Publications
| Title | Abstract | Year(sorted descending) Filter | PMID Filter |
|---|
| differential diagnosis of orf viruses by a single-step pcr. | the complete nucleotide sequence of the a32l gene (named after vaccinia virus, corresponding with open reading frame 108 of the orf virus and encoding an atpase) of the orf virus was studied using samples of orf virus from infected goats, which were collected from six outbreaks in central taiwan. dna sequence analysis of the a32l genes of these and isolates from other countries showed sequence heterogeneity (base pair variation and deletion) in the 3'-terminal regions. this finding led to the de ... | 2009 | 19409929 |
| the adaptor molecule myd88 directly promotes cd8 t cell responses to vaccinia virus. | vaccinia virus (vacv) elicits a robust cd8 t cell response that plays an important role in host resistance. to date, there is little information on the molecules that are essential to generate large pools of vacv-specific effector cd8 t cells. in this study, we show that the adaptor molecule myd88 is critical for the magnitude of primary cd8 t cell responses to both dominant and subdominant vacv epitopes. myd88(-/-) mice exhibit profound reduction in cd8 t cell expansion and antiviral cytokine p ... | 2009 | 19414781 |
| expanding the repertoire of modified vaccinia ankara-based vaccine vectors via genetic complementation strategies. | modified vaccinia virus ankara (mva) is a safe, highly attenuated orthopoxvirus that is being developed as a recombinant vaccine vector for immunization against a number of infectious diseases and cancers. however, the expression by mva vectors of large numbers of poxvirus antigens, which display immunodominance over vectored antigens-of-interest for the priming of t cell responses, and the induction of vector-neutralizing antibodies, which curtail the efficacy of subsequent booster immunization ... | 2009 | 19421328 |
| selection of appropriate serological tests to measure the incidence of natural leishmania infantum infection during dna/mva prime/boost canine vaccine trials. | in response to the increasing need for field trials of experimental dna vaccines against zoonotic visceral leishmaniasis in dogs, our aim was to validate the use of elisa protocols which will be suitable for detection of natural infection in vaccinated dogs. we have previously demonstrated that dna/modified vaccinia virus ankara (mva) vaccine expressing tryparedoxin peroxidase (tryp) induced high titres of tryp antigen-specific igg in immunized dogs. here we report our findings that seroconversi ... | 2009 | 19386420 |
| hiv escape from natural killer cytotoxicity: nef inhibits nkp44l expression on cd4+ t cells. | hiv infection induces a progressive depletion of cd4 t cells. we showed that nkp44l, a cellular ligand for an activating natural killer (nk) receptor, is expressed on cd4 t cells during hiv infection and is correlated with both cd4 cell depletion and increase in viral load. nkp44lcd4 t cells are highly sensitive to the nk lysis activity. in contrast, hiv-infected cd4 t cells are resistant to nk killing, suggesting that hiv-1 developed strategies to avoid detection by the host cell immunity. | 2009 | 19424050 |
| unwinding by local strand separation is critical for the function of dead-box proteins as rna chaperones. | the dead-box proteins cyt-19 in neurospora crassa and mss116p in saccharomyces cerevisiae are broadly acting rna chaperones that function in mitochondria to stimulate group i and group ii intron splicing and to activate mrna translation. previous studies showed that the s. cerevisiae cytosolic/nuclear dead-box protein ded1p could stimulate group ii intron splicing in vitro. here, we show that ded1p complements mitochondrial translation and group i and group ii intron splicing defects in mss116de ... | 2009 | 19393667 |
| of mice and humans: how good are hla transgenic mice as a model of human immune responses? | previous studies have defined vaccinia virus (vacv)-derived t cell epitopes in vacv-infected human leukocyte antigen-a*0201 (hla-a2.1) transgenic (tg) mice and a2.1-positive human dryvax vaccinees. a total of 14 epitopes were detected in humans and 16 epitopes in a2.1 tg mice; however, only two epitopes were independently reported in both systems. this limited overlap raised questions about the suitability of using hla tg mice as a model system to map human t cell responses to a complex viral pa ... | 2009 | 19534819 |
| vaccinia virus cd8+ t-cell dominance hierarchies cannot be altered by prior immunization with individual peptides. | heterologous prime-boost is a common vaccination strategy to elicit cd8(+) t cells (t(cd8+)), and vaccinia virus (vacv) has been widely used as a boosting vector. studies with other viruses have suggested that priming may reduce responses to native epitopes in boosting vectors as well as improve responses to primed epitopes. we explored this possibility with a vacv model in mice and find that irrespective of an epitope's dominance, prior priming was able to double t(cd8+) responses. more surpris ... | 2009 | 19535449 |
| vaccinia virus g8r protein: a structural ortholog of proliferating cell nuclear antigen (pcna). | eukaryotic dna replication involves the synthesis of both a dna leading and lagging strand, the latter requiring several additional proteins including flap endonuclease (fen-1) and proliferating cell nuclear antigen (pcna) in order to remove rna primers used in the synthesis of okazaki fragments. poxviruses are complex viruses (dsdna genomes) that infect eukaryotes, but surprisingly little is known about the process of dna replication. given our previous results that the vaccinia virus (vacv) g5 ... | 2009 | 19421403 |
| use of b7 costimulatory molecules as adjuvants in a prime-boost vaccination against visna/maedi ovine lentivirus. | rna transcripts of the b7 family molecule (cd80) are diminished in blood leukocytes from animals clinically affected with visna/maedi virus (vmv) infection. this work investigates whether the use of b7 genes enhances immune responses and protection in immunization-challenge approaches. sheep were primed by particle-mediated epidermal bombardment with vmv gag and env gene recombinant plasmids together with plasmids encoding both cd80 and cd86 or cd80 alone, boosted with gag and env gene recombina ... | 2009 | 19538997 |
| inhibition of vaccinia virus replication by peptide aptamers. | a20 protein is a major component of the vaccinia virus replication complex. it binds to the dna polymerase e9, the uracil dna glycosylase d4 and the primase/helicase d5, three proteins that are essential for viral dna synthesis. the identification of molecules able to interact with the replication complex and inhibit its activity is a promising strategy for the design of new anti-orthopoxvirus drugs. in this study, we used a yeast genetic approach to select, from combinatorial libraries, 8-mers ... | 2009 | 19428604 |
| role of cell signaling in poxvirus-mediated foreign gene expression in mammalian cells. | poxviruses have been extensively used as a promising vehicle to efficiently deliver a variety of antigens in mammalian hosts to induce immune responses against infectious diseases and cancer. using recombinant vaccinia virus (vv) and canarypox virus (alvac) expressing enhanced green fluorescent protein (egfp) or multiple hiv-1 gene products, we studied the role of four cellular signaling pathways, the phosphoinositide-3-oh kinase (pi3k), extracellular signal-regulated kinase (erk), p38 mitogen-a ... | 2009 | 19428911 |
| polymerase translocation with respect to single-stranded nucleic acid: looping or wrapping of primer around a poly(a) polymerase. | vaccinia virus protein vp55 translocates continuously with respect to single-stranded nucleic acid while extending its 3'end. here, all key sites of polymerase-primer interaction were identified, demonstrating the wrapping or looping of polyadenylation primer around the polymerase during translocation. side-chain substitutions at one of the sites indicated its requirement for tail extension beyond approximately 12 nucleotides in length, and conformational changes observed upon oligonucleotide bi ... | 2009 | 19446524 |
| early viral protein synthesis is necessary for nf-kappab activation in modified vaccinia ankara (mva)-infected 293 t fibroblast cells. | modified vaccinia ankara (mva) is an attenuated vaccinia virus, and is a promising vaccine vector for variola and monkeypox viruses, as well as for other pathogens. the mva determinants important for vaccine efficacy and immunogenicity are poorly defined. mva infection of fibroblast cells activates nf-kappab, a characteristic not ascribed to wild-type vaccinia viruses. thus, nf-kappab activation, and the subsequent upregulation of host immune molecules, could be one of the determinants for mva's ... | 2009 | 19539971 |
| cell lines from the egyptian fruit bat are permissive for modified vaccinia ankara. | bats are reservoir hosts for a spectrum of infectious diseases. some pathogens (such as hendra, nipah and marburg viruses) appear to use mainly fruit bats as reservoir. we describe designed immortalization of primary fetal cells from the egyptian fruit bat (rousettus aegyptiacus) to facilitate isolation and characterization of pathogens associated with these mammals. three cell lines with different properties were recovered and successful immortalization was confirmed by continuous cultivation f ... | 2009 | 19540275 |
| in vitro host range, multiplication and virion forms of recombinant viruses obtained from co-infection in vitro with a vaccinia-vectored influenza vaccine and a naturally occurring cowpox virus isolate. | poxvirus-vectored vaccines against infectious diseases and cancer are currently under development. we hypothesized that the extensive use of poxvirus-vectored vaccine in future might result in co-infection and recombination between the vaccine virus and naturally occurring poxviruses, resulting in hybrid viruses with unpredictable characteristics. previously, we confirmed that co-infecting in vitro a modified vaccinia virus ankara (mva) strain engineered to express influenza virus haemagglutinin ... | 2009 | 19435511 |
| harnessing the unique local immunostimulatory properties of modified vaccinia ankara (mva) virus to generate superior tumor-specific immune responses and antitumor activity in a diversified prime and boost vaccine regimen. | recombinant poxviruses expressing tumor-associated antigens (taas) are currently being evaluated in clinical trials as an approach to treat various cancers. we have previously generated poxviral vectors expressing a taa and a triad of costimulatory molecules (b7-1, icam-1, and lfa-3; tricom) as transgenes, including replication competent recombinant vaccinia (rv) or replication-defective modified vaccinia ankara (mva), to prime tumor-specific immune responses, and a replication-defective recombi ... | 2009 | 19450631 |
| effective expression of recombinant cytotoxic protein via its attachment to a polyglutamine domain. | inadvertent cytotoxicity may hinder the expression of many recombinant proteins that are of industrial or medicinal importance. here, we show that covalent binding of the influenza a cytotoxic protein m2 to a polyglutamine domain (polyq-m2; qm2) results in significant delay of its cytotoxic effects when compared to wild-type protein (m2wt). we also show that while expression of recombinant m2wt from a/wsn/1933 strain could not be attained in vaccinia virus (vv), polyq-m2 was successfully express ... | 2009 | 19441878 |
| cellular factor yy1 downregulates the human papillomavirus 16 e6/e7 promoter, p97, in vivo and in vitro from a negative element overlapping the transcription-initiation site. | cellular factors that bind to cis sequences in the human papillomavirus 16 (hpv-16) upstream regulatory region (urr) positively and negatively regulate the viral e6 and e7 oncogene promoter, p97. dnase i footprinting has revealed the binding of cellular proteins to two previously undetected cis elements overlapping and 3' of the transcription-initiation site of the p97 promoter. mutations within homologous motifs found in both of these cis elements abolished their negative function in vivo and t ... | 2009 | 19553391 |
| in silico-accelerated identification of conserved and immunogenic variola/vaccinia t-cell epitopes. | epitopes shared by the vaccinia and variola viruses underlie the protective effect of vaccinia immunization against variola infection. we set out to identify a subset of cross-reactive epitopes using bioinformatics and immunological methods. putative t-cell epitopes were computationally predicted from highly conserved open reading frames from seven complete vaccinia and variola genomes using epimatrix. over 100 epitopes bearing low human sequence homology were selected and assessed in hla bindin ... | 2009 | 19559119 |
| proteomic screening of variola virus reveals a unique nf-kappab inhibitor that is highly conserved among pathogenic orthopoxviruses. | identification of the binary interactions between viral and host proteins has become a valuable tool for investigating viral tropism and pathogenesis. here, we present the first systematic protein interaction screening of the unique variola virus proteome by using yeast 2-hybrid screening against a variety of human cdna libraries. several protein-protein interactions were identified, including an interaction between variola g1r, an ankryin/f-box containing protein, and human nuclear factor kappa ... | 2009 | 19451633 |
| the proteoglycan bamacan is a host cellular ligand of vaccinia virus neurovirulence factor n1l. | neurovirulence is one of the pathological complications associated with vaccinia virus (vv) infection/vaccination. although the viral n1l protein has been identified as the neurovirulence factor, none of the host n1l-interacting factors have been identified so far. in the present study, we identified n1l-interacting proteins by screening a human brain cdna expression library with n1l as a bait protein in a yeast two-hybrid analysis. the analysis revealed that n1l interacts with human brain-origi ... | 2009 | 19444697 |
| hypercostimulation through 4-1bb distorts homeostasis of immune cells. | the deleterious side effects associated with a recent clinical trial with anti-cd28 superagonist abs have questioned the use of reagents to costimulatory molecules in human therapy. we now show that sustained signaling from an agonist ab to 4-1bb, a member of the tnfr superfamily, results in detrimental effects on immune cell homeostasis. repeated anti-4-1bb treatment during the reconstitution of hematopoietic cells in irradiated mice engrafted with bone marrow, or in mice infected with vaccinia ... | 2009 | 19454670 |
| vaccinia virus vaccines: past, present and future. | vaccinia virus (vacv) has been used more extensively for human immunization than any other vaccine. for almost two centuries, vacv was employed to provide cross-protection against variola virus, the causative agent of smallpox, until the disease was eradicated in the late 1970s. since that time, continued research on vacv has produced a number of modified vaccines with improved safety profiles. attenuation has been achieved through several strategies, including sequential passage in an alternati ... | 2009 | 19563829 |
| strong ability of nef-specific cd4+ cytotoxic t cells to suppress human immunodeficiency virus type 1 (hiv-1) replication in hiv-1-infected cd4+ t cells and macrophages. | a restricted number of studies have shown that human immunodeficiency virus type 1 (hiv-1)-specific cytotoxic cd4+ t cells are present in hiv-1-infected individuals. however, the roles of this type of cd4+ t cell in the immune responses against an hiv-1 infection remain unclear. in this study, we identified novel nef epitope-specific hla-drb1*0803-restricted cytotoxic cd4+ t cells. the cd4+ t-cell clones specific for nef187-203 showed strong gamma interferon production after having been stimulat ... | 2009 | 19457989 |
| inhibition of nk cell activity by il-17 allows vaccinia virus to induce severe skin lesions in a mouse model of eczema vaccinatum. | threats of bioterrorism have renewed efforts to better understand poxvirus pathogenesis and to develop a safer vaccine against smallpox. individuals with atopic dermatitis are excluded from smallpox vaccination because of their propensity to develop eczema vaccinatum, a disseminated vaccinia virus (vacv) infection. to study the underlying mechanism of the vulnerability of atopic dermatitis patients to vacv infection, we developed a mouse model of eczema vaccinatum. virus infection of eczematous ... | 2009 | 19468065 |
| imaging a genetically engineered oncolytic vaccinia virus (glv-1h99) using a human norepinephrine transporter reporter gene. | oncolytic viral therapy continues to be investigated for the treatment of cancer, and future studies in patients would benefit greatly from a noninvasive modality for assessing virus dissemination, targeting, and persistence. the purpose of this study was to determine if a genetically modified vaccinia virus, glv-1h99, containing a human norepinephrine transporter (hnet) reporter gene, could be sequentially monitored by [(123)i]metaiodobenzylguanidine (mibg) gamma-camera and [(124)i]mibg positro ... | 2009 | 19470726 |
| assembly and disassembly of the capsid-like external scaffold of immature virions during vaccinia virus morphogenesis. | infectious poxvirus particles are unusual in that they are brick shaped and lack symmetry. nevertheless, an external honeycomb lattice comprised of a capsid-like protein dictates the spherical shape and size of immature poxvirus particles. in the case of vaccinia virus, trimers of 63-kda d13 polypeptides form the building blocks of the lattice. in the present study, we addressed two questions: how d13, which has no transmembrane domain, associates with the immature virion (iv) membrane to form t ... | 2009 | 19570860 |
| cowpox virus expresses a novel ankyrin repeat nf-kappab inhibitor that controls inflammatory cell influx into virus-infected tissues and is critical for virus pathogenesis. | many pathogenic orthopoxviruses like variola virus, monkeypox virus, and cowpox virus (cpxv), but not vaccinia virus, encode a unique family of ankyrin (ank) repeat-containing proteins that interact directly with nf-kappab1/p105 and inhibit the nf-kappab signaling pathway. here, we present the in vitro and in vivo characterization of the targeted gene knockout of this novel nf-kappab inhibitor in cpxv. our results demonstrate that the vcpx-006ko uniquely induces a variety of nf-kappab-controlled ... | 2009 | 19570875 |
| treatment with cyclooxygenase-2 inhibitors enables repeated administration of vaccinia virus for control of ovarian cancer. | metastatic ovarian cancer is the leading cause of death among women with gynecologic malignancies in the united states. the lack of effective treatment for patients with advanced ovarian cancer warrants development of innovative therapies. cancer therapy using oncolytic viruses represents a promising new approach for controlling tumors. vaccinia virus has been shown to preferentially infect tumor cells but not normal tissue. however, oncolytic therapy using recombinant viruses faces the limitati ... | 2009 | 19471247 |
| progressive vaccinia in a military smallpox vaccinee - united states, 2009. | progressive vaccinia (pv), previously known as vaccinia necrosum, vaccinia gangrenosum, or disseminated vaccinia, is a rare, often fatal adverse event after vaccination with smallpox vaccine, which is made from live vaccinia virus. during recent vaccination programs potential cases of pv were investigated, but none met standard case definitions. pv has not been confirmed to have occurred in the united states since 1987. on march 2, 2009, a u.s. navy hospital contacted the poxvirus program at cdc ... | 2009 | 19478722 |
| viral sequestration of antigen subverts cross presentation to cd8(+) t cells. | virus-specific cd8(+) t cells (t(cd8+)) are initially triggered by peptide-mhc class i complexes on the surface of professional antigen presenting cells (papc). peptide-mhc complexes are produced by two spatially distinct pathways during virus infection. endogenous antigens synthesized within virus-infected papc are presented via the direct-presentation pathway. many viruses have developed strategies to subvert direct presentation. when direct presentation is blocked, the cross-presentation path ... | 2009 | 19478869 |
| new avian suspension cell lines provide production of influenza virus and mva in serum-free media: studies on growth, metabolism and virus propagation. | few suspension cells can be used for vaccine manufacturing today as they either do not meet requirements from health regulatory authorities or do not produce high virus titres. two new avian designer cell lines (age1.cr and age1.cr.pix) that have been adapted to grow in suspension in serum-free medium were evaluated for their potential as host cells for influenza and modified vaccinia ankara (mva, wild type) vaccine production. their metabolism was studied during growth in static (t-flasks) and ... | 2009 | 19531390 |
| the double-stranded rna binding domain of the vaccinia virus e3l protein inhibits both rna- and dna-induced activation of interferon beta. | vaccinia virus, a large dna virus that replicates in the cytoplasm, expresses its e3l protein to inhibit the cellular innate immune response and apoptosis. e3l is a bifunctional protein that contains an n-terminal dna binding domain (bd) and a c-terminal double-stranded rna (dsrna)-bd (residues 100-190), both of which contribute to viral pathogenesis by blocking the activation of cellular genes that respond to the viral infection. we report that expression of the dsrna-bd alone inhibits not only ... | 2009 | 19584049 |
| comparative sequence analysis of a-type inclusion (ati) and p4c proteins of orthopoxviruses that produce typical and atypical ati phenotypes. | some orthopoxviruses produce large proteinaceous intracellular bodies, known as a-type inclusions (atis) during infection of host cells. virions associate with atis resulting in distinct phenotypes referred to as v+, v+/ and v⁻. the phenotype v+ has the virions embedded in the ati matrix; v⁻ has no virions embedded within or on the surface of the ati matrix, whereas an aberrant phenotype, the v+/ has virions only on the surface of atis. viruses that do not produce ati are designated as v⁰. recom ... | 2009 | 19533319 |
| statistical approach to estimate vaccinia-specific neutralizing antibody titers using a high-throughput assay. | because of the bioterrorism threat posed by agents such as variola virus, considerable time, resources, and effort have been devoted to biodefense preparation. one avenue of this research has been the development of rapid, sensitive, high-throughput assays to validate immune responses to poxviruses. here we describe the adaptation of a beta-galactosidase reporter-based vaccinia virus neutralization assay to large-scale use in a study that included over 1,000 subjects. we also describe the statis ... | 2009 | 19535540 |
| vaccinia virus infection & temporal analysis of virus gene expression: part 1. | the family poxviridae consists of large double-stranded dna containing viruses that replicate exclusively in the cytoplasm of infected cells. members of the orthopox genus include variola, the causative agent of human small pox, monkeypox, and vaccinia (vac), the prototypic member of the virus family. within the relatively large (approximately 200 kb) vaccinia genome, three classes of genes are encoded: early, intermediate, and late. while all three classes are transcribed by virally-encoded rna ... | 2009 | 19488021 |
| adenoviral and aav-mediated gene transfer to the inner ear: role of serotype, promoter, and viral load on in vivo and in vitro infection efficiencies. | the lack of effective treatments for many forms of hearing and vestibular disorders has produced interest in virally mediated gene therapies. however, to develop a gene therapy strategy that would successfully treat inner ear disorders, appropriate viral vectors capable of transfecting cochlear and support cells must be identified. while virally mediated gene transfer into the inner ear has been accomplished using herpes simplex type i virus, vaccinia virus, retroviruses, adenovirus, and adeno-a ... | 2009 | 19494574 |
| orfeome approach to the clonal, hla allele-specific cd4 t-cell response to a complex pathogen in humans. | the cd4 t-cell response to vaccinia promotes antibody and long-term cd8 responses. hla class ii molecules present microbial epitopes to cd4 t-cells. in humans, at least 3 loci encode cell-surface peptide-binding hla class ii heterodimers. using intracellular cytokine cytometry (icc) assays, we determined that hla dr had the strongest contribution to vaccinia antigen presentation. among panels of vaccinia-restricted t-cell clones, most were dr-restricted but rare dq-restricted clones were also re ... | 2009 | 19520082 |
| pulmonary eosinophilia is attenuated by early responding cd8(+) memory t cells in a murine model of rsv vaccine-enhanced disease. | vaccination with formalin-inactivated respiratory syncytial virus (rsv) vaccine results in enhanced respiratory tract inflammation and injury following subsequent rsv infection. rsv vaccine-enhanced disease can also be produced in mice by prior vaccination with a vaccinia virus vector containing the rsv g protein, followed by intranasal infectious rsv challenge, a process characterized by induction of a potent memory cd4(+) t-cell response to challenge infection with some features characteristic ... | 2009 | 19594395 |
| the immunology of smallpox vaccines. | in spite of the eradication of smallpox over 30 years ago; orthopox viruses such as smallpox and monkeypox remain serious public health threats both through the possibility of bioterrorism and the intentional release of smallpox and through natural outbreaks of emerging infectious diseases such as monkeypox. the eradication effort was largely made possible by the availability of an effective vaccine based on the immunologically cross-protective vaccinia virus. although the concept of vaccination ... | 2009 | 19524427 |
| phosphorylation-driven assembly of the rip1-rip3 complex regulates programmed necrosis and virus-induced inflammation. | programmed necrosis is a form of caspase-independent cell death whose molecular regulation is poorly understood. the kinase rip1 is crucial for programmed necrosis, but also mediates activation of the prosurvival transcription factor nf-kappab. we postulated that additional molecules are required to specifically activate programmed necrosis. using a rna interference screen, we identified the kinase rip3 as a crucial activator for programmed necrosis induced by tnf and during virus infection. rip ... | 2009 | 19524513 |
| diverse recognition of conserved orthopoxvirus cd8+ t cell epitopes in vaccinated rhesus macaques. | vaccinia virus (vacv) induces a vigorous virus-specific cd8+ t cell response that plays an important role in control of poxvirus infection. to identify immunodominant poxvirus proteins and to facilitate future testing of smallpox vaccines in non-human primates, we used an algorithm for the prediction of vacv peptides able to bind to the common macaque mhc class i molecule mamu-a*01. we synthesized 294 peptides derived from 97 vacv orfs; 100 of these peptides did not contain the canonical proline ... | 2009 | 19531389 |
| modified vaccinia ankara strains with identical coding sequences actually represent complex mixtures of viruses that determine the biological properties of each strain. | modified vaccinia ankara (mva) was developed by serial passages on chicken embryo fibroblast cells. after passage 570, the virus was considered homogenous and genetically stable. three mva strains (mva-572, mva-i721 and mva-bn) have been analyzed and shown to be 100% genetically identical; although significant differences in their phenotypes were illustrated. all mva strains except mva-bn replicated in human cells, or killed immune suppressed mice. viruses isolated from dead animals were shown t ... | 2009 | 19539582 |
| mtor regulates memory cd8 t-cell differentiation. | memory cd8 t cells are a critical component of protective immunity, and inducing effective memory t-cell responses is a major goal of vaccines against chronic infections and tumours. considerable effort has gone into designing vaccine regimens that will increase the magnitude of the memory response, but there has been minimal emphasis on developing strategies to improve the functional qualities of memory t cells. here we show that mtor (mammalian target of rapamycin, also known as frap1) is a ma ... | 2009 | 19543266 |
| innate immune sensing of modified vaccinia virus ankara (mva) is mediated by tlr2-tlr6, mda-5 and the nalp3 inflammasome. | modified vaccinia virus ankara (mva) is an attenuated double-stranded dna poxvirus currently developed as a vaccine vector against hiv/aids. profiling of the innate immune responses induced by mva is essential for the design of vaccine vectors and for anticipating potential adverse interactions between naturally acquired and vaccine-induced immune responses. here we report on innate immune sensing of mva and cytokine responses in human thp-1 cells, primary human macrophages and mouse bone marrow ... | 2009 | 19543380 |
| recombinant in vitro assembled hepatitis c virus core particles induce strong specific immunity enhanced by formulation with an oil-based adjuvant. | in the present work, immunogenicity of recombinant in vitro assembled hepatitis c virus core particles, hccag.120-vlps, either alone or in combination with different adjuvants was evaluated in balb/c mice. hccag.120-vlps induced high titers of anti-hccag.120 antibodies and virus-specific cellular immune responses. particularly, hccag.120-vlps induced specific delayed type hypersensitivity, and generated a predominant t helper 1 cytokine pro file in immunized mice. in addition, hccag.120-vlps pri ... | 2009 | 19621132 |
| spread of cantagalo virus to northern brazil. | 2009 | 19624947 | |
| the initial phase of an immune response functions to activate regulatory t cells. | an early reaction of cd4(+) t lymphocytes to ag is the production of cytokines, notably il-2. to detect cytokine-dependent responses, naive ag-specific t cells were stimulated in vivo and the presence of phosphorylated stat5 molecules was used to identify the cell populations responding to il-2. within hours of t cell priming, il-2-dependent stat5 phosphorylation occurred primarily in foxp3(+) regulatory t cells. in contrast, the ag-specific t cells received stat5 signals only after repeated ag ... | 2009 | 19542444 |
| effector t-cell differentiation during viral and bacterial infections: role of direct il-12 signals for cell fate decision of cd8(+) t cells. | to study the role of il-12 as a third signal for t-cell activation and differentiation in vivo, direct il-12 signaling to cd8(+) t cells was analyzed in bacterial and viral infections using the p14 t-cell adoptive transfer model with cd8(+) t cells that lack the il-12 receptor. results indicate that cd8(+) t cells deficient in il-12 signaling were impaired in clonal expansion after listeria monocytogenes infection but not after infection with lymphocytic choriomeningitis virus, vaccinia virus or ... | 2009 | 19548244 |
| vaccinia virus h7 protein contributes to the formation of crescent membrane precursors of immature virions. | crescent membranes are the first viral structures that can be discerned during poxvirus morphogenesis. the crescents consist of a lipoprotein membrane and an outer lattice scaffold, which provides uniform curvature. relatively little is known regarding the composition of the crescent membrane or its mode of formation. here, we show that the h7 protein, which is conserved in all vertebrate poxviruses but has no discernible functional motifs or nonpoxvirus homologs, contributes to the formation of ... | 2009 | 19553304 |
| immunogenicity and protective efficacy of semliki forest virus replicon-based dna vaccines encoding goatpox virus structural proteins. | goatpox, caused by goatpox virus (gtpv), is an acute feverish and contagious disease in goats often associated with high morbidity and high mortality. to resolve potential safety risks and vaccination side effects of existing live attenuated goatpox vaccine (av41), two semliki forest virus (sfv) replicon-based bicistronic expression dna vaccines (pcsm-aal and pcsm-baa) which encode gtpv structural proteins corresponding to the vaccinia virus proteins a27, l1, a33, and b5, respectively, were cons ... | 2009 | 19559453 |
| disinfection efficacy against parvoviruses compared with reference viruses. | some virus species can resist harsh environmental conditions, surviving on surfaces for long periods with the possibility of being transmitted to susceptible hosts. studies are limited on the efficacy of disinfectants against viruses dried onto surfaces, in particular, with the identification of new pathogenic non-enveloped viruses that are expected to have high resistance to disinfection, such as parvoviruses. in this study a range of commonly used biocides, including heat, was tested against p ... | 2009 | 19646784 |
| selective removal of stratum corneum by microdermabrasion to increase skin permeability. | this study sought to determine if microdermabrasion can selectively remove stratum corneum to increase skin permeability. although, microdermabrasion has been used for cosmetic treatment of skin for decades, no study has assessed the detailed effects of microdermabrasion conditions on the degree of skin tissue removal. therefore, we histologically characterized the skin of rhesus macaques and human volunteers after microdermabrasion at different conditions. using mobile tip microdermabrasion, an ... | 2009 | 19559791 |
| vaccination of renal cell cancer patients with modified vaccinia ankara delivering the tumor antigen 5t4 (trovax) alone or administered in combination with interferon-alpha (ifn-alpha): a phase 2 trial. | attenuated vaccinia virus, modified vaccinia ankara (mva) has been engineered to deliver the tumor antigen 5t4 (trovax). mva-5t4 has been evaluated in an open-label phase 2 trial in metastatic renal cell cancer patients in which the vaccine was administered alone or in combination with interferon-alpha-2b (ifn-alpha). the safety, immunologic, and clinical efficacy of mva-5t4 with or without ifn-alpha was determined. twenty-eight patients with metastatic renal cell cancer were treated with mva-5t ... | 2009 | 19561532 |
| gene therapy for antitumor vaccination. | tumor immunotherapy depends on the interactions between the host, the tumor, and the immune system. recent data suggests that priming of antigen-specific t cells alone may not be adequate for mediating regression of established tumors because of the immune inhibitory influences within the tumor microenvironment. thus, we developed a recombinant vaccinia virus vector to express single or multiple t cell costimulatory molecules as a vector for local gene therapy in patients with malignant melanoma ... | 2009 | 19565920 |
| activation of mda5 requires higher-order rna structures generated during virus infection. | recognition of virus presence via rig-i (retinoic acid inducible gene i) and/or mda5 (melanoma differentiation-associated protein 5) initiates a signaling cascade that culminates in transcription of innate response genes such as those encoding the alpha/beta interferon (ifn-alpha/beta) cytokines. it is generally assumed that mda5 is activated by long molecules of double-stranded rna (dsrna) produced by annealing of complementary rnas generated during viral infection. here, we used an antibody to ... | 2009 | 19656871 |
| design and testing of novel oncolytic vaccinia strains. | oncolytic or replication-selective viruses have been used as powerful tools for the delivery of therapeutic genes to tumors. because these vectors are capable of replicating within the tumor, the therapeutic gene is amplified within the target tissue itself, resulting in the spread of the virus both within the tumor, and sometimes also between tumors. vaccinia virus holds many advantages when serving as the backbone for oncolytic viral strains, including a large cloning capacity (at least 25 kbp ... | 2009 | 19565925 |
| growth characteristic of camel pox and vaccinia viruses in embryonated eggs and cell culture. | camel pox viruses isolated in sudan and vd45 (african camel pox strain) and vaccinia virus (elstree strain) were used for inoculation of chorioallantoic membrane (cam) of embryonated eggs (ee) and cell culture (cc). in ee lesions were seen as pocks ranging in size from 1 to 1.5 mm in diameter, and they increase in size with serial passage and taking opaque- white and opaque- yellow colors. when propagated in vero cells, these viruses gave clear cpe, characterized by rounding of cells, plaque for ... | 2009 | 18626782 |
| overexpression of il-1alpha in skin differentially modulates the immune response to scarification with vaccinia virus. | transepidermal inoculation of vaccinia virus (vv), or scarification, has been used effectively for the induction of specific and long-lasting immunity to smallpox and is superior to other routes of immunization. scarification of individuals with atopic skin disease or immune deficiency, however, can lead to persistent viral replication and result in significant morbidity and mortality. these effects of scarification presumably reflect the unique immunological properties of skin and the immune ce ... | 2009 | 18615110 |
| in vitro activity of cidofovir against the emerging cantagalo virus and the smallpox vaccine strain ioc. | the antiviral effect of cidofovir was evaluated against two strains of vaccinia virus: the field strain cantagalo virus (ctgv) and the smallpox vaccine ioc. the drug severely inhibited virus replication, revealing an ec(50) (drug concentration required to inhibit 50% of virus replication) of 7.68 microm and 9.66 microm, respectively, for ctgv and vaccine strain ioc. similarly, other field isolates of cantagalo-like viruses recently collected in distinct outbreaks were equally sensitive to the dr ... | 2009 | 18804965 |
| structure-activity relationships for dipeptide prodrugs of acyclovir: implications for prodrug design. | a series of water-soluble dipeptide ester prodrugs of the antiviral acyclovir (acv) were evaluated for their chemical stability, cytotoxicity, and antiviral activity against several strains of herpes simplex-1 and -2, vaccinia, vesicular stomatitis, cytomegalovirus and varicella zoster viruses. acv dipeptide esters were very active against herpetic viruses, independently of the rate at which they liberate the parent drug. their minimum cytotoxic concentrations were above 100 microm and the resul ... | 2009 | 18848738 |
| virus inactivation in a factor viii/vwf concentrate treated using a solvent/detergent procedure based on polysorbate 20. | treatment with solvent/detergent is a widely used method for ensuring the virus safety of plasma products. in the present study, virus inactivation by a novel solvent/detergent combination, i.e. tnbp (tri-n-butyl phosphate) and polysorbate 20 during the manufacture of the factor viii/vwf concentrate optivate has been investigated. the inactivation of most enveloped viruses was rapid, i.e. > 5 log in 2 min, although the inactivation of vaccinia virus was slower, i.e. 4 log in 1h. virus inactivati ... | 2009 | 18848782 |
| pharmacodynamics of cidofovir for vaccinia virus infection in an in vitro hollow-fiber infection model system. | variola major virus remains a potent weapon of bioterror. there is currently an investigational-new-drug application for cidofovir for the therapy of variola major virus infections. stittelaar and colleagues compared the levels of effectiveness of postexposure smallpox vaccination (elstree-rivm) and antiviral treatment with cidofovir or an acyclic nucleoside phosphonate analogue 6-[2-(phosphonomethoxy)alkoxy]-2,4-diaminopyrimidine (hpmpo-dapy) after lethal intratracheal infection of cynomolgus m ... | 2009 | 18852271 |
| the addition of tumor necrosis factor plus beta interferon induces a novel synergistic antiviral state against poxviruses in primary human fibroblasts. | tumor necrosis factor (tnf) and members of the interferon (ifn) family have been shown to independently inhibit the replication of a variety of viruses. in addition, previous reports have shown that treatment with various combinations of these antiviral cytokines induces a synergistic antiviral state that can be significantly more potent than addition of any of these cytokines alone. the mechanism of this cytokine synergy and its effects on global gene expression, however, are not well character ... | 2009 | 18971273 |
| systemic dna immunization against ovine lentivirus using particle-mediated epidermal delivery and modified vaccinia ankara encoding the gag and/or env genes. | to determine whether systemic immunization with plasmid dna and virus vector against visna/maedi virus (vmv) would induce protective immune responses, sheep were immunized with vmv gag and/or env sequences using particle-mediated epidermal bombardment and injection of recombinant modified vaccinia ankara. the results showed that immunization induced both humoral and cell-mediated responses prior to and after virus challenge. the vaccination protocol did not prevent infection, but immunization wi ... | 2009 | 18984025 |
| smallpox revaccination of 21000 first responders in israel: lessons learned. | between july 2002 and april 2003, over 21000 individuals were revaccinated against smallpox by the israeli ministry of health. the objectives of the campaign were to create an immunized core of first responders, to review vaccination techniques, and to produce vaccinia immune globulin (vig). | 2009 | 19010077 |
| effect of therapeutic immunization using ad5/35 and mva vectors on siv infection of rhesus monkeys undergoing antiretroviral therapy. | antiretroviral therapy (art) effectively slows the progression of aids. however, drug resistance and/or toxicity can limit the utility of art in many patients. in this study, we assessed whether a viral vector-based vaccine can be used as a therapeutic vaccine in simian immunodeficiency virus (siv)-infected monkeys. the effect of vaccinating sivmac239-infected rhesus monkeys with an siv gag and gp120-expressing adenovirus (ad) vector vaccine and a modified vaccinia ankara (mva) vaccine was explo ... | 2009 | 18923453 |
| postexposure immunization with modified vaccinia virus ankara or conventional lister vaccine provides solid protection in a murine model of human smallpox. | decades after the cessation of smallpox vaccination, the potential of the deliberate release of pathogenic orthopoxviruses has forced a reconsideration of using these extremely efficient human vaccines. scenarios of sudden biothreats have prompted demand for rapidly protective vaccination. however, the feasibility of short-term vaccination (i.e., vaccination shortly before exposure) with vaccinia virus (vacv) is uncertain. | 2009 | 19012492 |
| lentiviral gene transfer to reduce atherosclerosis progression by long-term cc-chemokine inhibition. | cc-chemokines are important mediators in the pathogenesis of atherosclerosis. atherosclerosis progression is reduced by high-level, short-term inhibition of cc-chemokine activity, for example by adenoviral gene transfer. however, atherosclerosis is a chronic condition where short-term effects, while demonstrating proof-of-principle, are unlikely to provide maximum therapeutic benefit. accordingly, we generated a recombinant lentivirus, lenti35k, encoding the broad-spectrum cc chemokine inhibitor ... | 2009 | 18800153 |
| vaccinia virus extracellular enveloped virion neutralization in vitro and protection in vivo depend on complement. | antibody neutralization is an important component of protective immunity against vaccinia virus (vacv). two distinct virion forms, mature virion and enveloped virion (mv and ev, respectively), possess separate functions and nonoverlapping immunological properties. in this study we examined the mechanics of ev neutralization, focusing on ev protein b5 (also called b5r). we show that neutralization of ev is predominantly complement dependent. from a panel of high-affinity anti-b5 monoclonal antibo ... | 2009 | 19019965 |
| poxvirus k7 protein adopts a bcl-2 fold: biochemical mapping of its interactions with human dead box rna helicase ddx3. | poxviruses have evolved numerous strategies to evade host innate immunity. vaccinia virus k7 is a 149-residue protein with previously unknown structure that is highly conserved in the orthopoxvirus family. k7 bears sequence and functional similarities to a52, which interacts with interleukin receptor-associated kinase 2 and tumor necrosis factor receptor-associated factor 6 to suppress nuclear factor kappab activation and to stimulate the secretion of the anti-inflammatory cytokine interleukin-1 ... | 2009 | 18845156 |
| encephalitis after secondary smallpox vaccination. | we describe a case of post-secondary vaccination encephalitis in a smallpox vaccine recipient and discuss detection of intrathecal antibody to vaccinia virus as a potential diagnostic test. | 2009 | 19025490 |
| a critical role for direct tlr2-myd88 signaling in cd8 t-cell clonal expansion and memory formation following vaccinia viral infection. | recent advances have suggested a crucial role of the innate immunity in shaping adaptive immune responses. how activation of innate immunity promotes adaptive t-cell responses to pathogens in vivo is not fully understood. it has been thought that toll-like receptor (tlr)-mediated control of adaptive t-cell responses is mainly achieved by the engagement of tlrs on antigen-presenting cells to promote their maturation and function. in this study, we showed that direct tlr2-myeloid differentiating f ... | 2009 | 18948575 |
| eczema vaccinatum resulting from the transmission of vaccinia virus from a smallpox vaccinee: an investigation of potential fomites in the home environment. | on march 3, 2007, a 2-year-old boy was hospitalized with eczema vaccinatum. his two siblings, one with eczema, were subsequently removed from the home. swabs of household items obtained on march 13th were analyzed for orthopoxvirus dna signatures with real-time pcr. virus culture was attempted on positive specimens. eight of 25 household samples were positive by pcr for orthopoxvirus; of these, three yielded viable vaccinia virus in culture. both siblings were found to have serologic evidence of ... | 2009 | 19027813 |
| chronic lymphocytic leukemia (cll) cells genetically modified to express b7-1, icam-1, and lfa-3 confer apc capacity to t cells from cll patients. | in chronic lymphocytic leukemia (cll), malignant b cells and nonmalignant t cells exhibit dysfunction. we previously demonstrated that infection of cll cells with modified vaccinia ankara (mva) expressing the costimulatory molecules b7-1, icam-1, and lfa-3 (designated tricom) increased expression of these costimulatory molecules on the surface of cll cells and thus augmented their antigen-presenting capability. here, we evaluate the effect of mva-tricom-modified cll cells on t cells. following i ... | 2009 | 19009294 |
| activities of certain 5-substituted 4'-thiopyrimidine nucleosides against orthopoxvirus infections. | as part of a program to identify new compounds that have activity against orthopoxviruses, a number of 4'-thionucleosides were synthesized and evaluated for their efficacies against vaccinia and cowpox viruses. seven compounds that were active at about 1 microm against both viruses in human cells but that did not have significant toxicity were identified. the 5-iodo analog, 1-(2-deoxy-4-thio-beta-d-ribofuranosyl)-5-iodouracil (4'-thioidu), was selected as a representative molecule; and this comp ... | 2009 | 19029322 |
| use of an oncolytic vaccinia virus for the treatment of canine breast cancer in nude mice: preclinical development of a therapeutic agent. | mammary cancers together with cancers of the skin account for about 60% of the total cancers occurring in dogs. the veterinary options for therapeutic management of canine mammary cancer are limited and prognosis for such patients is poor. in this study, we analyzed the functionality of the oncolytic vaccinia virus strain glv-1h68 as a possible therapeutic agent for canine mammary cancer. cell culture data demonstrated that glv-1h68 efficiently infected and destroyed cells of the canine mammary ... | 2009 | 18949014 |
| real-time intraoperative detection of melanoma lymph node metastases using recombinant vaccinia virus glv-1h68 in an immunocompetent animal model. | there is a clinical need for improved intraoperative detection of lymph node metastases from malignant melanoma (mm). we aimed to investigate the use of recombinant vaccinia virus glv-1h68, expressing green fluorescent protein (gfp), for real-time intraoperative detection of melanoma lymph node metastases in an immunocompetent animal model. mice bearing foot pad tumors received intratumoral injections of glv-1h68, and 48 hr later were evaluated for popliteal lymph node metastasis using noninvasi ... | 2009 | 19035444 |
| response surface methodology to determine optimal cytokine responses in human peripheral blood mononuclear cells after smallpox vaccination. | feasibility, amount of sample aliquots, processing time and cost are critical considerations for optimizing and conducting assays for large-population based studies. well designed statistical approaches that quickly identify optimal conditions for a given assay could assist efficient completion of the laboratory assays for such studies. for example, assessment of the profile of secreted cytokines is important in understanding the immune response after vaccination. to characterize the cytokine im ... | 2009 | 19038260 |
| vaccinia virus proteins activate human dendritic cells to induce t cell responses in vitro. | the mechanisms of protection elicited by smallpox vaccine in humans have not been delineated. dendritic cells (dcs) are the most potent of professional antigen presenting cells which on activation modulate both innate and adaptive immune responses. immunogenic proteins of vaccinia virus have been identified with protein microarray technology. we have investigated the effect of three most immunogenic proteins, d8l, d13l, and h3l on human monocyte-derived dcs with a view to understand the mechanis ... | 2009 | 18977270 |
| effects of a transferring antibody against neospora caninum infection in a murine model. | we investigated the roles of a transferring antibody against neospora caninum infection based on a murine model using recombinant vaccinia virus carrying ncsrs2 gene. higher levels of anti-ncsrs2 antibody were detected in surviving offspring from vaccinated dams than controls while the transferring anti-ncsag1 antibody was detected in the surviving offspring from unvaccinated dams. after mating, the female mice with transferring antibody against n. caninum were challenged with the parasites in m ... | 2009 | 19056179 |
| the effect of nitric oxide on vaccinia virus-encoded ribonucleotide reductase. | growth inhibition of the dna virus vaccinia (vacv) by no is known to occur at the level of dna synthesis. this inhibition is partially reversed by addition of deoxyribonucleosides, suggesting that no or no-related species inhibit viral ribonucleotide reductase (rr). however, the effect of no on vacv-encoded rr or other dna-synthesizing enzymes has not been demonstrated. in order to study the effects of no on vacv-encoded rr, dna polymerase (dna pol) and thymidine kinase (tk), we generated a vacv ... | 2009 | 18951991 |
| bidirectional transcriptional promoters in the vaccinia virus genome. | vaccinia virus intermediate and late class transcriptional promoters each have two essential sequence elements: an initiator at the transcriptional start site and an upstream core element. many of the transcription units in the viral genome are oriented divergently with insufficient nucleotides between the start of the open reading frames to accommodate two separate upstream core elements in their promoters. this raises the possibility that two promoters could share essential elements. reporter ... | 2009 | 19064274 |
| immunogenicity and protective efficacy of prime-boost regimens with recombinant (delta)urec hly+ mycobacterium bovis bcg and modified vaccinia virus ankara expressing m. tuberculosis antigen 85a against murine tuberculosis. | in the light of the recent emergence of multidrug-resistant and extensively drug-resistant strains of mycobacterium tuberculosis, the epidemic of tuberculosis (tb) in populations coinfected with human immunodeficiency virus, and the failure of mycobacterium bovis bacillus calmette-guerin (bcg) to protect against disease, new vaccines against tb are urgently needed. two promising new vaccine candidates are the recombinant deltaurec hly(+) bcg (recbcg), which has been developed to replace the curr ... | 2009 | 19064635 |
| dna binding and cleavage by the fowlpox virus resolvase. | the first steps of poxvirus dna synthesis yield concatemeric arrays of covalently linked genomes. the virus-encoded holliday junction resolvase is required to process concatemers into unit-length genomes for packaging. previous studies of the vaccinia virus resolvase have been problematic due to poor protein solubility. we found that fowlpox virus resolvase was much more tractable. fowlpox resolvase formed complexes with a variety of branched dna substrates, but not linear dna, and had the highe ... | 2009 | 19004818 |
| optimization of human immunodeficiency virus gag expression by newcastle disease virus vectors for the induction of potent immune responses. | one attractive strategy for the development of a human immunodeficiency virus (hiv) vaccine is the use of viral vectors with a proven safety profile and an absence of preexisting immunity in humans, such as newcastle disease virus (ndv). several ndv vaccine vectors have been generated, and their immunogenicities have been investigated with different animal models. however, a systematic study to evaluate the optimal insertion site of the foreign antigens into ndv that results in enhanced immune r ... | 2009 | 19004953 |
| an avian cell line designed for production of highly attenuated viruses. | several viral vaccines, including highly promising vectors such as modified vaccinia ankara (mva), are produced on chicken embryo fibroblasts. dependence on primary cells complicates production especially in large vaccination programs. with primary cells it is also not possible to create packaging lines for replication-deficient vectors that are adapted to proliferation in an avian host. to obviate requirement for primary cells permanent lines from specific tissues of muscovy duck were derived ( ... | 2009 | 19071186 |
| role for ccr5 in dissemination of vaccinia virus in vivo. | in an earlier report, we provided evidence that expression of ccr5 by primary human t cells renders them permissive for vaccinia virus (vacv) replication. this may represent a mechanism for dissemination throughout the lymphatic system. to test this hypothesis, wild-type ccr5(+/+) and ccr5 null mice were challenged with vacv by intranasal inoculation. in time course studies using different infective doses of vacv, we identified viral replication in the lungs of both ccr5(+/+) and ccr5(-/-) mice, ... | 2009 | 19073715 |
| products and substrate/template usage of vaccinia virus dna primase. | vaccinia virus encodes a 90-kda protein conserved in all poxviruses, with dna primase and nucleoside triphosphatase activities. dna primase products, synthesized with a single stranded varphix174 dna template, were resolved as dinucleotides and long rnas on denaturing polyacrylamide and agarose gels. following phosphatase treatment, the dinucleotides gpc and apc in a 4:1 ratio were identified by nearest neighbor analysis in which (32)p was transferred from [alpha-(32)p]ctp to initiating purine n ... | 2009 | 19007959 |
| [human infections caused by vaccinia-like poxviruses in brazil]. | since 1999, human infection caused by orthopoxvirus has been observed in at least eight brazilian states, with the presence of vesicles that evolve to pustules and crusts, especially on the hands, arms and face, after contact with cows showing comparable lesions on the udder. in addition to the skin lesions, there have been descriptions of patients with axillary ganglionic reactions that are sometimes painful, along with fever, headache, fatigue, dehydration, anorexia, sudoresis, arthralgia and ... | 2009 | 20209353 |
| vaccinia virus decreases major histocompatibility complex (mhc) class ii antigen presentation, t-cell priming, and peptide association with mhc class ii. | vaccinia virus (vacv) is the current live virus vaccine used to protect humans against smallpox and monkeypox, but its use is contraindicated in several populations because of its virulence. it is therefore important to elucidate the immune evasion mechanisms of vacv. we found that vacv infection of antigen-presenting cells (apcs) significantly decreased major histocompatibility complex (mhc) ii antigen presentation and decreased synthesis of 13 chemokines and cytokines, suggesting a potent vira ... | 2009 | 20067538 |
| f11-mediated inhibition of rhoa signalling enhances the spread of vaccinia virus in vitro and in vivo in an intranasal mouse model of infection. | the cortical actin cytoskeleton beneath the plasma membrane represents a physical barrier that vaccinia virus has to overcome during its exit from an infected cell. previous observations using overexpression and pharmacological approaches suggest that vaccinia enhances its release by modulating the cortical actin cytoskeleton by inhibiting rhoa signalling using the viral protein f11. we have now examined the role of f11 and its ability to interact with rhoa to inhibit its downstream signalling i ... | 2009 | 20041165 |
| antiviral activity of solanum paniculatum extract and constituents. | solanum species are traditionally employed as antiherpes and anticancer agents in different countries. s. paniculatum has widespread ethnomedical uses in brazil, including the treatment of viral infections. this paper reports on the isolation of neotigogenin (1) and the new compound delta25(27)-tigogenin-3-o-beta-d-glucopyranoside (2), obtained as a mixture of r and s diastereoisomers at c22 from an ethanol extract of s. paniculatum leaves, along with the determination of their cytotoxicity agai ... | 2009 | 20158151 |
| a phase 1 study to evaluate the safety and immunogenicity of a recombinant hiv type 1 subtype c-modified vaccinia ankara virus vaccine candidate in indian volunteers. | a recombinant modified vaccinia ankara virus vaccine candidate (tbc-m4) expressing hiv-1 subtype c env, gag, tat-rev, and nef-rt genes was tested in a randomized, double-blind, dose escalation phase i trial in 32 hiv-uninfected healthy volunteers who received three intramuscular injections of tbc-m4 at 0, 1, and 6 months of 5 x 10(7) plaque-forming units (pfu) (low dosage, ld) (n = 12) or 2.5 x 10(8) pfu (high dosage, hd) (n = 12) or placebo (n = 8). local and systemic reactogenicity was experie ... | 2009 | 19943789 |
| definition of epitopes and antigens recognized by vaccinia specific immune responses: their conservation in variola virus sequences, and use as a model system to study complex pathogens. | in the last few years, a wealth of information has become available relating to the targets of vaccinia virus (vacv)-specific cd4(+) t cell, cd8(+) t cell and antibody responses. due to the large size of its genome, encoding more than 200 different proteins, vacv represents a useful model system to study immunity to complex pathogens. our data demonstrate that both cellular and humoral responses target a large number of antigens and epitopes. this broad spectrum of targets is detected in both mi ... | 2009 | 20006135 |
| ocular vaccinia with severe restriction of extraocular motility. | 2009 | 20008731 | |
| jx-594, a targeted oncolytic poxvirus for the treatment of cancer. | jx-594 is a replication-competent wyeth strain vaccinia virus that was genetically modified to inactive the endogenous thymidine kinase gene and to express human gm-csf and lacz genes. in development by jennerex inc and licensee green cross corp, the modified virus is a novel therapy for treatment-refractive metastatic malignancies from various sites of origin. targeted oncolytic virotherapy has demonstrated promise in preclinical studies, and more than ten viral species have subsequently entere ... | 2009 | 19943208 |
| original encounter with antigen determines antigen-presenting cell imprinting of the quality of the immune response in mice. | obtaining a certain multi-functionality of cellular immunity for the control of infectious diseases is a burning question in immunology and in vaccine design. early events, including antigen shuttling to secondary lymphoid organs and recruitment of innate immune cells for adaptive immune response, determine host responsiveness to antigens. however, the sequence of these events and their impact on the quality of the immune response remain to be elucidated. here, we chose to study modified vaccini ... | 2009 | 19997562 |
| development of a cytotoxic t-cell assay in rabbits to evaluate early immune response to human t-lymphotropic virus type 1 infection. | human t-lymphotropic virus type 1 (htlv-1) infection causes adult t-cell lymphoma/leukemia (atl) following a prolonged clinical incubation period, despite a robust adaptive immune response against the virus. early immune responses that allow establishment of the infection are difficult to study without effective animal models. we have developed a cytotoxic t-lymphocyte (ctl) assay to monitor the early events of htlv-1 infection in rabbits. rabbit skin fibroblast cell lines were established by tr ... | 2009 | 19951176 |