Publications

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
double-stranded rna-dependent protein kinase-dependent apoptosis induction by a novel small compound.	the interferon-induced, double-stranded rna-dependent protein kinase (pkr) can play critical roles in inhibiting virus replication and inducing apoptosis. to develop new agents that may inhibit viral replication or induce apoptosis in cancer cells via the pkr signaling pathway, we screened a chemical library for compounds that have differential cytotoxic effects on wild-type [mouse embryonic fibroblast (mef)/pkr(+/+)] and pkr-knockout [mef/pkr(-/-)] mouse embryonic fibroblast cells. we identifie ...	2009	19066342
comparison of the safety and immunogenicity of acam1000, acam2000 and dryvax in healthy vaccinia-naive adults.	currently, more than half of the world's population has no immunity against smallpox variola major virus. this phase i double-blind, randomized trial was conducted to compare the safety and immunogenicity of two clonally derived, cell-culture manufactured vaccinia strains, acam1000 and acam2000, to the parent vaccine, dryvax. thirty vaccinia-naïve subjects were enrolled into each of three groups and vaccines were administered percutaneously using a bifurcated needle at a dose of 1.0x10(8)pfu/ml. ...	2009	19071184
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
lower levels of gamma interferon expressed by a pseudotyped single-cycle simian immunodeficiency virus enhance immunogenicity in rats.	a vaccine for human immunodeficiency virus (hiv) infection is desperately needed to control the aids pandemic. to address this problem, we constructed single-cycle simian immunodeficiency viruses (sivs) pseudotyped with the glycoprotein of vesicular stomatitis virus and expressing different levels of gamma interferon (ifn-gamma) as a potential vaccine strategy. we previously showed that ifn-gamma expression by pseudotyped sivs does not alter viral single-cycle infectivity. t cells primed with de ...	2009	19073726
vaccinia virus-mediated inhibition of type i interferon responses is a multifactorial process involving the soluble type i interferon receptor b18 and intracellular components.	poxviruses such as virulent vaccinia virus (vacv) strain western reserve encode a broad range of immune modulators that interfere with host responses to infection. upon more than 570 in vitro passages in chicken embryo fibroblasts (cef), chorioallantois vacv ankara (cva) accumulated mutations that resulted in highly attenuated modified vaccinia virus ankara (mva). mva infection of mice and of dendritic cells (dc) induced significant type i interferon (ifn) responses, whereas infection with vacv ...	2009	19073732
membrane remodelling during vaccinia virus morphogenesis.	vacv (vaccinia virus) is one of the most complex viruses, with a size exceeding 300 nm and more than 100 structural proteins. its assembly involves sequential interactions and important rearrangements of its structural components.	2009	19076058
atopic dermatitis: a disease caused by innate immune defects?	atopic dermatitis (ad) is a common chronic inflammatory skin disease that has increased in prevalence over the last half century. a growing body of evidence suggests that there are a variety of defects in the innate immune system that collectively affect the development and severity of ad. the reduction in antimicrobial peptides, diminished recruitment of innate immune cells (pmns, pdc, and nk cells) to the skin, epithelial barrier disruption, and tlr2 defects are just some of the credible expla ...	2009	19078985
ifn-alpha-mediated increase in cytolytic activity of maturing nk cell upon exposure to hsv-infected myelomonocytes.	impaired control of chronic pathogen replication may be associated to alterations of nk-cell function. whether mechanisms underlying this dysfunction involve perturbations of differentiating nk cells is still unknown. we studied an "in vitro" model of differentiation from cd34(+)lin(-) precursors growing only myelomonocytes and maturing nk cells and where myelomonocytes could be suitably infected with hsv, hiv, or vaccinia. cultures were evaluated by cytofluorometry and cytotoxicity assays for p ...	2009	19089810
imvamune: modified vaccinia ankara strain as an attenuated smallpox vaccine.	smallpox vaccines based on replicating vaccinia virus are known to elicit rare yet serious adverse events, particularly in human populations with immune deficiency, atopic dermatitis and at the extremes of age. a vaccine that induces protective immune responses equivalent to first-generation smallpox vaccines while reducing the risk for severe adverse events is critical for a national stockpile of smallpox vaccines. modified vaccinia ankara (mva) has been proposed as an immediate solution for va ...	2009	19093767
a prime/boost dna/modified vaccinia virus ankara vaccine expressing recombinant leishmania dna encoding tryp is safe and immunogenic in outbred dogs, the reservoir of zoonotic visceral leishmaniasis.	previous studies demonstrated safety, immunogenicity and efficacy of dna/modified vaccinia virus ankara (mva) prime/boost vaccines expressing tryparedoxin peroxidase (tryp) and leishmania homologue of the mammalian receptor for activated c kinase (lack) against leishmania major challenge in mice, which was consistent with results from tryp protein/adjuvant combinations in non-human primates. this study aimed to conduct safety and immunogenicity trials of these dna/mva vaccines in dogs, the natur ...	2009	19095029
gene gun-supported dna immunisation of chicken for straightforward production of poxvirus-specific igy antibodies.	orthopoxviruses code for numerous immunomodulatory proteins, the structure and function of which are clarified inadequately. antibodies constitute a potent tool to study such proteins, enabling conclusions on protein location and time course of expression. however, common antibody production in mice or rabbits requires tedious protein expression and injection, as well as blood collection at regular intervals. to simplify this procedure, igy antibodies specific for poxviral proteins (f1l and p28) ...	2009	19100269
targeted and armed oncolytic poxviruses: a novel multi-mechanistic therapeutic class for cancer.	viruses have been engineered for cancer therapy in a variety of ways. approaches include non-replicating gene therapy vectors, cancer vaccines and oncolytic viruses, but the clinical efficacy of these approaches has been limited by multiple factors. however, a new therapeutic class of oncolytic poxviruses has recently been developed that combines targeted and armed approaches for treating cancer. initial preclinical and clinical results show that products from this therapeutic class can systemic ...	2009	19104515
reconciling contradictory reports regarding translation of bace1 mrna: initiation mechanism is altered by different expression systems.	we previously showed that translation from the rat bace1 5' leader is cap-dependent and that four aug codons (aug1-4) in the 5' leader were bypassed, partially or completely, depending on the cell line. two other groups reported comparable results with human bace1 sequences in different cell lines, although different mechanisms were postulated. in contrast, a third group working with the human sequence reported that most translation events are initiated at aug2. using reporter constructs with th ...	2009	19106624
a role for the host coatomer and kdel receptor in early vaccinia biogenesis.	members of the poxvirus family have been investigated for their applications as vaccines and expression vectors and, more recently, because of concern for their potential as biological weapons. vaccinia virus, the prototypic member, evolves through multiple forms during its replication. here, we show a surprising way by which vaccinia hijacks coatomer for early viral biogenesis. whereas coatomer forms copi vesicles in the host early secretory system, vaccinia formation bypasses this role of coat ...	2009	19109439
zoonotic vaccinia virus: clinical and immunological characteristics in a naturally infected patient.	vaccinia virus was used as vaccine to eradicate smallpox. we report a zoonotic case of vaccinia virus infection in a 30-year-old patient who became infected after handling sick dairy cattle. the patient had inflamed lesions and systemic symptoms. laboratory findings were indicative of down-modulated immune responses to the virus.	2009	19115976
risks associated with vaccinia virus in the laboratory.	vaccinia virus (vacv) is used commonly in research laboratories. non-highly attenuated strains of vacv are potentially pathogenic in humans, and vacv vaccination and biosafety level 2 facilities and protocols are currently recommended for vaccinated laboratory workers in the united states who handle non-highly attenuated strains of the virus. despite this, laboratory-related vacv exposures continue to occur and a number of recent instances of vacv infection in non-vaccinated laboratory workers h ...	2009	19118854
phase ii trial of modified vaccinia ankara (mva) virus expressing 5t4 and high dose interleukin-2 (il-2) in patients with metastatic renal cell carcinoma.	interleukin-2 (il-2) induces durable objective responses in a small cohort of patients with metastatic renal cell carcinoma (rcc) but the antigen(s) responsible for tumor rejection are not known. 5t4 is a non-secreted membrane glycoprotein expressed on clear cell and papillary rccs. a modified vaccinia virus ankara (mva) encoding 5t4 was tested in combination with high-dose il-2 to determine the safety, objective response rate and effect on humoral and cell-mediated immunity.	2009	19128501
inhibition of the ubiquitin-proteasome system prevents vaccinia virus dna replication and expression of intermediate and late genes.	the ubiquitin-proteasome system has a central role in the degradation of intracellular proteins and regulates a variety of functions. viruses belonging to several different families utilize or modulate the system for their advantage. here we showed that the proteasome inhibitors mg132 and epoxomicin blocked a postentry step in vaccinia virus (vacv) replication. when proteasome inhibitors were added after virus attachment, early gene expression was prolonged and the expression of intermediate and ...	2009	19129442
modified vaccinia virus ankara triggers chemotaxis of monocytes and early respiratory immigration of leukocytes by induction of ccl2 expression.	orthopoxviruses commonly enter into humans and animals via the respiratory tract. herein, we show that immigration of leukocytes into the lung is triggered via intranasal infection of mice with modified vaccinia virus ankara (mva) and not with the vaccinia virus (vacv) elstree, wyeth, or western reserve (wr) strain. immigrating cells were identified as monocytes, neutrophils, and cd4(+) lymphocytes by flow cytometry and could be detected 24 h and 48 h postinfection. using an in vitro chemotaxis ...	2009	19129447
long-term vaccine protection from aids and clearance of viral dna following shiv89.6p challenge.	in an earlier study, our group vaccinated rhesus macaques with vesicular stomatitis virus (vsv) vectors expressing gag, pol, and env proteins from a hybrid simian/human immunodeficiency virus (shiv). this was followed by a single boost with modified vaccinia virus ankara (mva) vectors expressing the same proteins. following challenge with shiv89.6p, vaccinated animals cleared challenge virus rna from the blood by day 150 and maintained normal cd4 t cell counts for 8 months. here we report on the ...	2009	19135115
the kinase activity of pseudorabies virus us3 is required for modulation of the actin cytoskeleton.	different viruses exploit the host cytoskeleton to facilitate replication and spread. the conserved us3 protein of the alphaherpesvirus pseudorabies virus induces actin stress fiber disassembly and formation of actin-containing cell projections, which are associated with enhanced intercellular virus spread. proteins of members of other virus families, notably vaccinia virus f11l protein and human immunodeficiency virus nef protein, induce actin rearrangements that are very similar to those induc ...	2009	19136132
regression of human pancreatic tumor xenografts in mice after a single systemic injection of recombinant vaccinia virus glv-1h68.	oncolytic virotherapy of tumors has shown promising results in both preclinical and clinical studies. here, we investigated the therapeutic efficacy of a replication-competent vaccinia virus, glv-1h68, against human pancreatic carcinomas in cell cultures and in nude mice. we found that glv-1h68 was able to infect, replicate in, and lyse tumor cells in vitro. virus-mediated marker gene expressions were readily detected. moreover, s.c. panc-1 pancreatic tumor xenografts were effectively treated by ...	2009	19139123
broad, high-magnitude and multifunctional cd4+ and cd8+ t-cell responses elicited by a dna and modified vaccinia ankara vaccine containing human immunodeficiency virus type 1 subtype c genes in baboons.	candidate human immunodeficiency virus (hiv) vaccine regimens based on dna boosted with recombinant modified vaccinia ankara (mva) have been in development for some time, and there is evidence for improved immunogenicity of newly developed constructs. this study describes immune responses to candidate dna and mva vaccines expressing multiple genes (gag, rt, tat, nef and env) from hiv-1 subtype c in chacma baboons (papio ursinus). the vaccine regimen induced (i) strong t-cell responses, with a me ...	2009	19141458
the heterogeneity of human antibody responses to vaccinia virus revealed through use of focused protein arrays.	the renewed interest in strategies to combat infectious agents with epidemic potential has led to a re-examination of vaccination protocols against smallpox. to help define which antigens elicit a human antibody response, we have targeted proteins known or predicted to be presented on the surface of the intracellular mature virion (imv) or the extracellular enveloped virion (eev). the predicted ectodomains were expressed in a mammalian in vitro coupled transcription/translation reaction using tr ...	2009	19146908
aim2 recognizes cytosolic dsdna and forms a caspase-1-activating inflammasome with asc.	the innate immune system senses nucleic acids by germline-encoded pattern recognition receptors. rna is sensed by toll-like receptor members tlr3, tlr7 and tlr8, or by the rna helicases rig-i (also known as ddx58) and mda-5 (ifih1). little is known about sensors for cytoplasmic dna that trigger antiviral and/or inflammatory responses. the best characterized of these responses involves activation of the tank-binding kinase (tbk1)-interferon regulatory factor 3 (irf3) signalling axis to trigger tr ...	2009	19158675
a novel replication-competent vaccinia vector mvtt is superior to mva for inducing high levels of neutralizing antibody via mucosal vaccination.	mucosal vaccination offers great advantage for inducing protective immune response to prevent viral transmission and dissemination. here, we report our findings of a head-to-head comparison of two viral vectors modified vaccinia ankara (mva) and a novel replication-competent modified vaccinia tian tan (mvtt) for inducing neutralizing antibodies (nabs) via intramuscular and mucosal vaccinations in mice. mvtt is an attenuated variant of the wild-type vtt, which was historically used as a smallpox ...	2009	19159014
self-assembly of sapovirus recombinant virus-like particles from polyprotein in mammalian cells.	the sav genome is a positive-sense, non-segmented single-strand rna molecule of approximately 7.5 kb that is polyadenylated at its 3' terminus. the major capsid (vp1) of sav is thought to be produced as the orf1 polyprotein followed by cleavage, or translation from subgenomic rna (3'-coterminal with the virus genome), or both. we have recently reported the formation of sav vlp from subgenomic-like rna in mammalian cells. in the present study, we demonstrated that the vp1 cleaved from a part of o ...	2009	19161558
vaccinia virus l1 binds to cell surfaces and blocks virus entry independently of glycosaminoglycans.	l1 and a28 are vaccinia virus (vacv) envelope proteins which are essential for cellular entry. however, their specific roles during entry are unknown. we tested whether one or both of these proteins might serve as receptor binding proteins (rbp). we found that a soluble, truncated form of l1, but not a28, bound to cell surfaces independently of glycosaminoglycans (gags). hence, vacv a28 is not likely to be a rbp and functions after attachment during entry. importantly, soluble l1 inhibited both ...	2009	19162289
vaccinia virus exhibits cell-type-dependent entry characteristics.	differing and sometimes conflicting data have been reported regarding several aspects of vaccinia virus (vv) entry. to address this, we used a beta-galactosidase reporter virus to monitor virus entry into multiple cell types under varying conditions. entry into hela, b78h1 and l cells was strongly inhibited by heparin whereas entry into vero and bsc-1 cells was unaffected. bafilomycin also exhibited variable and cell-type-specific effects on vv entry. entry into b78h1 and bsc-1 cells was strongl ...	2009	19162290
immunogenicity of recombinant modified vaccinia ankara following a single or multi-dose vaccine regimen in rhesus monkeys.	modified vaccinia ankara (mva) is a replication-defective strain of vaccinia virus (vv) that is being investigated in humans as an alternative vaccine against smallpox. understanding the parameters of a mva vaccine regimen that can effectively enhance protective immunity will be important for clinical development. the present studies utilize cohorts of rhesus monkeys immunized with recombinant mva (rmva) or recombinant vv (rvv) vaccine vectors to investigate the magnitude, breadth, and durabilit ...	2009	19168105
organ-specific attenuation of murine hepatitis virus strain a59 by replacement of catalytic residues in the putative viral cyclic phosphodiesterase ns2.	the murine hepatitis virus (mhv) strain a59 ns2 protein is a 30-kda nonstructural protein that is expressed from a subgenomic mrna in the cytoplasm of virus-infected cells. its homologs are also encoded in other closely related group 2a coronaviruses and more distantly related toroviruses. together, these proteins comprise a subset of a large superfamily of 2h phosphoesterase proteins that are distinguished by a pair of conserved his-x-thr/ser motifs encompassing catalytically important residues ...	2009	19176619
generation of recombinant vaccinia viruses via green fluorescent protein selection.	we developed a rapid method to generate recombinant vaccinia viruses (rvvs) based upon a bicistronic cassette encoding the gene for green fluorescent protein (gfp) and a foreign gene of interest separated by an internal ribosome entry site (ires). as proof-of-concept, we inserted a mutant env gene of human immunodeficiency virus (hiv) into the cassette, which was cloned into the vaccinia virus (vv) insertion vector psc59 under the control of the early-late vv synthetic promoter and flanked by di ...	2009	19182996
in vitro and in vivo differentiated effector cd8 t cells display divergent histone acetylation patterns within the ifng locus.	epigenetic remodeling of genes encoding effector cytokines that permit accessibility to the transcriptional machinery is a central event in the differentiation of naive t cells into effectors that can attack pathogens and tumors. covalent modifications of histones that cause a loosening of nucleosomal structures occur not only in promoter regions, but also at upstream and downstream enhancer elements that integrate various cellular stimuli to modulate the rate of transcriptional initiation. this ...	2009	19195486
gender effects on humoral immune responses to smallpox vaccine.	there are no data currently available on gender and racial variation in smallpox vaccine immune responses. we recruited 1076 healthy adults 18-40 years old who received one dose of the us-licensed smallpox vaccine (dryvax). vaccinia neutralizing antibody titers in each subject's serum were determined using a high throughput neutralization assay based on a recombinant, beta-gal expressing vaccinia virus. results are reported as the serum dilution inhibiting 50% of virus activity (id(50)). the med ...	2009	19200827
recombinant measles viruses expressing single or multiple antigens of human immunodeficiency virus (hiv-1) induce cellular and humoral immune responses.	recombinant measles viruses (rmv) based on the live attenuated measles vaccine strain (mvb) expressing antigens of hiv-1 clade b were generated by reverse genetics. recombinants expressing single or double antigens of hiv-1 (rmv-hiv) were genetically highly stable on human diploid cells. the production process of these viruses was essentially similar to the parental mv strain, yielding comparative end titers. immunization of tg-mice by different regimens and formulations showed potent humoral an ...	2009	19200842
an e2-f12 complex is required for intracellular enveloped virus morphogenesis during vaccinia infection.	the vaccinia virus protein, f12, has been suggested to play an important role in microtubule-based transport of intracellular enveloped virus (iev). we found that gfp-f12 is recruited to iev moving on microtubules but is released from virus particles when they switch to actin-based motility. in the absence of f12, although the majority of iev remain close to their peri-nuclear site of assembly, a small number of iev still move with linear trajectories at speeds of 0.85 μm s(-1) , consistent with ...	2009	19207726
sars-cov spike proteins expressed by the vaccinia virus tiantan strain: secreted sq protein induces robust neutralization antibody in mice.	the spike (s) glycoprotein of severe acute respiratory syndrome coronavirus (sars-cov) is a major target in the development of diagnostic assays and vaccines, but its antigenic and immunogenic properties remain unclear. seven sars-cov spike proteins (s, sq, s1, rbd, s2, s2q, and cx) were generated using the modified vaccinia virus (tiantan strain) as a vector, and their antigenicity and immunogenicity were evaluated. the secreted sq protein in which the transmembrane domain was deleted, as well ...	2009	19210229
characterization of the vaccinia virus d10 decapping enzyme provides evidence for a two-metal-ion mechanism.	decapping enzymes are required for the removal of the 5'-end cap of mrnas. these enzymes exhibit a specific hydrolase activity, resulting in cleavage between the alpha- and beta-phosphates of the m7gpppn cap to generate both m7gdp and monophosphorylated rna products. decapping enzymes have been found in humans, plants and yeasts, and have been discovered more recently in vaccinia virus (d10 protein). although experimental evidences are lacking, three-metal- and two-metal-ion mechanisms have been ...	2009	19210265
dimeric quaternary structure of the prototypical dual specificity phosphatase vh1.	the vaccinia virus h1 gene product, vh1, is a dual specificity phosphatase that down-regulates the cellular antiviral response by dephosphorylating stat1. the crystal structure of vh1, determined at 1.32 a resolution, reveals a novel dimeric quaternary structure, which exposes two active sites spaced approximately 39 a away from each other. vh1 forms a stable dimer via an extensive domain swap of the n-terminal helix (residues 1-20). in vitro, vh1 can dephosphorylate activated stat1, in a reacti ...	2009	19211553
essential role for either trs1 or irs1 in human cytomegalovirus replication.	viral infections often produce double-stranded rna (dsrna), which in turn triggers potent antiviral responses, including the global repression of protein synthesis mediated by protein kinase r (pkr) and 2'-5' oligoadenylate synthetase (oas). as a consequence, many viruses have evolved genes, such as those encoding dsrna-binding proteins, which counteract these pathways. human cytomegalovirus (hcmv) encodes two related proteins, ptrs1 and pirs1, which bind dsrna and can prevent activation of the ...	2009	19211736
poxvirus host range protein cp77 contains an f-box-like domain that is necessary to suppress nf-kappab activation by tumor necrosis factor alpha but is independent of its host range function.	tumor necrosis factor alpha (tnf-alpha) activates the nuclear factor kappab (nf-kappab) signaling pathway that regulates expression of many cellular factors playing important roles in innate immune responses and inflammation in infected hosts. poxviruses employ many strategies to inhibit nf-kappab activation in cells. in this report, we describe a poxvirus host range protein, cp77, which blocked nf-kappab activation by tnf-alpha. immunofluorescence analyses revealed that nuclear translocation of ...	2009	19211746
pi3k signaling regulates rapamycin-insensitive translation initiation complex formation in vaccinia virus-infected cells.	how vaccinia virus (vv) regulates assembly of the host translation initiation complex eif4f remains unclear. here, we show that vv activated host pi3k to stimulate downstream mammalian target of rapamycin (mtor), a kinase that inactivates the translational repressor 4e-bp1. however, although the mtor inhibitor rapamycin suppressed vv-induced inactivation of 4e-bp1, it failed to inhibit eif4f assembly. in contrast, pi3k inhibition in vv-infected cells increased the abundance of hypophosphorylated ...	2009	19211763
gamma interferon-induced interferon regulatory factor 1-dependent antiviral response inhibits vaccinia virus replication in mouse but not human fibroblasts.	vaccinia virus (vacv) replicates in mouse and human fibroblasts with comparable kinetics and efficiency, yielding similar titers of infectious progeny. here we demonstrate that gamma interferon (ifn-gamma) but not ifn-alpha or ifn-beta pretreatment of mouse fibroblasts prior to vacv infection induces a long-lasting antiviral state blocking vacv replication. in contrast, high doses of ifn-gamma failed to establish an antiviral state in human fibroblasts. in mouse fibroblasts, ifn-gamma impeded th ...	2009	19211768
expression and characterization of bovine lactoperoxidase by recombinant vaccinia virus.	lactoperoxidase (lpo) is a 78 kda heme-containing oxidation-reduction enzyme present in milk, found in physiological fluids of mammals. lpo has an antimicrobial activity, and presumably contribute to the protective functions of milk against infectious diseases. in this study, recombinant vaccinia virus expressing bovine lpo (vv/blpo) was constructed. in rabbit kidney (rk13) cells infected with vv/blpo, recombinant blpo was detected in both cell extracts and culture supernatants. tunicamycin trea ...	2009	19214766
expression of the highly conserved vaccinia virus e6 protein is required for virion morphogenesis.	the vaccinia virus e6r gene (vacvwr062) is conserved in all members of the poxvirus family and encodes a protein associated with the mature virion. we confirmed this association and provided evidence for an internal location. an inducible mutant that conditionally expresses e6 was constructed. in the absence of inducer, plaque formation and virus production were severely inhibited in several cell lines, whereas some replication occurred in others. this difference could be due to variation in the ...	2009	19217136
investigation of orf virus structure and morphogenesis using recombinants expressing flag-tagged envelope structural proteins: evidence for wrapped virus particles and egress from infected cells.	orf virus (orfv) is the type species of the genus parapoxvirus, but little is known about the structure or morphogenesis of the virus. in contrast, the structure and morphogenesis of vaccinia virus (vacv) has been extensively studied. vacv has two main infectious forms, mature virion (mv) and extracellular virion (ev). the mv is wrapped by two additional membranes derived from the trans-golgi to produce a wrapped virion (wv), the outermost of which is lost by cellular membrane fusion during vira ...	2009	19218206
high-affinity human leucocyte antigen class i binding variola-derived peptides induce cd4+ t cell responses more than 30 years post-vaccinia virus vaccination.	interferon-gamma secreting t lymphocytes against pox virus-derived synthetic 9-mer peptides were tested by enzyme-linked immunospot in peripheral blood of individuals vaccinated with vaccinia virus more than 30 years ago. the peptides were characterized biochemically as high-affinity human leucocyte antigen (hla) class i binders (k(d) <or= 5 nm). however, five of the individuals tested did not show typical cd8(+) t cell-mediated hla class i-restricted responses. instead, these donors showed cd4( ...	2009	19220834
interleukin-18-related genes are induced during the contraction phase but do not play major roles in regulating the dynamics or function of the t-cell response to listeria monocytogenes infection.	proinflammatory cytokines, such as gamma interferon (ifn-gamma), impact aspects of t-cell responses after infection, including expansion, contraction, and memory formation. interleukin-18 (il-18) functions as a proinflammatory cytokine by stimulating the production of ifn-gamma from multiple cell types and accentuating the development of th1 cd4 t-cell responses. focused microarray analyses revealed upregulation of il-18 and il-18 receptor genes in cd8 t cells during the contraction phase. based ...	2009	19223481
correlates of protection efficacy induced by vaccinia virus-specific cd8+ t-cell epitopes in the murine intranasal challenge model.	the recent identification of a large array of different vaccinia virus-derived cd8(+) t-cell epitopes offers a unique opportunity to systematically analyze the correlation between protective efficacy and variables such as kinetics of expression and function of viral proteins, binding affinity to mhc molecules, immunogenicity, and viral antigen processing/presentation. in the current study, 49 different h-2(b) restricted epitopes were tested for their ability to protect peptide-immunized c57bl/6 ...	2009	19224639
the 3'-to-5' exonuclease activity of vaccinia virus dna polymerase is essential and plays a role in promoting virus genetic recombination.	poxviruses are subjected to extraordinarily high levels of genetic recombination during infection, although the enzymes catalyzing these reactions have never been identified. however, it is clear that virus-encoded dna polymerases play some unknown yet critical role in virus recombination. using a novel, antiviral-drug-based strategy to dissect recombination and replication reactions, we now show that the 3'-to-5' proofreading exonuclease activity of the viral dna polymerase plays a key role in ...	2009	19224992
[examination of biocides for their effectiveness against animal viruses according to european union standards with emphasis on the selection of a suitable test virus].	because of the changes to be expected in the methods for testing disinfectants deemed to be used in the veterinary field, candidate viral species were evaluated for their suitability as test virus. considered viral species included different non-enveloped viruses [bovine enterovirus type 1 (ecbo (enteric cytopathogenic bovine orphan) virus), mammalian reovirus type 1, feline calici virus (fcv), and bovine parvovirus (bpv)], as well as enveloped viruses, as equine arteritisvirus (eav), bovine her ...	2009	19226936
cutting edge: mucosal application of a lyophilized viral vector vaccine confers systemic and protective immunity toward intracellular pathogens.	a major problem of current vaccines is storage stability, often requiring strict maintenance of cold chains. in the course of the eradication of smallpox, a freeze-dried vaccinia virus (dryvax), which proved to be very stable, was used to overcome this limitation. however, dryvax needs to be reconstituted before usage and is administered using a bifurcated needle, procedures that pose a number of additional health risks. we report in this study that a stable, lyophilized, modified vaccinia virus ...	2009	19234150
programming for cd8 t cell memory development requires il-12 or type i ifn.	inflammation can have both positive and negative effects on development of cd8 t cell memory, but the relative contributions and cellular targets of the cytokines involved are unclear. using cd8 t cells lacking receptors for il-12, type i ifn, or both, we show that these cytokines act directly on cd8 t cells to support memory formation in response to vaccinia virus and listeria monocytogenes infections. development of memory to vaccinia is supported predominantly by il-12, whereas both il-12 and ...	2009	19234173
preferential use of b7.2 and not b7.1 in priming of vaccinia virus-specific cd8 t cells.	recent studies have demonstrated that cd28 provides critical costimulatory signals required for optimal cd8 t cell expansion and effector function in response to several viruses, including influenza, hsv, and vaccinia virus (vacv). cd28 has two ligands expressed largely on professional apc, named b7.1 (cd80) and b7.2 (cd86). although some results suggest that these ligands are equivalent and both promote cd28 signaling, it is not clear whether they are equally important for priming of antiviral ...	2009	19234186
fas ligand is required for the development of respiratory syncytial virus vaccine-enhanced disease.	children immunized with a formalin-inactivated respiratory syncytial virus (rsv) vaccine experienced enhanced disease and exhibited pulmonary eosinophilia upon natural rsv infection. balb/c mice immunized with either formalin-inactivated rsv or a recombinant vaccinia virus (vacv) expressing the rsv attachment (g) protein develop extensive pulmonary eosinophilia after rsv challenge that mimics the eosinophilic response observed in the children during the 1960s vaccine trials. fas ligand (fasl) is ...	2009	19234198
vaccinia virus-based multivalent h5n1 avian influenza vaccines adjuvanted with il-15 confer sterile cross-clade protection in mice.	the potential for a global influenza pandemic remains significant with epidemiologic and ecologic indicators revealing the entrenchment of the highly pathogenic avian influenza a h5n1 in both wild bird populations and domestic poultry flocks in asia and in many african and european countries. indisputably, the single most effective public health intervention in mitigating the devastation such a pandemic could unleash is the availability of a safe and effective vaccine that can be rapidly deploye ...	2009	19234203
preclinical and clinical development of a multi-envelope, dna-virus-protein (d-v-p) hiv-1 vaccine.	the human immune system has evolved to recognize antigenic diversity, a strength that has been harnessed by vaccine developers to combat numerous pathogens (e.g., pneumococcus, influenza virus, rotavirus). in each case, vaccine cocktails were formulated to include antigenic variants of the target. to combat hiv-1 diversity, we assembled a cocktail vaccine comprising dozens of envelopes, delivered as recombinant dna, vaccinia virus, and protein for testing in a clinical trial. one vaccinee has no ...	2009	19241253
natural human infections with vaccinia virus during bovine vaccinia outbreaks.	bovine vaccinia is an exanthematic disease caused by vaccinia virus (vacv). this zoonosis has been associated with several cases of bovine infection, particularly in milk herds. farmers, milkers and their close contacts developed lesions on the hands, forearms, legs and face accompanied by fever, headache, malaise, myalgia and axillary, inguinal and cervical lymphadenopathy. vacv infections have a significant public health impact due to their occupational character, high frequency of transmissio ...	2009	19243990
dideoxy fluoro-ketopyranosyl nucleosides as potent antiviral agents: synthesis and biological evaluation of 2,3- and 3,4-dideoxy-3-fluoro-4- and -2-keto-beta-d-glucopyranosyl derivatives of n(4)-benzoyl cytosine.	the synthesis of the dideoxy fluoro ketopyranonucleoside analogues, 1-(2,3-dideoxy-3-fluoro-6-o-trityl-beta-d-glycero-hexopyranosyl-4-ulose)-n(4)-benzoyl cytosine (7a), 1-(3,4-dideoxy-3-fluoro-6-o-trityl-beta-d-glycero-hexopyranosyl-2-ulose)-n(4)-benzoyl cytosine (13a) and their detritylated analogues 8a and 14a, respectively, is described. condensation of peracetylated 3-deoxy-3-fluoro-d-glucopyranose (1) with silylated n(4)-benzoyl cytosine, followed by selective deprotection and isopropyliden ...	2009	19246130
generating aptamers for recognition of virus-infected cells.	the development of molecular probes capable of recognizing virus-infected cells is essential to meet the serious clinical, therapeutic, and national-security challenges confronting virology today. we report the development of dna aptamers as probes for the selective targeting of virus-infected living cells.	2009	19246617
mamu-a01/k(b) transgenic and mhc class i knockout mice as a tool for hiv vaccine development.	we have developed a murine model expressing the rhesus macaque (rm) mamu-a01 mhc allele to characterize immune responses and vaccines based on antigens of importance to human disease processes. towards that goal, transgenic (tg) mice expressing chimeric rm (alpha1 and alpha2 mamu-a01 domains) and murine (alpha3, transmembrane, and cytoplasmic h-2k(b) domains) mhc class i molecules were derived by transgenesis of the h-2k(b)d(b) double mhc class i knockout strain. after immunization of mamu-a01/k ...	2009	19249807
preparation of recombinant viral glycoproteins for novel and therapeutic antibody discovery.	neutralizing antibodies are a critical component in the protection or recovery from viral infections. in the absence of available vaccines or antiviral drugs for many important human viral pathogens, the identification and characterization of new human monoclonal antibodies (hmabs) that are able to neutralize viruses offers the possibility for effective pre- and/or post-exposure therapeutic modalities. such hmabs may also help in our understanding of the virus entry process, the mechanisms of vi ...	2009	19252850
engineering the vaccinia virus l1 protein for increased neutralizing antibody response after dna immunization.	the licensed smallpox vaccine, comprised of infectious vaccinia virus, has associated adverse effects, particularly for immunocompromised individuals. therefore, safer dna and protein vaccines are being investigated. the l1 protein, a component of the mature virion membrane that is conserved in all sequenced poxviruses, is required for vaccinia virus entry into host cells and is a target for neutralizing antibody. when expressed by vaccinia virus, the unglycosylated, myristoylated l1 protein att ...	2009	19257896
the rate of n-wasp exchange limits the extent of arp2/3-complex-dependent actin-based motility.	understanding cell motility will require detailed knowledge not only of the localization of signalling networks regulating actin polymerization, but also of their dynamics. unfortunately, many signalling networks are not amenable to such analysis, as they are frequently transient and dispersed. by contrast, the signalling pathways used by pathogens undergoing actin-based motility are highly localized and operate in a constitutive fashion. taking advantage of this, we have analysed the dynamics o ...	2009	19262673
smallpox virus plaque phenotypes: genetic, geographical and case fatality relationships.	smallpox (infection with orthopoxvirus variola) remains a feared illness more than 25 years after its eradication. historically, case-fatality rates (cfrs) varied between outbreaks (<1 to approximately 40 %), the reasons for which are incompletely understood. the extracellular enveloped virus (eev) form of orthopoxvirus progeny is hypothesized to disseminate infection. investigations with the closely related orthopoxvirus vaccinia have associated increased comet formation (eev production) with i ...	2009	19264626
acidic residues in the membrane-proximal stalk region of vaccinia virus protein b5 are required for glycosaminoglycan-mediated disruption of the extracellular enveloped virus outer membrane.	the extracellular enveloped virus (eev) form of vaccinia virus (vacv) is surrounded by two lipid envelopes. this presents a topological problem for virus entry into cells, because a classical fusion event would only release a virion surrounded by a single envelope into the cell. recently, we described a mechanism in which the eev outer membrane is disrupted following interaction with glycosaminoglycans (gags) on the cell surface and thus allowing fusion of the inner membrane with the plasma memb ...	2009	19264647
contribution of nonneutralizing vaccine-elicited antibody activities to improved protective efficacy in rhesus macaques immunized with tat/env compared with multigenic vaccines.	previously, chronic-phase protection against shiv(89.6p) challenge was significantly greater in macaques primed with replicating adenovirus type 5 host range mutant (ad5hr) recombinants encoding hivtat and env and boosted with tat and env protein compared with macaques primed with multigenic adenovirus recombinants (hivtat, hivenv, sivgag, sivnef) and boosted with tat, env, and nef proteins. the greater protection was correlated with tat- and env-binding abs. because the macaques lacked shiv(89. ...	2009	19265150
increased detection of proliferating, polyfunctional, hiv-1-specific t cells in dna-modified vaccinia virus ankara-vaccinated human volunteers by cultured ifn-gamma elispot assay.	induction of a long-term immunological memory, which can expand and defend the host upon pathogen encounter, is the "holy grail" of vaccinology. here, using a sensitive cultured ifn-gamma elispot assay, we show that 50% (15 out of 30) of healthy, hiv-1/2-uninfected volunteers who received pthr.hiva dna prime-modified vaccinia virus ankara. hiva boost vaccine regimen 1 to 3 1/2 years ago had detectable hiv-1-specific t-cell responses. these t cells, predominantly of the cd4(+) subtype, could prol ...	2009	19266489
highlights from the march 2009 issue of dna and cell biology.		2009	19267580
the antitumor and immunoadjuvant effects of ifn-alpha in combination with recombinant poxvirus vaccines.	ifn-alpha is a pleiotropic cytokine possessing immunomodulatory properties that may improve the efficacy of therapeutic cancer vaccines. the aim of this study was to evaluate the effectiveness and compatibility of combining recombinant ifn-alpha with poxvirus vaccines targeting the human carcinoembryonic antigen (cea) in murine models of colorectal and pancreatic adenocarcinomas, where cea is a self-antigen.	2009	19276249
clinical and immunological response to attenuated tissue-cultured smallpox vaccine lc16m8.	the attenuated, tissue-cultured, third-generation smallpox vaccine lc16m8 was administered to vaccinia-naive infants in japan during the 1970s without serious adverse events. it is a good candidate for use as part of a prevention plan for bioterrorism.	2009	19278946
nonreplicating vaccinia virus vectors expressing the h5 influenza virus hemagglutinin produced in modified vero cells induce robust protection.	the timely development of safe and effective vaccines against avian influenza virus of the h5n1 subtype will be of the utmost importance in the event of a pandemic. our aim was first to develop a safe live vaccine which induces both humoral and cell-mediated immune responses against human h5n1 influenza viruses and second, since the supply of embryonated eggs for traditional influenza vaccine production may be endangered in a pandemic, an egg-independent production procedure based on a permanent ...	2009	19279103
a novel recombinant vaccinia virus expressing the human norepinephrine transporter retains oncolytic potential and facilitates deep-tissue imaging.	noninvasive and repetitive monitoring of a virus in target tissues and/or specific organs of the body is highly desirable for the development of safe and efficient cancer virotherapeutics. we have previously shown that the oncolytic vaccinia virus glv-1h68 can target and eradicate human tumors in mice and that its therapeutic effects can be monitored by using optical imaging. here, we report on the development of a derivative of glv-1h68, a novel recombinant vaccinia virus (vacv) glv-1h99, which ...	2009	19287510
downregulation of vaccinia virus intermediate and late promoters by host transcription factor yy1.	approximately half of the intermediate and late gene transcriptional promoters of vaccinia virus have a binding site for the cellular transcription factor yy1 that overlaps the initiator elements. depletion of yy1 using rna interference enhanced the activity of these promoters, while overexpression of yy1 repressed their activity. viral promoter nucleotide replacements that specifically impair the binding of yy1 mostly alleviated the transcriptional repression and correlated with the ability of ...	2009	19297611
recall responses by helpless memory cd8+ t cells are restricted by the up-regulation of pd-1.	cd4 help is crucial for memory cd8(+) t cell development, yet the mechanisms of cd4 help and why (cd4) helpless memory cd8(+) t cells elicit poor recall responses are currently not well understood. in this study we investigated these questions using an in vivo acute virus infection model. we show herein that cd4 help during priming is required for memory cd8(+) t cell differentiation, and that stimulation of cd40 during priming rescues the helpless defects in the absence of cd4(+) t cells. the d ...	2009	19299723
inhibition of vaccinia virus replication by two small interfering rnas targeting b1r and g7l genes and their synergistic combination with cidofovir.	in view of the threat of the potential use of variola virus in a terrorist attack, considerable efforts have been performed to develop new antiviral strategies against orthopoxviruses. here we report on the use of rna interference, either alone or in combination with cidofovir, as an approach to inhibit orthopoxvirus replication. two selected small interfering rnas (sirnas), named sib1r-2 and sig7l-1, and a previously reported sirna, i.e., sid5r-2 (which targets the viral d5r mrna), were evaluat ...	2009	19307376
a functional type i topoisomerase from pseudomonas aeruginosa.	pseudomonas aeruginosa encodes a putative topoisomerase with sequence similarity to the eukaryotic type ib topoisomerase from vaccinia virus. residues in the active site are conserved, notably tyr292 which would be predicted to form the transient covalent bond to dna.	2009	19317906
protein kinase pkr-dependent activation of mitogen-activated protein kinases occurs through mitochondrial adapter ips-1 and is antagonized by vaccinia virus e3l.	the p38 and c-jun n-terminal kinase (jnk) mitogen-activated protein kinases (mapks) play important roles in the host innate immune response. the protein kinase regulated by rna (pkr) is implicated in p38 mapk activation in response to proinflammatory signals in mouse embryonic fibroblasts. to test the role of pkr in the activation of p38 and jnk mapks in human cells following viral infection, hela cells made stably deficient in pkr by using an rna interference strategy were compared to cells wit ...	2009	19321614
improved survival in rhesus macaques immunized with modified vaccinia virus ankara recombinants expressing simian immunodeficiency virus envelope correlates with reduction in memory cd4+ t-cell loss and higher titers of neutralizing antibody.	previous studies demonstrated that immunization of macaques with simian immunodeficiency virus (siv) gag-pol and env recombinants of the attenuated poxvirus modified vaccinia virus ankara (mva) provided protection from high viremia and aids following challenge with a pathogenic strain of siv. although all animals became infected, plasma viremia was significantly reduced in animals that received the mva-siv recombinant vaccines compared with animals that received nonrecombinant mva. most importan ...	2009	19321617
prime-boost vaccination using recombinant mycobacterium bovis bcg and recombinant vaccinia virus dis harboring hiv-1 crf01_ae gag in mice: influence of immunization routes.	we have previously reported that live vector-based hiv-1 gag vaccine candidate using bcg as a vector was achievable in balb/c mice. although the gag-specific ctl induced by this live candidate vaccine is significantly high, persistence of ctl remains unclear. thus, efforts were made to explore the potential of recombinant vaccinia virus dis strain harboring the same hiv-1 crf01_ae gag gene (rvaccinia/ hiv-1gage) present in the bcg construct, using different immunization routes. after one month f ...	2009	19323012
a replicon trans-packaging system reveals the requirement of nonstructural proteins for the assembly of bovine viral diarrhea virus (bvdv) virion.	a selective trans-packaging system was developed to produce and isolate bovine viral diarrhea virus (bvdv) pseudo-particles with complementing reporter replicons and their packaging proteins expressed in trans with recombinant vaccinia virus. the encapsidation of replicon rns3-5b was dependent not only on the in trans expression of structural proteins c, e(rns), e1 and e2, but also the nonstructural proteins, p7 and contiguous precursor ns2-3-4a. nonstructural p7, ns4b, ns5a or ns5b could be exp ...	2009	19327808
chimeric calicivirus-like particles elicit protective anti-viral cytotoxic responses without adjuvant.	we have analyzed the potential of virus-like particles (vlps) from rabbit hemorrhagic disease virus (rhdv) as a delivery system for foreign t cell epitopes. to accomplish this goal, we generated chimeric rhdv-vlps incorporating a cd8(+) t cell epitope (siinfekl) derived from chicken ovalbumin (ova). the ova epitope was inserted in the capsid protein (vp60) of rhdv at two different locations: 1) the n-terminus, predicted to be facing to the inner core of the vlps, and 2) a novel insertion site pr ...	2009	19327809
emerging biological functions of the vaccinia-related kinase (vrk) family.	the vaccinia-related kinases (vrks) branched off early from the family of casein kinase (ck) i and compose a relatively uncharacterized family of the kinome. the vrks were discovered due to their close sequence relation to the vaccinia virus b1r serine/threonine kinase. they were first described in phosphorylation of transcription factors that led to the discovery of an autoregulatory mechanism between vrk and the tumor suppressor transcription factor p53. the relevance of vrks has broadened rec ...	2009	19337973
evaluation of smallpox vaccines using variola neutralization.	the search for a 'third'-generation smallpox vaccine has resulted in the development and characterization of several vaccine candidates. a significant barrier to acceptance is the absence of challenge models showing induction of correlates of protective immunity against variola virus. in this light, virus neutralization provides one of few experimental methods to show specific 'in vitro' activity of vaccines against variola virus. here, we provide characterization of the ability of a modified va ...	2009	19339477
a single-chain h-2db molecule presenting an influenza virus nucleoprotein epitope shows enhanced ability at stimulating cd8+ t cell responses in vivo.	we have generated a construct encoding a single-chain h-2d(b) mouse mhc class i molecule in which an influenza virus nucleoprotein (np) epitope, amino acid sequence asnenmdam, is fused to mouse beta(2)-microglobulin and the d(b) h chain via flexible linker sequences. this single-chain trimer (sct) was efficiently expressed at the cell surface independently of tap and endogenous beta(2)-microglobulin, and it was recognized directly and efficiently by specific t cells in vitro. a recombinant vacci ...	2009	19342630
vaccination of patients with metastatic renal cancer with modified vaccinia ankara encoding the tumor antigen 5t4 (trovax) given alongside interferon-alpha.	approximately 90% of renal cell tumors overexpress the tumor antigen 5t4. the attenuated strain of vaccinia virus, modified vaccinia ankara, has been engineered to express 5t4 (trovax). we conducted an open-label phase 1/2 trial in which trovax was administered alongside interferon-alpha (ifnalpha) to 11 patients with metastatic renal cell carcinoma. antigen-specific cellular and humoral responses were monitored throughout the study, and clinical responses were assessed by measuring the changes ...	2009	19342962
candidate influenza vaccines based on recombinant modified vaccinia virus ankara.	recombinant modified vaccinia virus ankara (mva) is attractive and promising as a novel viral vector for the expression of foreign genes of interest because it possesses unique properties. in particular, its excellent safety profile and the availability of versatile vector technologies have frequently made mva the vaccinia virus of choice for preclinical and clinical studies. owing to its avirulence and deficiency to productively replicate after in vivo inoculation, mva can be used under biosafe ...	2009	19348560
efficacy of systemically administered oncolytic vaccinia virotherapy for malignant gliomas is enhanced by combination therapy with rapamycin or cyclophosphamide.	the oncolytic effects of a systemically delivered, replicating, double-deleted vaccinia virus has been previously shown for the treatment of many cancers, including colon, ovarian, and others. the purpose of this study was to investigate the oncolytic potential of double-deleted vaccinia virus alone or in combination with rapamycin or cyclophosphamide to treat malignant gliomas in vitro and in vivo.	2009	19351762
a recombinant dna and vaccinia virus prime-boost regimen induces potent long-term t-cell responses to hcv in balb/c mice.	to explore the best prime-boost regimen and evaluate the t-cellular response memory against hcv, we constructed two dna vaccine candidates (pvrc-ce1e2 and paav-ce1e2) and two recombinant viruses (rttv-e1e2 and raav-e1e2) and then assessed the immune response to different prime-boost patterns in balb/c mice. the rttv-e1e2 boosted the immune response to hcv dna vaccine prime significantly, and the inverted terminal repeat sequence harboring dna construct paav-ce1e2 was the best prime agent in this ...	2009	19356609
a multi-valent vaccinia virus-based tuberculosis vaccine molecularly adjuvanted with interleukin-15 induces robust immune responses in mice.	tuberculosis caused by mycobacterium tuberculosis is responsible for nearly two million deaths every year globally. a single licensed vaccine derived from mycobacterium bovis, bacille calmette-guerin (bcg) administered perinatally as a prophylactic vaccine has been in use for over 80 years and confers substantial protection against childhood tuberculous meningitis and miliary tuberculosis. however, the bcg vaccine is virtually ineffective against the adult pulmonary form of tuberculosis that is ...	2009	19356615
the orthopoxvirus 68-kilodalton ankyrin-like protein is essential for dna replication and complete gene expression of modified vaccinia virus ankara in nonpermissive human and murine cells.	modified vaccinia virus ankara (mva) is a highly attenuated and replication-deficient vaccinia virus (vacv) that is being evaluated as replacement smallpox vaccine and candidate viral vector. mva lacks many genes associated with virulence and/or regulation of virus tropism. the 68-kda ankyrin-like protein (68k-ank) is the only ankyrin repeat-containing protein that is encoded by the mva genome and is highly conserved throughout the orthopoxvirus genus. we showed previously that 68k-ank is compos ...	2009	19357172
the expression of the soluble isoform of hflt3 ligand by recombinant vaccinia virus enhances immunogenicity of the vector.	recombinant vaccinia viruses (rvacv) expressing various tumor-associated antigens have been shown to elicit anti-tumor effect in numerous experimental models and clinical trials. we tested the hypotheses that rvacv expressing biologically active fms-like tyrosine kinase 3 ligand (flt3l) would show higher immunogenicity than control viruses expressing only model antigen and that coexpression of flt3l would influence anti-tumor activity of rvacv in the preventive and therapeutic arrangements of th ...	2009	19360312
vaccinia virus infection & temporal analysis of virus gene expression: part 2.	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	19363464
vulvar vaccinia infection after sexual contact with a smallpox vaccinee.	vaccinia (smallpox) vaccine is an effective immunizing agent that brought about global eradication of naturally occurring smallpox, as declared by the world health organization in 1980. the united states ceased generalized smallpox vaccination in 1972 but reinstated it in 2002 for military personnel and selected healthcare workers (first responders who may be investigating possible cases of smallpox or caring for patients in selected hospitals) after the 2001 bioterrorism attacks. since reinstit ...	2009	19365178
vaccinia virus infection & temporal analysis of virus gene expression: part 3.	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	19365326
mva.85a boosting of bcg and an attenuated, phop deficient m. tuberculosis vaccine both show protective efficacy against tuberculosis in rhesus macaques.	continuous high global tuberculosis (tb) mortality rates and variable vaccine efficacy of mycobacterium bovis bacille calmette-guérin (bcg) motivate the search for better vaccine regimes. relevant models are required to downselect the most promising vaccines entering clinical efficacy testing and to identify correlates of protection.	2009	19367339
viral load and clinical disease enhancement associated with a lentivirus cytotoxic t lymphocyte vaccine regimen.	effective dna-based vaccines against lentiviruses will likely induce ctl against conserved viral proteins. equine infectious anemia virus (eiav) infects horses worldwide, and serves as a useful model for lentiviral immune control. although attenuated live eiav vaccines have induced protective immune responses, dna-based vaccines have not. in particular, dna-based vaccines have had limited success in inducing ctl responses against intracellular pathogens in the horse. we hypothesized that priming ...	2009	19368787
disulfide bond formation at the c termini of vaccinia virus a26 and a27 proteins does not require viral redox enzymes and suppresses glycosaminoglycan-mediated cell fusion.	vaccinia virus a26 protein is an envelope protein of the intracellular mature virus (imv) of vaccinia virus. a mutant a26 protein with a truncation of the 74 c-terminal amino acids was expressed in infected cells but failed to be incorporated into imv (w. l. chiu, c. l. lin, m. h. yang, d. l. tzou, and w. chang, j. virol 81:2149-2157, 2007). here, we demonstrate that a27 protein formed a protein complex with the full-length form but not with the truncated form of a26 protein in infected cells as ...	2009	19369327