of anti-vaccinia virus neutralizing antibodies.increasing infections with monkeypox and cowpox viruses pose a continuous and growing threat to human health. the standard method for detecting poxvirus neutralizing antibodies is the plaque-reduction neutralization test that is specific but also time-consuming and laborious. therefore, a rapid and reliable method was developed to determine neutralizing antibody titers within twelve hours. the new assay measures viral mrna transcription as a marker for actively replicating virus after incomplete ...201121439060
evaluation of imiquimod for topical treatment of vaccinia virus cutaneous infections in immunosuppressed hairless mice.imiquimod is an immune response modifier prescribed as a topical medication for a number of viral and neoplastic conditions. we evaluated the antiviral activity of imiquimod against vaccinia virus (wr strain) cutaneous infections in immunosuppressed (with cyclophosphamide) hairless mice when administered after virus exposure. primary lesions progressed in severity, satellite lesions developed, and infection eventually killed the mice. once daily topical treatment with 1% imiquimod cream for 3, 4 ...201121439326
b cell-specific expression of b7-2 is required for follicular th cell function in response to vaccinia virus.follicular th (t(fh)) cells are specialized in provision of help to b cells that is essential for promoting protective ab responses. cd28/b7 (b7-1 and b7-2) interactions are required for germinal center (gc) formation, but it is not clear if they simply support activation of naive cd4 t cells during initiation of responses by dendritic cells or if they directly control t(fh) cells and/or directly influence follicular b cell differentiation. using a model of vaccinia virus infection, we show that ...201121441451
mva and nyvac as vaccines against emergent infectious diseases and cancer.recombinants based on poxviruses have been used extensively as gene delivery systems to study many biological functions of foreign genes and as vaccines against many pathogens, particularly in the veterinary field. based on safety record, efficient expression and ability to trigger specific immune responses, two of the most promising poxvirus vectors for human use are the attenuated modified vaccinia virus ankara (mva) and the copenhagen derived nyvac strains. because of the scientific and clini ...201121453284
insertion of the human sodium iodide symporter to facilitate deep tissue imaging does not alter oncolytic or replication capability of a novel vaccinia virus.oncolytic viruses show promise for treating cancer. however, to assess therapeutic efficacy and potential toxicity, a noninvasive imaging modality is needed. this study aimed to determine if insertion of the human sodium iodide symporter (hnis) cdna as a marker for non-invasive imaging of virotherapy alters the replication and oncolytic capability of a novel vaccinia virus, glv-1h153.201121453532
dual neonate vaccine platform against hiv-1 and m. tuberculosis.acquired immunodeficiency syndrome and tuberculosis (tb) are two of the world's most devastating diseases. the first vaccine the majority of infants born in africa receive is mycobacterium bovis bacillus calmette-guérin (bcg) as a prevention against tb. bcg protects against disseminated disease in the first 10 years of life, but provides a variable protection against pulmonary tb and enhancing boost delivered by recombinant modified vaccinia virus ankara (rmva) expressing antigen 85a (ag85a) of ...201121603645
concerted antigen processing of a short viral antigen by human caspase-5 and -10.the generation of peptides presented by mhc class i molecules requires the proteolytic activity of the proteasome and/or other peptidases. the processing of a short vaccinia virus-encoded antigen can take place by a proteasome-independent pathway involving initiator caspase-5 and -10, which generate antigenic peptides recognized by cd8(+) t lymphocytes. in the present study, comparing single versus double enzyme digestions by mass spectrometry analysis, both qualitative and quantitative differen ...201121454616
human atopic dermatitis complicated by eczema herpeticum is associated with abnormalities in ifn-? response.the basis for increased susceptibility of patients with atopic dermatitis (ad) to develop disseminated viral skin infections such as eczema herpeticum (ad with a history of eczema herpeticum, adeh(+)) is poorly understood.201121458658
cowpox virus isolate virulent in humans shows attenuated phenotype in mice.we have cultured cowpox virus (cpxv) from skin lesion material of a human patient from austria. phylogenetic comparison of the ha-gene revealed a rather homogeneous cluster with other local isolates from recent years, the a36r-gene was mostly related to elephant derived strains from germany. despite causing disease in human, the isolate at/carinthia/788/07 surprisingly even at high titers showed a highly reduced virulence in balb/c mice upon intranasal inoculation as compared to vaccinia virus. ...201121463881
immunization with hiv gag targeted to dendritic cells followed by recombinant new york vaccinia virus induces robust t-cell immunity in nonhuman primates.protein vaccines, if rendered immunogenic, would facilitate vaccine development against hiv and other pathogens. we compared in nonhuman primates (nhps) immune responses to hiv gag p24 within 3g9 antibody to dec205 ("dec-hiv gag p24"), an uptake receptor on dendritic cells, to nontargeted protein, with or without poly iclc, a synthetic double stranded rna, as adjuvant. priming s.c. with 60 µg of both hiv gag p24 vaccines elicited potent cd4(+) t cells secreting il-2, ifn-?, and tnf-a, which also ...201121467219
orthopoxvirus dna in eurasian lynx, sweden.cowpox virus, which has been used to protect humans against smallpox but may cause severe disease in immunocompromised persons, has reemerged in humans, domestic cats, and other animal species in europe. orthopoxvirus (opv) dna was detected in tissues (lung, kidney, spleen) in 24 (9%) of 263 free-ranging eurasian lynx (lynx lynx) from sweden. thymidine kinase gene amplicon sequences (339 bp) from 21 lynx were all identical to those from cowpox virus isolated from a person in norway and phylogene ...201121470451
mapping the i{kappa}b kinase {beta} (ikk{beta})-binding interface of the b14 protein, a vaccinia virus inhibitor of ikk{beta}-mediated activation of nuclear factor {kappa}b.the iκb kinase (ikk) complex regulates activation of nf-κb, a critical transcription factor in mediating inflammatory and immune responses. not surprisingly, therefore, many viruses seek to inhibit nf-κb activation. the vaccinia virus b14 protein contributes to virus virulence by binding to the ikkβ subunit of the ikk complex and preventing nf-κb activation in response to pro-inflammatory stimuli. previous crystallographic studies showed that the b14 protein has a bcl-2-like fold and forms homod ...201121474453
rna helicase retinoic acid-inducible gene i (rig-i) as a sensor of hantaan virus (htnv) replication.hantaan virus (htnv) causes severe human disease. the htnv genome consists of three ssrna segments of negative polarity which are complexed with viral nucleocapsid (n) protein. how the human innate immune system detects htnv is unclear. rna heli-case retinoic acid-inducible gene i (rig-i) does not sense genomic htnv rna. so far it has not been analyzed whether pathogen associated molecular patterns (pamps) gen-erated during the htnv replication trigger rig-i-mediated innate responses. indeed, we ...201121632559
different patterns of expansion, contraction and memory differentiation of hiv-1 gag-specific cd8 t cells elicited by adenovirus type 5 and modified vaccinia ankara vaccines.the magnitude and functional quality of antiviral cd8 t cell responses are critical for the efficacy of t cell based vaccines. here, we investigate the influence of two popular viral vectors, adenovirus type 5 (ad5) and modified vaccinia ankara (mva), on expansion, contraction and memory differentiation of hiv-1 gag insert-specific cd8 t cell responses following immunization and show different patterns for the two recombinant viral vectors. the ad5 vector primed 6-fold higher levels of insert-sp ...201121651938
genome-wide analysis of the 5' and 3' ends of vaccinia virus early mrnas delineates regulatory sequences of annotated and anomalous transcripts.poxviruses are large dna viruses that encode a multisubunit rna polymerase, stage-specific transcription factors, and enzymes that cap and polyadenylate mrnas within the cytoplasm of infected animal cells. genome-wide microarray and rna-seq technologies have been used to profile the transcriptome of vaccinia virus (vacv), the prototype member of the family. here, we adapted tag-based methods in conjunction with solid and illumina deep sequencing platforms to determine the precise 5' and 3' ends ...201121490097
a genetically humanized mouse model for hepatitis c virus infection.hepatitis c virus (hcv) remains a major medical problem. antiviral treatment is only partially effective and a vaccine does not exist. development of more effective therapies has been hampered by the lack of a suitable small animal model. although xenotransplantation of immunodeficient mice with human hepatocytes has shown promise, these models are subject to important challenges. building on the previous observation that cd81 and occludin comprise the minimal human factors required to render mo ...201121654804
synthesis, metabolic stability and antiviral evaluation of various alkoxyalkyl esters of cidofovir and 9-(s)-[3-hydroxy-2-(phosphonomethoxy)propyl]adenine.alkoxyalkyl esters of cidofovir (cdv) are orally active agents which inhibit the replication of a variety of double stranded dna (dsdna) viruses including variola, vaccinia, ectromelia, herpes simplex virus, cytomegalovirus, adenovirus and others. one of these compounds, hexadecyloxypropyl-cdv (hdp-cdv, cmx001) is in clinical development for prevention and treatment of poxvirus infection, vaccination complications, and for infections caused by cytomegalovirus, adenovirus, herpesviruses and other ...201121493074
enhancement of immune response to an antigen delivered by vaccinia virus by displaying the antigen on the surface of intracellular mature virion.vaccinia virus (vacv) is the vaccine for smallpox and a widely used vaccine vector for infectious diseases and cancers. the majority of the antibodies elicited by live vacv vaccination respond to virion structural proteins, including many integral membrane proteins on the intracellular mature virion (mv). here, we showed that antibody response to an exogenous antigen delivered by vacv was greatly enhanced by incorporating the antigen as an integral membrane protein of mv. we constructed recombin ...201121664218
an efficient method for generating poxvirus recombinants in the absence of selection.the use of selectable markers (ecogpt) and selection pressures to aid in detection of poxvirus (vaccinia, vv) recombinants has been implicated in the unintended introduction of second site mutations. we have reinvestigated the use of the helper virus system described by scheiflinger et al. [1] and adapted by yao and evans [2] which produces recombinants at a high frequency in the absence of any selection, at a rate of 6-100%. our system uses fowlpox virus (fpv) as the infectious helper virus whi ...201121494427
immunogenicity in mice and rhesus monkeys vaccinated with recombinant vaccinia virus expressing bivalent e7e6 fusion proteins from human papillomavirus types 16 and 18.persistent infection with high-risk human papillomavirus (hpv) is a predominant cause of cervical cancer, and hpv16 and hpv18 occur in 50% and 20% of cervical cancer cases, respectively. the viral oncogenes e6 and e7 are constitutively expressed by hpv-associated tumour cells and can therefore be used as target antigens for immunotherapy. in this study, we constructed a recombinant vaccinia virus co-expressing the hpv16/18 e7e6 fusion proteins (rvvj16/18e7e6) for use as a therapeutic vaccine for ...201121672263
distinctive tlr7 signaling, type i ifn production, and attenuated innate and adaptive immune responses to yellow fever virus in a primate reservoir host.why cross-species transmissions of zoonotic viral infections to humans are frequently associated with severe disease when viruses responsible for many zoonotic diseases appear to cause only benign infections in their reservoir hosts is unclear. sooty mangabeys (sms), a reservoir host for siv, do not develop disease following siv infection, unlike nonnatural hiv-infected human or siv-infected rhesus macaque (rm) hosts. siv infections of sms are characterized by an absence of chronic immune activa ...201121515797
programmed death 1 regulates development of central memory cd8 t cells after acute viral infection.the t cell response possesses a number of inhibitory receptors to regulate the extent of the antiviral response and prevent immune pathology. these receptors are generally transiently upregulated during an effector response and then downregulated during memory. some inhibitory receptors, such as programmed death 1 (pd-1) and lag-3, were shown to be aberrantly upregulated during memory to chronic lymphocytic choriomeningitis virus infection, limiting functional capabilities. however, little is kn ...201121525385
an epitope conserved in orthopoxvirus a13 envelope protein is the target of neutralizing and protective antibodies.primary immunization of humans with smallpox vaccine (live vaccinia virus (vacv)) consistently elicits antibody responses to six vacv virion membrane proteins, including a13. however, whether anti-a13 antibody contributes to immune protection against orthopoxviruses was unknown. here, we isolated a murine monoclonal antibody (mab) against a13 from a mouse that had been infected with vacv. the anti-a13 mab bound to recombinant a13 protein with an affinity of 3.4nm and neutralized vacv mature viri ...201121810533
development of vaccinia reporter viruses for rapid, high content analysis of viral function at all stages of gene expression.vaccinia virus is the prototypical orthopoxvirus of poxviridae, a family of viruses that includes the human pathogens variola (smallpox) and monkeypox. core viral functions are conserved among orthopoxviruses, and consequently vaccinia is routinely used to study poxvirus biology and screen for novel antiviral compounds. here we describe the development of a series of fluorescent protein-based reporter vaccinia viruses that provide unprecedented resolution for tracking viral function. the reporte ...201121569797
vaccinia virus as a vaccine delivery system for marsupial wildlife.vaccines based on recombinant poxviruses have proved successful in controlling diseases such as rabies and plague in wild eutherian mammals. they have also been trialled experimentally as delivery agents for fertility-control vaccines in rodents and foxes. in some countries, marsupial mammals represent a wildlife disease reservoir or a threat to conservation values but, as yet there has been no bespoke study of efficacy or immunogenicity of a poxvirus-based vaccine delivery system in a marsupial ...201121570435
disabling complement regulatory activities of vaccinia virus complement control protein reduces vaccinia virus pathogenicity.poxviruses encode a repertoire of immunomodulatory proteins to thwart the host immune system. one among this array is a homolog of the host complement regulatory proteins that is conserved in various poxviruses including vaccinia (vacv) and variola. the vaccinia virus complement control protein (vcp), which inhibits complement by decaying the classical pathway c3-convertase (decay-accelerating activity), and by supporting inactivation of c3b and c4b by serine protease factor i (cofactor activity ...201121803094
adverse events post smallpox-vaccination: insights from tail scarification infection in mice with vaccinia virus.adverse events upon smallpox vaccination with fully-replicative strains of vaccinia virus (vacv) comprise an array of clinical manifestations that occur primarily in immunocompromised patients leading to significant host morbidity/mortality. the expansion of immune-suppressed populations and the possible release of variola virus as a bioterrorist act have given rise to concerns over vaccination complications should more widespread vaccination be reinitiated. our goal was to evaluate the componen ...201121526210
[the non-replicating recombinant vaccinia virus expressing six genes of hiv-1 can be passaged stably in cef].to investigate the genetic stability (including the vector of vaccinia virus and six foreign genes: gp160, gag, pol, rev, tat and nef) of the hiv-1 non-replicating recombinant vaccinia virus (rntv-c). rntv-c was serially passaged to passage 25 (p25) in primary chicken embryo fibroblast (cef). p9, p12, p15 and p25 were selected to study the genetic stability in four aspects, including the genetic stability of viral vector, the genetic stability of six foreign genes, the expressing stability of fo ...201121528538
synthesis, antiviral and cytotoxic investigation of 2-phenyl-3-substituted quinazolin-4(3h)-ones.a series of 3(benzylideneamino)-2-phenyl quinazoline-4(3h)-ones was synthesized by reaction of 3-amino-2-phenyl-3h-quinazoline-4-one with various carbonyl compounds.201121796872
expression profiling of the intermediate and late stages of poxvirus replication.the double-stranded dna genome of vaccinia virus (vacv), the prototype poxvirus, contains approximately 200 open reading frames (orfs) that are transcribed at early, intermediate and late stages of infection. previous high throughput deep rna-sequencing allowed us to map 118 vacv early genes that are expressed before viral dna replication and 93 post-replicative genes. however, the intermediate and late stage post-replicative genes could not be differentiated. here, we synchronized infections wi ...201121795349
vaccinia extracellular virions enter cells by macropinocytosis and acid-activated membrane rupture.vaccinia virus (vacv), the model poxvirus, produces two types of infectious particles: mature virions (mvs) and extracellular virions (evs). ev particles possess two membranes and therefore require an unusual cellular entry mechanism. by a combination of fluorescence and electron microscopy as well as flow cytometry, we investigated the cellular processes that evs required to infect hela cells. we found that ev particles were endocytosed, and that internalization and infection depended on actin ...201121792173
impaired cellular responses to cytosolic dna or infection with listeria monocytogenes and vaccinia virus in the absence of the murine lgp2 protein.innate immune signaling is crucial for detection of and the initial response to microbial pathogens. evidence is provided indicating that lgp2, a dexh box domain protein related to the rna recognition receptors rig-i and mda5, participates in the cellular response to cytosolic double-stranded dna (dsdna). analysis of embryonic fibroblasts and macrophages from mice harboring targeted disruption in the lgp2 gene reveals that lgp2 can act as a positive regulator of type i ifn and anti-microbial gen ...201121533147
use of a negative selectable marker for rapid selection of recombinant vaccinia virus.vaccinia virus has been a powerful tool in molecular biology and vaccine development. the relative ease of inserting and expressing foreign genes combined with its broad host range has made it an attractive antigen delivery system against many heterologous diseases. many different approaches have been developed to isolate recombinant vaccinia virus generated from homologous recombination; however, most are time-consuming, often requiring a series of passages or specific cell lines. herein we int ...201121548892
evaluation of the role of the vaccinia virus uracil dna glycosylase and a20 proteins as intrinsic components of the dna polymerase holoenzyme.the vaccinia virus dna polymerase (pol) is inherently distributive, but acquires processivity by associating with a heterodimeric processivity factor comprised of the viral a20 and d4 proteins. d4 is also an enzymatically active uracil dna glycosylase (udg). the presence of an active repair protein as an essential component of the polymerase holoenzyme is a unique feature of the replication machinery. we have shown previously that the a20:udg complex has a stoichiometry of ~ 1:1 and our data sug ...201121572084
benzylidene-bis-(4-hydroxycoumarin) and benzopyrano-coumarin derivatives: synthesis, 1h/13c-nmr conformational and x-ray crystal structure studies and in vitro antiviral activity evaluations.we report on the synthesis of 4-hydroxycoumarin dimers 1-15 bearing an aryl substituent on the central linker and fused benzopyranocoumarin derivatives 16-20 and on their in vitro broad anti-dna and rna virus activity evaluations. the chemical identities and structure of compounds 1-20 were deduced from their homo- and heteronuclear nmr measurements whereas the conformational properties of 5, 14 and 20 were assessed by the use of 1d difference noe enhancements. unequivocal proof of the stereostr ...201121772234
action mechanisms of lithium chloride on cell infection by transmissible gastroenteritis coronavirus.transmissible gastroenteritis virus (tgev) is a porcine coronavirus. lithium chloride (licl) has been found to be effective against several dna viruses, such as herpes simplex virus and vaccinia virus. recently, we and others have reported the inhibitory effect of licl on avian infectious bronchitis coronavirus (ibv) infection, an rna virus. in the current study, the action mechanism of licl on cell infection by tgev was investigated. plaque assays and 3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-di-phe ...201121573100
role of sulfatide in vaccinia virus infection.background information: vaccinia virus (vacv) was used as a surrogate of variola virus (genus orthopoxvirus), the causative agent of smallpox, to study orthopoxvirus infection. vacv infects cells via attachment and fusion of the viral membrane with the host cell membrane. glycosphingolipids, expressed in multiple organs, are major components of lipid rafts and have been associated with the infectious route of several pathogens. results: we demonstrate that the vaccinia virus western reserve (vac ...201121554243
vaccinia virus lacking a17 induces complex membrane structures composed of open membrane sheets.the vaccinia virus (vacv) precursor membrane, the crescent, consists of an open membrane sheet and is formed by rupture of a cellular compartment. here, we asked whether a17, a viral membrane protein, plays a role in membrane rupture. without a17 synthesis, crescents are not formed, and instead, tubular and vesicular membranes accumulate (rodriguez et al. in j virol 69:4640-4648, 1). we used electron tomography (et) to analyze whether the viral membranes lacking a17 consist of open membrane shee ...201121590268
structural determinants of caspase-9 inhibition by the vaccinia virus protein, f1l.in multi-cellular organisms, apoptosis is a powerful method of host defense against viral infection. apoptosis is mediated by a cascade of caspase-family proteases that commit infected cells to a form of programmed cell death. therefore, in order to replicate within host cells, viruses have developed various strategies to inhibit caspase activation. in the mitochondrial cell-death pathway, release of cytochrome c from mitochondria into the cytosol triggers assembly of the oligomeric apoptosome, ...201121757755
differential effects of viral vectors on migratory afferent lymph dendritic cells in vitro predicts enhanced immunogenicity in vivo.targeting dendritic cells (dc) is key to driving effective immune responses. lymphatic cannulation provides access to the heterogeneous populations of dc draining peripheral sites in rodents and ruminants. afferent lymph dec-205(+)cd11c(+)sirpa(+) dc were preferentially infected ex vivo with three vaccine viral vectors: replication defective human adenovirus-5 (rhuadv5); modified vaccinia virus ankara (rmva) and fowlpox virus (rfpv) all expressing green fluorescent protein (gfp). the rhuadv5 inf ...201121752909
effect of human activated nras on replication of delns1 h5n1 influenza virus in mdck cells.abstract: background: ras, coded by ras proto-oncogenes, played an important role in signal transmission to regulate cell growth and differentiation. host activation of ras was significant for ifn-sensitive vaccinia virus (dele3l) or attenuate influenza virus in unallowable cells. results: huamn nras gene was activated by mutating in codon 61. then the activation of nras was detected by western blot in mdck cells. the delns1 h5n1 influenza virus with deletion of ns1 eif4gi binding domain was wea ...201121595878
lack of processing of the expressed orf1 gene product of hepatitis e virus.abstract: background: proteolytic processing is a common mechanism among plus strand rna viruses and the replicases of all plus strand rna viruses of animals thus far characterized undergo such processing. the replicase proteins of hepatitis e virus (hev) are encoded by orf1. a previous report published by our group [1] provided data that processing potentially occurred when orf1 (burmese strain; genotype 1) was expressed using a vaccinia virus-based expression system. findings: to further test ...201121595991
acyclic nucleoside phosphonates with a branched 2-(2-phosphonoethoxy)ethyl chain: efficient synthesis and antiviral activity.series of novel acyclic nucleoside phosphonates (anps) with various nucleobases and 2-(2-phosphonoethoxy)ethyl (pee) chain bearing various substituents in ß-position to the phosphonate moiety were prepared. the influence of structural alternations on antiviral activity was studied. several derivatives exhibit antiviral activity against hiv and vaccinia virus (middle micromolar range), hsv-1 and hsv-2 (lower micromolar range) and vzv and cmv (nanomolar range), although the parent unbranched pee-a ...201121745746
characterization of immunologic properties of a second hla-a2 epitope from a granule protease in cml patients and hla-a2 transgenic mice.the serine proteases, neutrophil elastase (hne) and proteinase 3 (pr3), are aberrantly expressed in human myeloid leukemias. t-cell responses to these proteins have been correlated with remission in patients with chronic myeloid leukemia (cml). human pr3/hne-specific cd8(+) t cells predominantly recognize a nonameric hla-a2-restricted t-cell epitope called pr1 which is conserved in both ags. however, cml patients have cd8(+) t cells in peripheral blood recognizing an additional hla-a2 epitope te ...201121719601
viral quantitative capillary electrophoresis for counting intact viruses.the quantification of a virus plays an important role in vaccine development, clinical diagnostics, and environmental contamination assays. in all these cases, it is essential to calculate the concentration or number of intact virus particles (ivp) and estimate the degree of degradation and contamination of virus samples. in this work, we propose a cost-efficient, robust method for the quantification and characterization of intact viruses based on capillary zone electrophoresis. this separation ...201121599011
apoptosis and necrosis in vaccinia virus-infected hela g and bsc-40 cells.in most cells, vaccinia virus (vacv) infection is considered to cause a lytic cell death, an equivalent of necrosis. however, upon infection of the epithelial cell lines hela g and bsc-40 with vacv strain western reserve (wr), we have previously observed an increased activation of and activity attributable to caspases, a typical sign of apoptosis. in this paper, we have further analyzed the type of cell death in vacv-infected cells hela g and bsc-40. in a cell-based flow cytometric assay, we sho ...201121605605
vesicular stomatitis virus has extensive oncolytic activity against human sarcomas: rare resistance is overcome by blocking interferon pathways.oncolytic viruses have been tested against many carcinomas of ectodermal and endodermal origin; however, sarcomas, arising from mesoderm, have received relatively little attention. using 13 human sarcomas representing seven tumor types, we assessed the efficiency of infection, cytolysis, and replication of green fluorescent protein (gfp)-expressing vesicular stomatitis virus (vsv) and its oncolytically enhanced mutant vsv-rp30a. both viruses efficiently infected and killed 12 of 13 sarcomas. vsv ...201121734048
the interplay between ara+ºatuba virus and host signaling pathways: role of pi3k/akt in viral replication.in this study, we describe the interaction between ara+ºatuba virus (arav), a naturally occurring brazilian vaccinia virus isolated from an outbreak at a dairy farm, and the host cell's signal transduction pathways. even though arav infection led to phosphorylation of mapks mek/erk, jnk, and p38mapk, genetic or pharmacological inhibition of these pathways had no impact on viral replication. we also provide evidence that arav stimulated the phosphorylation of akt (pkb) at serine 473 (s473-p), a s ...201121735213
poxvirus a46 protein binds to tir domain-containing mal/tirap via an +¦-helical sub-domain.poxviruses are large dna viruses that replicate in the cytosol and express numerous proteins to subvert the host immunity. vaccinia virus a46 is a 25kda protein that antagonizes multiple components of the toll-like/interleukin-1 receptor (tlr) pathway by targeting cytosolic adaptor proteins. a46 binds to myd88, mal/tirap, trif and tram and suppresses the activation of nf-+¦b and interferon regulatory factors. each of these cytosolic adaptors has a tir domain that is critical for oligomerization ...201121831443
[the smallpox vaccines and the definitive destruction of the last virus strains.] 201121605878
a differential structure approach to membrane segmentation in electron tomography.electron tomography allows three-dimensional visualization of cellular landscapes in molecular detail. segmentation is a paramount stage for the interpretation of the reconstructed tomograms. although several computational approaches have been proposed, none has prevailed as a generic method and thus segmentation through manual annotation is still a common choice. in this work we introduce a segmentation method targeted at membranes, which define the natural limits of compartments within biologi ...201121616152
identification of cd8+ cytotoxic t lymphocyte epitopes from porcine reproductive and respiratory syndrome virus matrix protein in balb/c mice.abstract: twenty-seven nanopeptides derived from the matrix (m) protein of porcine reproductive and respiratory syndrome virus (prrsv) were screened for their ability to elicit a recall interferon-gamma (ifn-gamma) response from the splenocytes of balb/c mice following dna vaccination and a booster vaccination with recombinant vaccinia virus rwr-prrsv-m. we identified two peptides (amino acid residues k93fitsrcrl and f57gymtfvhf) as cd8+ cytotoxic t lymphocyte (ctl) epitopes. these peptides elic ...201121619712
synergistic anti-tumor effects between oncolytic vaccinia virus and paclitaxel are mediated by the ifn response and hmgb1.recent developments in the field of oncolytic or tumor-selective viruses have meant that the clinical applications of these agents are now being considered in more detail. like most cancer therapies it is likely that they will be used primarily in combination with other therapeutics. although several reports have shown that oncolytic viruses can synergize with chemotherapies within an infected cancer cell, it would be particularly important to determine whether factors released from infected cel ...201120739958
prime-boost vaccinations using recombinant flavivirus replicon and vaccinia virus vaccines: an elispot analysis.recombinant kunjin replicon virus-like particle (vlp), vaccinia virus (rvv) and dna vaccines were tested in a large series of prime-boost vaccinations using interferon (ifn)γ elispot assays that reflected effector (e), effector memory (em) and central memory (cm) responses. all vaccine constructs encoded the murine polytope immunogen and responses to four cd8 t-cell epitopes (tyqrtralv, syipsaeki, yphfmptnl and rpqasgvym) were measured. vlp/rvv out performed (by 14- to 20-fold) dna/rvv for induc ...201120680025
prevention of oxaliplatin-induced mechanical allodynia and neurodegeneration by neurotropin in the rat model.oxaliplatin is a key drug for colorectal cancer, but it causes acute peripheral neuropathy (triggered by cold) and chronic neuropathy (sensory and motor neuropathy) in patients. neurotropin, a non-protein extract from the inflamed rabbit skin inoculated with vaccinia virus, has been used to treat various chronic pains. in the present study, we investigated the effect of neurotropin on the oxaliplatin-induced neuropathy in rats. repeated administration of oxaliplatin caused cold hyperalgesia from ...201120829082
enhanced tumor therapy using vaccinia virus strain glv-1h68 in combination with a β-galactosidase-activatable prodrug seco-analog of duocarmycin sa.breast cancer is the most common cause of cancer-related death worldwide, thus remaining a crucial health problem among women despite advances in conventional therapy. therefore, new alternative strategies are needed for effective diagnosis and treatment. one approach is the use of oncolytic viruses for gene-directed enzyme prodrug therapy. here, the lacz-carrying vaccinia virus (vacv) strain glv-1h68 was used in combination with a β-galactosidase-activatable prodrug derived from a seco-analog o ...201120829890
5'oh dna breaks in apoptosis and their labeling by topoisomerase-based approach.recently, the concept of apoptotic cell elimination was expanded and programed cell death is no longer viewed as an individual cellular event. the complete description of the apoptotic process now includes two phases: the self-driven cell disassembly and the externally-controlled elimination of apoptotic cell corpses by phagocytizing cells. the second, phagocytic phase is essential, highly conserved, and is even more important than the internal phase of cell disassembly. this is because it ensur ...201121057922
activation of human dendritic cells by recombinant modified vaccinia virus ankara vectors encoding survivin and il-2 genes in vitro.modified vaccinia virus ankara (mva) has attracted significant attention as a safe, promising vector for immunotherapy. however, the precise effects of mva infection on immune responses in humans remain largely unknown. we constructed recombinant mva (rmva) encoding both a human tumor-associated antigen (survivin) and the proinflammatory cytokine interleukin (il)-2 and investigated their effects on human monocyte-derived dendritic cells (dcs). the results showed that infection with rmva slightly ...201019715401
the tumor-associated antigen 90k/mac-2-binding protein secreted by human colon carcinoma cells enhances extracellular levels of promatrilysin and is a novel substrate of matrix metalloproteinases-2, -7 (matrilysin) and -9: implications of proteolytic cleavage.the tumor-associated antigen 90k (taa90k)/mac-2-binding protein is expressed at elevated level in cancerous tissues and associated with poor prognosis. since taa90k has been implicated in the restructuring of the extracellular matrix, we examined the functional relationship between colon cancer cell-derived taa90k and the matrix metalloproteinase (mmp) promatrilysin (prommp-7), and also tested whether taa90k is a novel substrate for mmps-2, -7 and -9.201019665518
vaccinia virus complement control protein (vcp) improves kidney structure and function following ischemia/reperfusion injury in rats.renal transplantation is often confronted with ischemia reperfusion (i/r) injury that accounts for a delayed recovery of the graft. this surgically and biologically induced injury often results in activation of the complement system. the vaccinia virus complement control protein (vcp) down-regulates both the classical and alternative complement pathways by preventing the formation of c3b, a component where both pathways converge. the aim of the study was to investigate the effect of vcp on renal ...201019691975
partial protection against siv challenge by vaccination of adenovirus and mva vectors in rhesus monkeys.this study explores the effect of priming rhesus monkeys with an ad5/35 vector expressing simian immunodeficiency virus (siv) gag and gp120, and then boosting the animals with an modified vaccinia virus ankara (mva) vector encoding the same antigens after a 2-month interval. the animals were intravenously challenged with 100 tcid50 of highly pathogenic sivmac239 virus 2 months after the booster vaccination. the priming vaccination induced robust siv-specific cell-mediated and humoral immune resp ...201019759567
infection with viruses from several families triggers autoimmune diabetes in lew*1wr1 rats: prevention of diabetes by maternal immunization.the contribution of antecedent viral infection to the development of type 1 diabetes in humans is controversial. using a newer rat model of the disease, we sought to 1) identify viruses capable of modulating diabetes penetrance, 2) identify conditions that increase or decrease the diabetogenicity of infection, and 3) determine whether maternal immunization would prevent diabetes.201019794063
zoonotic poxviruses.poxviruses compromise a group of long known important pathogens including some zoonotic members affecting lifestock animals and humans. while whole genome sequence analysis started to shed light into the molecular mechanisms underlying host cell infection, viral replication as well as virulence, our understanding of poxvirus maintenance in nature and their transmission to humans is still poor. during the last two decades, reports on emerging human monkeypox outbreaks in africa and north america, ...201019828265
the poxvirus a35 protein is an immunoregulator.it was shown previously that the highly conserved vaccinia virus a35 gene is an important virulence factor in respiratory infection of mice. we show here that a35 is also required for full virulence by the intraperitoneal route of infection. a virus mutant in which the a35 gene has been removed replicated normally and elicited improved antibody, gamma interferon-secreting cell, and cytotoxic t-lymphocyte responses compared to wild-type virus, suggesting that a35 increases poxvirus virulence by i ...201019828608
requirement for formin-induced actin polymerization during spread of shigella flexneri.actin polymerization in the cytosol and at the plasma membrane is locally regulated by actin nucleators. several microbial pathogens exploit cellular actin polymerization to spread through tissue. the movement of the enteric pathogen shigella flexneri, both within the cell body and from cell to cell, depends on actin polymerization. during intercellular spread, actin polymerization at the bacterial surface generates protrusions of the plasma membrane, which are engulfed by adjacent cells. in the ...201019841078
the combination of marker gene swapping and fluorescence-activated cell sorting improves the efficiency of recombinant modified vaccinia virus ankara vaccine production for human use.modified vaccinia virus ankara (mva) is employed as a human vaccine vector for the high expression of heterologous genes and the lack of replication in mammalian cells. this study demonstrates that cells infected by recombinant viruses can be obtained by fluorescence-activated cell sorting. recombinant viruses are generated by a swapping event between a red fluorescent protein gene in the acceptor virus and a plasmid cassette coding for both a green fluorescent marker and a transgene. to prevent ...201019778556
application of proteomics methods for pathogen discovery.proteomics have been used widely to study proteins in complex materials such as cells, body fluids, tissues, and organisms. application of advance proteomic techniques for the characterization of disease-specific proteins may provide information for the detection of potential infectious agents. in this report, two proteomics techniques, a two-dimensional differential gel electrophoresis (2d-dige) and a one-dimensional gel electrophoresis and one-dimensional liquid chromatography coupled with mas ...201019751767
prime-boost immunization with adenoviral and modified vaccinia virus ankara vectors enhances the durability and polyfunctionality of protective malaria cd8+ t-cell responses.protection against liver-stage malaria relies on the induction of high frequencies of antigen-specific cd8+ t cells. we have previously reported high protective levels against mouse malaria, albeit short-lived, by a single vaccination with adenoviral vectors coding for a liver-stage antigen (me.trap). here, we report that prime-boost regimens using modified vaccinia virus ankara (mva) and adenoviral vectors encoding me.trap can enhance both short- and long-term sterile protection against malaria ...201019858306
concrete helix recalls smallpox win. 201021068812
a phase ii study of the cancer vaccine tg4010 alone and in combination with cytokines in patients with metastatic renal clear-cell carcinoma: clinical and immunological findings.muc1 over-expression in renal clear-cell carcinoma (rcc) is associated with poor prognosis. this phase ii study determined the efficacy and tolerability of tg4010, a cancer vaccine based on a modified vaccinia virus expressing muc1 and interleukin-2, in combination with cytokines, as first-line therapy in metastatic rcc. thirty-seven patients with progressive, muc1-positive rcc received tg4010 10(8) pfu/inj weekly for 6 weeks, then every 3 weeks until progression, when tg4010 was continued in co ...201021069322
variola and monkeypox viruses utilize conserved mechanisms of virion motility and release that depend on abl and src family tyrosine kinases.vaccinia virus (vacv) enters mammalian cells, replicates extranuclearly, and produces virions that move to the cell surface along microtubules, fuse with the plasma membrane, and move from infected cells toward apposing cells on actin-filled membranous protrusions or actin tails. to form actin tails, cell-associated enveloped virions (cev) require abl and src family tyrosine kinases. furthermore, release of cev from the cell requires abl but not src family tyrosine kinases and is blocked by imat ...201020962097
the vaccinia virus complement control protein modulates adaptive immune responses during infection.complement activation is an important component of the innate immune response against viral infection and also shapes adaptive immune responses. despite compelling evidence that complement activation enhances t cell and antibody (ab) responses during viral infection, it is unknown whether inhibition of complement by pathogens alters these responses. vaccinia virus (vacv) modulates complement activation by encoding a complement regulatory protein called the vaccinia virus complement control prote ...201021191012
esr and nmr studies provide evidence that phosphatidyl glycerol specifically interacts with poxvirus membranes.the lung would be the first organ targeted in case of the use of variola virus (the causative agent of smallpox) as a bioweapon. pulmonary surfactant composed of lipids (90%) and proteins (10%) is considered the major physiological barrier against airborne pathogens. the principle phospholipid components of lung surfactant were examined in an in vitro model to characterize their interactions with vacv, a surrogate for variola virus. one of them, dipalmitoyl phosphatidylglycerol (dppg), was recen ...201021194478
efficient lung recruitment of respiratory syncytial virus-specific th1 cells induced by recombinant bacillus calmette-guérin promotes virus clearance and protects from infection.infection by the respiratory syncytial virus (rsv) can cause extensive inflammation and lung damage in susceptible hosts due to a th2-biased immune response. such a deleterious inflammatory response can be enhanced by immunization with formalin- or uv-inactivated rsv, as well as with vaccinia virus expressing the rsv-g protein. recently, we have shown that vaccination with rbcg-expressing rsv ags can prevent the disease in the mouse. to further understand the immunological mechanisms responsible ...201021084664
update on the current status of cytomegalovirus vaccines.human cytomegalovirus (hcmv) is ubiquitous in all populations, and is the most commonly recognized cause of congenital viral infection in developed countries. on the basis of the economic costs saved and the improvement in quality of life that could potentially be conferred by a successful vaccine for prevention of congenital hcmv infection, the institute of medicine has identified hcmv vaccine development as a major public health priority. an effective vaccine could potentially also be benefici ...201021087108
lung surfactant dppg phospholipid inhibits vaccinia virus infection.vaccinia virus (vacv) was used as a surrogate of variola virus (genus orthopoxvirus), the causative agent of smallpox, to study orthopoxvirus infection via the respiratory airway. lung surfactant, a physiological barrier to infection encountered by the virus, is predominantly composed of phospholipids whose role during orthopoxvirus infection has not been investigated. an attenuated lister strain, derived from the traditional smallpox vaccine and the western reserve (wr) strain, lethal for mice ...201021095206
mig and the regulatory cytokines il-10 and tgf-β1 correlate with malaria vaccine immunogenicity and efficacy.malaria remains one of the world's greatest killers and a vaccine is urgently required. there are no established correlates of protection against malaria either for natural immunity to the disease or for immunity conferred by candidate malaria vaccines. the rts,s/as02a vaccine offers significant partial efficacy against malaria.mrna expression of five key cytokines interferon-gamma (ifn-γ), monokine induced by gamma (mig), interleukin-10 (il-10), transforming growth factor-β (tgf-β) and forkhead ...201020838432
third-generation smallpox vaccines: challenges in the absence of clinical smallpox.smallpox, a disease caused by variola virus, is estimated to have killed hundreds of millions to billions of people before it was certified as eradicated in 1980. however, there has been renewed interest in smallpox vaccine development due in part to zoonotic poxvirus infections and the possibility of a re-emergence of smallpox, as well as the fact that first-generation smallpox vaccines are associated with relatively rare, but severe, adverse reactions in some vaccinees. an understanding of the ...201020860482
il-15 increases the frequency of effector memory cd8+ t cells in rhesus monkeys immunized with hiv vaccine.several studies have suggested that interleukin (il)-15 is a promising adjuvant that promotes cellular immunity when administered with human immunodeficiency virus (hiv) vaccine. here we evaluated the effect of il-15 plasmid on hiv-specific immune responses, especially cellular immunity, in eight rhesus monkeys. these monkeys were immunized three times with hiv dna vaccine with or without il-15 plasmid and boosted with recombinant tiantan strain vaccinia virus-based hiv vaccine (rtv) 22 weeks af ...201020871629
an integrated approach to epitope analysis ii: a system for proteomic-scale prediction of immunological characteristics.abstract:201021044290
inhibition of poxvirus growth by terameprocol, a methylated derivative of nordihydroguaiaretic acid.terameprocol (tmp) is a methylated derivative of nordihydroguaiaretic acid, a phenolic antioxidant originally derived from creosote bush extracts. tmp has previously been shown to have antiviral and anti-inflammatory activities, and has been proven safe in phase i clinical trials conducted to evaluate tmp as both a topical and parenteral therapeutic. in the current study, we examined the ability of tmp to inhibit poxvirus growth in vitro, and found that tmp potently inhibited the growth of both ...201020888364
generation and characterization of a large panel of murine monoclonal antibodies against vaccinia virus.vaccinia virus (vacv), the vaccine for smallpox, induces an antibody response that is largely responsible for conferring protection. here, we studied the antibody response to vacv by generating and characterizing b cell hybridomas from a mouse immunized with vacv. antibodies from 66 hybridomas were found to recognize 11 vacv antigens (d8, a14, wr148, d13, h3, a56, a33, c3, b5, a10 and f13), 10 of which were previously recognized as major antigens in smallpox vaccine by a microarray of vacv prote ...201021056889
development of a highly efficacious vaccinia-based dual vaccine against smallpox and anthrax, two important bioterror entities.bioterrorism poses a daunting challenge to global security and public health in the 21st century. variola major virus, the etiological agent of smallpox, and bacillus anthracis, the bacterial pathogen responsible for anthrax, remain at the apex of potential pathogens that could be used in a bioterror attack to inflict mass casualties. although licensed vaccines are available for both smallpox and anthrax, because of inadequacies associated with each of these vaccines, serious concerns remain as ...201020921397
critical role for il-21 in both primary and memory anti-viral cd8+ t-cell responses.while it is well established that cd8(+) t cells generated in the absence of cd4(+) t cells mediate defective recall responses, the mechanism by which cd4(+) t cells confer help in the generation of cd8(+) t-cell responses remains poorly understood. to determine whether cd4(+) t-cell-derived il-21 is an important regulator of cd8(+) t-cell responses in help-dependent and -independent viral infections, we examined these responses in the il-21rα(-/-) mouse model. we show that il-21 has a role in p ...201021061439
nmr study of hydrogen exchange during the b-z transition of a dna duplex induced by the zα domains of yatapoxvirus e3l.the yaba-like disease viruses (yldv) are members of the yatapoxvirus family and have double-stranded dna genomes. the e3l protein, which is essential for pathogenesis in the vaccinia virus, consists of two domains: an n-terminal z-dna binding domain and a c-terminal rna binding domain. the crystal structure of the e3l orthologue of yldv (yabzα(e3l)) bound to z-dna revealed that the overall structure of yabzα(e3l) and its interaction with z-dna are very similar to those of hzα(adar1). here we hav ...201020937275
noncytotoxic inhibition of viral infection through eif4f-independent suppression of translation by 4egi-1.the eukaryotic initiation factor eif4f recruits ribosomes to capped mrnas while eif2 mediates start codon recognition to initiate protein synthesis. increasing interest in targeting translation to suppress tumor growth has led to the development of new classes of inhibitors, including 4egi-1, which disrupts eif4f complexes. however, the full effects of this inhibitor and its potential uses in the treatment of other disease states remain unclear. here, we show that overall rates of protein synthe ...201021068241
genetic analysis of murine hepatitis virus non-structural protein 16.mhv-wüts18 is an rna-negative, temperature-sensitive mutant of mouse coronavirus, strain murine hepatitis virus (mhv)-a59. we have previously identified the putative causal mutation of mhv-wüts18 as a c to u transition at codon 2446 in orf1b, which results in a substitution of proline 12 with serine in non-structural protein 16. here, we have used a vaccinia virus-based reverse genetic system to produce a recombinant virus, inf-mhv-wüts18((agc)) that encodes nsp16 serine 12 with agc rather than ...201020943891
nigericin is a potent inhibitor of the early stage of vaccinia virus replication.poxviruses remain a significant public health concern due to their potential use as bioterrorist agents and the spread of animal borne poxviruses, such as monkeypox virus, to humans. thus, the identification of small molecule inhibitors of poxvirus replication is warranted. vaccinia virus is the prototypic member of the orthopoxvirus genus, which also includes variola and monkeypox virus. in this study, we demonstrate that the carboxylic ionophore nigericin is a potent inhibitor of vaccinia viru ...201020951746
engineering recombinant poxviruses using a compact gfp-blasticidin resistance fusion gene for selection.recombinant poxviruses are important tools for research and some are candidate vaccines. to make these viruses a simple, small vector that can be used to engineer multiple strains of vaccinia virus and other model poxviruses, including ectromelia virus is of value. here a set of plasmids and methods for making these viruses that uses an enhanced green fluorescent protein-blasticidin resistance (gfp-bsd) fusion gene as a transient selectable marker are described. this gene is smaller than any of ...201021073901
cross-trial analysis of immunologic and clinical data resulting from phase i and ii trials of mva-5t4 (trovax) in colorectal, renal, and prostate cancer patients.the attenuated vaccinia virus mva has been engineered to deliver the tumor antigen 5t4 (mva-5t4; trovax), a surface glycoprotein expressed by most solid tumors. mva-5t4 has been tested in 2 phase i/ii and 7 phase ii clinical trials in colorectal (4 trials), renal (4 trials), and prostate (1 trial) advanced cancer patients. data have been collated from all 9 studies and used to investigate the magnitude and kinetics of 5t4-specific antibody responses after vaccination and to identify potential as ...201020948436
rnai screening for host factors involved in vaccinia virus infection using drosophila cells.viral pathogens represent a significant public health threat; not only can viruses cause natural epidemics of human disease, but their potential use in bioterrorism is also a concern. a better understanding of the cellular factors that impact infection would facilitate the development of much-needed therapeutics. recent advances in rna interference (rnai) technology coupled with complete genome sequencing of several organisms has led to the optimization of genome-wide, cell-based loss-of-functio ...201020834214
vaccinia virus d4 mutants defective in processive dna synthesis retain binding to a20 and dna.genome replication is inefficient without processivity factors, which tether dna polymerases to their templates. the vaccinia virus dna polymerase e9 requires two viral proteins, a20 and d4, for processive dna synthesis, yet the mechanism of how this tricomplex functions is unknown. this study confirms that these three proteins are necessary and sufficient for processivity, and it focuses on the role of d4, which also functions as a uracil dna glycosylase (udg) repair enzyme. a series of d4 muta ...201020861259
[decision of the technical committee virus disinfection of the german association against virus diseases association (dvv) of 1 september 2010 on the exchange of vaccinia virus strain elstree against the modified vaccinia ankara (mva) virus as a test under the virus testing act according to the dvv / rki guideline as amended on 01.08.2008.]. 201020936456
roles of vaccinia virus genes e3l and k3l and host genes pkr and rnase l during intratracheal infection of c57bl/6 mice.the importance of the 2'-5' oligoadenylate synthetase (oas)/rnase l and double-stranded rna (dsrna)-dependent protein kinase (pkr) pathways in host interferon induction resulting from virus infection in response to dsrna has been well documented. in poxvirus infections, the interactions between the vaccinia virus (vv) genes e3l and k3l, which target rnase l and pkr, respectively, serve to prevent the induction of the dsrna-dependent induced interferon response in cell culture. to determine the i ...201020943971
self-cleaving purification tags re-engineered for rapid topo® cloning.in this work, our previously reported δi-cm and δi(g)-cm mutant inteins were rationally re-engineered to be compatible with invitrogen's topo® cloning system. the resulting new inteins include the vaccinia virus topoisomerase i dna recognition sequence tcctt at their 3' ends, making them compatible with the highly convenient one-step topo® cloning method. addition of the topo® recognition sequence resulted in an altered amino acid sequence at the c-termini of the inteins, changing their final fi ...201020945478
phase i safety and immunogenicity evaluation of mva-cmdr, a multigenic, recombinant modified vaccinia ankara-hiv-1 vaccine candidate.we conducted a phase i randomized, dose-escalation, route-comparison trial of mva-cmdr, a candidate hiv-1 vaccine based on a recombinant modified vaccinia ankara viral vector expressing hiv-1 genes env/gag/pol. the hiv sequences were derived from circulating recombinant form crf01_ae, which predominates in thailand. the objective was to evaluate safety and immunogenicity of mva-cmdr in human volunteers in the us and thailand.201021085591
domain swapping reveals complement control protein modules critical for imparting cofactor and decay-accelerating activities in vaccinia virus complement control protein.vaccinia virus encodes a structural and functional homolog of human complement regulators named vaccinia virus complement control protein (vcp). this four-complement control protein domain containing secretory protein is known to inhibit complement activation by supporting the factor i-mediated inactivation of complement proteins, proteolytically cleaved form of c3 (c3b) and proteolytically cleaved form of c4 (c4b) (termed cofactor activity), and by accelerating the irreversible decay of the cla ...201020956343
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