The vaccinia virus early transcription factor (VETF), in addition to the viral RNA polymerase, is required for efficient transcription of early genes in vitro. VETF is a heterodimeric protein that binds specifically to early gene promoters. In order to localize the VETF DNA binding domain, we have used photoreactive oligonucleotide probes with the sequence of the vaccinia virus growth factor promoter. The probes consisted of double-stranded oligonucleotides incorporating radiolabeled dAMP and 5-bromo-dUMP into sequences of the promoter known to contact VETF. Irradiation of a DNA probe having these nucleotides located upstream of the transcription start site in the presence of VETF resulted in the transfer of label to a polypeptide that comigrated with the small subunit of VETF. The label transfer reaction was shown to occur with the recombinant VETF small subunit in the absence of the large subunit. These results indicate that the small subunit comprises at least part of the VETF DNA binding ...
Using a reverse genetic approach, we have demonstrated that the product of the B5R open reading frame (ORF), which has homology with members of the family of complement control proteins, is a membrane glycoprotein present in the extracellular enveloped (EEV) form of vaccinia virus but absent from the intracellular naked (INV) form. An antibody (C-B5R) raised to a 15-amino-acid peptide from the translated B5R ORF reacted with a 42-kDa protein (gp42) found in vaccinia virus-infected cells and cesium chloride-banded EEV but not INV. Under nonreducing conditions, an 85-kDa component, possibly representing a hetero- or homodimeric form of gp42, was detected by both immunoprecipitation and Western immunoblot analysis. Metabolic labeling with [3H]glucosamine and [3H]palmitate revealed that the B5R product is glycosylated and acylated. The C-terminal transmembrane domain of the protein was identified by constructing a recombinant vaccinia virus that overexpressed a truncated, secreted form of the B5R ...
GL-ONC1, an oncolytic vaccinia virus, has shown the ability to preferentially locate, colonize and destroy tumor cells in more than 40 different human tumors. A First-in-Man, Phase I clinical study focusing on the safety and tolerability of GL-ONC1 intravenously administered to patients with a variety of advanced solid tumor entities has shown that GL-ONC1 is well-tolerated at therapeutic dose levels, with documented evidence of antitumor activity. Preclinical studies have further shown synergistic effects with the use of chemotherapy (Cisplatin) and viral therapy with GL-ONC, as well as favorable results when cancer cells are irradiated and then treated with GL-ONC1 in animal models. This Phase I study seeks to evaluate the safety, tolerability and early signs of efficacy of GL-ONC1 administered intravenously in combination with standard of care (SOC) radiation therapy (RT) and cisplatin (CDDP)in patients with locoregionally advanced head and neck cancer. Patients will be individually assessed ...
TY - JOUR. T1 - Use of apathogenic vaccinia virus MVA expressing EHV-1 gC as basis of a combined recombinant MVA/DNA vaccination scheme. AU - Huemer, Hartwig P.. AU - Strobl, Birgit. AU - Nowotny, Norbert. PY - 2000/2/4. Y1 - 2000/2/4. N2 - The nonreplicating chicken adapted vaccinia virus strain MVA was used in a combined vaccine scheme. Using the equine herpesvirus type 1 (EHV-1) encoded complement-receptor glycoprotein C as antigen, only poor antibody response was induced by exclusive vaccination with DNA plasmids. The administration of recombinant MVA followed by plasmid immunization elicited both humoral and cellular immune responses in hamster comparable to EHV-1 full virus vaccines. Our results indicate that recombinant constructs based on MVA represent a safe and efficient way to overcome problems of poor immunogenicity of certain antigens upon intramuscular DNA vaccination, thus replacing sophisticated adjuvants or application methods, which are not readily applicable in routine ...
61840DNAVaccinia virus 1tttttattat ttgtacgatg tccaggataa catttttacg gataaataaa tatgaaggtg 60gagagcgtga cgttcctgac attgttggga ataggatgcg ttctatcatg ctgtactatt 120ccgtcacgac ccattaatat gaaatttaag aatagtgtgg agactgatgc taatgctaat 180tacaacatag gagacactat agaatatcta tgtctacctg gatacagaaa gcaaaaaatg 240ggacctatat atgctaaatg tacaggtact ggatggacac tctttaatca atgtattaaa 300cggagatgcc catcgcctcg agatatcgat aatggccaac ttgatattgg tggagtagac 360tttggctcta gtataacgta ctcttgtaat agcggatatc atttgatcgg tgaatctaaa 420tcgtattgtg aattaggatc tactggatct atggtatgga atcccgaggc acctatttgt 480gaatctgtta aatgccaatc ccctccatct atatccaacg gaagacataa cggatacgag 540gatttttata ccgatgggag cgttgtaact tatagttgca atagtggata ttcgttgatt 600ggtaactctg gtgtcctgtg ttcaggagga gaatggtccg atccacccac gtgtcagatt 660gttaaatgtc cacatcctac aatatcaaac ggatacttgt ctagcgggtt taaaagatca 720tactcataca acgacaatgt agactttaag tgcaagtacg gatataaact atctggttcc 780tcatcatcta cttgctctcc aggaaataca tggaagccgg aacttccaaa atgtgtacgc 8402244PRTVaccinia virus ...
The mechanism by which cyclosporin A (CsA) inhibits vaccinia virus (VV) replication is still unclear. The present study addresses the question of whether CsA-binding proteins named cyclophilins (Cyps) are involved in the anti-VV activity of CsA. Six CsA analogues were analysed, and their affinity for Cyps in VV-infected BSC-40 cells and their potency as inhibitors of VV replication were evaluated. It was demonstrated that analogues with strong Cyp-binding activity, such as CsC, CsG and [MeAla6]CsA, also exhibit a strong antiviral effect. In contrast, drugs with low ([MeBm2t1]CsA and CsH) or no ([MeLeu11]CsA) affinity for Cyps show poor or no antiviral activity. The data obtained suggest a correlation between the ability of CsA to block VV replication and Cyp binding activity, and indicate the involvement of Cyps in the VV replicative cycle. They also suggest that the anti-VV action of CsA may occur by a pathway distinct from that involved in the immunosuppressive effect of the drug.
A major obstacle in designing effective vaccines is our limited knowledge of the mechanisms involved in eliciting a protective cell-mediated immune response. In recent years, research has focused on the development of recombinant vaccines, in which antigenic peptides derived from a specific pathogen are delivered to the cells via live vectors. For a vaccine to be effective in an out-bred population it must generate as many antigenic determinants as possible. One method that can be used to generate multiple peptide determinants is to express two or more recombinant proteins from a single live vaccine vector. To this end, we developed a recombinant vaccinia virus system that expresses two full-length influenza virus proteins; nucleoprotein (NP) and acidic polymerase (PA). In addition to the NP and PA proteins, our expression system is designed to produce yellow and red fluorescent proteins, which allow us to monitor, in a quantitative manner, recombinant protein expression both in vitro and in ...
Vaccinia virus (VV) morphogenesis commences with the formation of lipid crescents that grow into spherical immature virus (IV) and then infectious intracellular mature virus (IMV) particles. Early studies proposed that the lipid crescents were synthesized de novo and matured into IMV particles that contained a single lipid bilayer (S. Dales and E. H. Mosbach, Virology 35:564-583, 1968), but a more recent study reported that the lipid crescent was derived from membranes of the intermediate compartment (IC) and contained a double lipid bilayer (B. Sodiek et al., J. Cell Biol. 121:521-541, 1993). In the present study, we used high-resolution electron microscopy to reinvestigate the structures of the lipid crescents, IV, and IMV particles in order to determine if they contain one or two membranes. Examination of thin sections of Epon-embedded, VV-infected cells by use of a high-angular-tilt series of single sections, serial-section analysis, and high-resolution digital-image analysis detected only a single,
Immunogenic cell death (ICD) is associated with the emission of so-called damage-associated molecular patterns (DAMPs) which trigger the immune response against dead-cell associated antigens. The secretion of the DAMP, adenosine triphosphate (ATP) has been shown to be autophagy-dependent. Here, we demonstrate that Modified Vaccinia virus Ankara (MVA), a highly attenuated strain of vaccinia virus, induces both cell death and autophagy in murine bone marrow-derived dendritic cells (BMDCs), which in turn confer the (cross-)priming of OVA-specific cytotoxic T cells (OT-I cells). Additionally, we show that MVA infection leads to increased extracellular ATP (eATP) as well as intracellular ATP (iATP) levels, with the latter being influenced by the autophagy. Furthermore, we show that the increased eATP supports the proliferation of OT-I cells and inhibition of the P2RX7 receptors results in an abrogation of the proliferation. These data reveal novel mechanisms on how MVA enhances adaptive immunity in ...
One of the great success stories of modern medicine is the eradication of smallpox virus that was declared in 1980 after a long vaccination campaign with vaccinia virus. A risk remains today of the resurgence of smallpox virus from a frozen source such as the melting of permafrost [1]. Another risk is the spread of an orthopoxvirus from an animal reservoir to the human population. The present work focuses on vaccinia virus, which is a safe model system to study poxviruses. The high-resolution structure that has been obtained of components of the vaccinia virus DNA replication machinery will facilitate the development of drugs and help to understand orthopoxvirus drug resistance.. The crystal structure determination of vaccinia virus polymerase was challenging due to the radiation sensitivity of the long needle-like DNA polymerase crystals obtained from low amounts of protein produced in insect cells. The use of the helical scan capability at the ESRF with a simultaneous rotation and translation ...
An inducible, mutant virus, designated vvtetO:I7L/G1L, was used to study the morphogenic proteolysis step of the vaccinia virus life cycle. The vvtetO:I7L/G1L controlled the expression of two genes, I7L, a cysteine proteinase, and G1L, a putative metalloproteinase. These proteins are involved in the maturation of viral core proteins, p4a, p4b, and p25K, to form infectious virions. DNA extraction and genomic sequencing verified the correct insertion of the tetracycline operators. The multiplicity of infection (MOI) was optimized, and a MOI of 0.5 was best, with a 99.25% reduction in viral plaque formation compared to the wild type vaccinia virus. A growth curve over 12 hours was done and the vvtetO:I7L/G1L in the "on" state closely followed the growth kinetics of the wild type vaccinia virus and the vvtetO:I7L/G1L in the "off" state had significantly lower viral titers throughout the last 6 hours of the cycle. Viral core protein processing in the "on" and "off" states, and in rescue experiments ...
Two chimpanzees were vaccinated intramuscularly against malaria using plasmid DNA expressing the pre-erythrocytic antigens thrombospondin related adhesion protein (PfTRAP) and liver stage specific antigen-1 (PfLSA-1) of Plasmodium falciparum together with GM-CSF protein. A recombinant modified vaccinia virus Ankara (MVA) expressing PfTRAP was injected intramuscularly 6 weeks later to boost the immune response. This sequence of antigen delivery induced a specific and long-lasting T cell and antibody response to PfTRAP as detected by ELISPOT assay and ELISA. Antibody responses were detected after four DNA injections, and were boosted by injection of recombinant MVA expressing PfTRAP. Interferon-gamma secreting antigen-specific T cells were detected in both animals, but only after boosting with recombinant MVA. By screening a panel of PfTRAP-derived peptides, an epitope was identified that was recognized by cytotoxic T lymphocytes in one of the chimpanzees studied. T cells specific for this epitope were
Vaccinia virus infected cell. Immunofluorescence deconvolution micrograph of a cell infected with vaccinia virus particles. The nucleus of the host cell is blue. Areas of virus assembly within the cell are pink. Actin protein filaments, which make up part of the cytoskeleton, are green. The cytoskeleton maintains the cells shape, allows some cellular mobility and is involved in intracellular transport. Vaccinia causes cowpox, a disease of cattle and humans, which produces skin lesions. - Stock Image C002/5930
This study evaluated vaccinia-vectored vaccines expressing glycoproteins gB, gC, or gD of pseudorabies virus (PRV) in pigs. The vaccines are based on an attenuated vaccinia virus strain, NYVAC, which has reduced virulence and replicative capacity for certain species, including swine. The recombinant vaccinia vaccines were unable to prevent replication of virulent pseudorabies virus or latency but they were able to decrease the amount of virus shed after challenge and decrease clinical signs. In particular, pigs vaccinated with the recombinants expressing either gB or gD were protected at a level comparable to an inactivated PRV virus that was given for comparison. No lesions or clinical signs were seen following vaccination in these studies and no seronegative pigs in contact with vaccinia-vaccinated pigs ever seroconverted. No significant increase in protection occurred by giving recombinants expressing multiple glycoproteins and there was no virus neutralizing antibody response or protection induced
Activation of T cells requires at least two signals: an antigen-specific signal delivered through the T-cell receptor and a costimulatory signal mediated through molecules designated B7-1 and B7-2. Previous studies have shown that introduction of B7-1 and B7-2 into tumors using retroviral vectors has led to enhanced antitumor effects. A limiting factor for potential clinical applications using this approach is the low efficiency of infection of retroviral vectors and consequent manipulations of infected cells. Vaccinia virus thus represents an alternative vector for B7 gene expression in tumor cells. In this report we describe the construction and characterization of recombinant vaccinia viruses containing the murine B7-1 and B7-2 genes (designated rV-B7-1 and rV-B7-2). Infection of BSC-1 cells with these constructs results in rapid and efficient cell surface expression of both B7-1 and B7-2 (,97% of cells at 4 h). Infection of murine carcinoma cells with low multiplicity of infection of ...
If we mapped out the family tree of poxviruses, then vaccinia virus (the causative agent of cowpox) and variola virus (the causative agent of smallpox) would probably be sisters. Or at the very least, cousins. This close heritage allows the relatively benign vaccinia virus to confer variola virus-protective immune responses in vaccinated individuals. A safely…
T cell-mediated cytotoxicity may play an important role in controlling infection by human immunodeficiency virus (HIV). In order to study the ability of rationally designed antigens to induce cytolytic T lymphocytes (CTLs) we replaced stretches of 30 to 50 amino acids at the p17-MA/p24-CA cleavage site, within the p24-CA moiety and within the p6-LI portion of the HIV type 1 p55gag precursor by the third variable domain (V3) of the external glycoprotein gp120. This site is known to be a target for CTL attack in mice and humans. The chimeric antigens were recombined into highly attenuated vaccinia viruses in order to investigate class I major histocompatibility complex (MHC)-restricted presentation of antigenic V3 peptides. Immunoprecipitation and Western blot analysis of the group-specific antigen (p55gag)/V3 chimeric proteins demonstrated significant differences in the accessibility of the V3 domain for a monoclonal antibody or polyclonal V3-specific antisera, depending on the position of the V3 ...
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NYVAC Pf7 vaccine: a multiantigen and multistage vaccine candidate for malaria; NYVAC-Pf7 is a highly attenuated vaccinia virus with 7 P. falciparum genes inserted into its genome
Vaccinia Virus G1 Protein, a Predicted Metalloprotease, Is Essential for Morphogenesis of Infectious Virions but Not for Cleavage of Major Core Proteins: Genes
Our group is considering using a vaccinia virus for expression of cDNAs in tissue culture cells. 1. Is such a system commercially available? 2. Is there anyone out there who is familiar with this system who can comment on its ease of use and success? 3. Are there safety issue involved with using vaccinia virus (Level 2 biosafety?). Thanks, Karen Kedzie Allergan Pharmaceuticals, Inc. Irvine CA 92715 ...
Secondary effector T-cell populations generated by cross-priming with heterologous influenza A viruses operate only in H-2K or H-2D compatible situations, when assayed on SV40-transformed target cells infected with a range of influenza A viruses. The H2-Kb allele is associated with a total failure in the generation of influenza-immune cytotoxic T cells, though this is not seen for the primary response to vaccinia virus. In both influenza and vaccinia development of effector T cells operating at H-2Db is greatly depressed in B10.A(2R) (kkkddb) and B10.A(4R) (kkbbbb), but not in B10 (bbbbbb), mice. However, there is no defect in viral antigen expression at either H-2Kk or H-2Db in B10.A(2R) target cells. This apparently reflects some inadequacy in the stimulator environment, as (A/J X B6) F1 T cells can be induced to respond at H-2Db when exposed to vaccinia virus in an irradiated B6 but not in a B10.A(4R) recipient. The present report, together with the accompanying paper by Zinkernagel and ...
The IL-1 superfamily of cytokines and receptors has been studied extensively. However, the specific roles of IL-1 elements in host immunity to cutaneous viral infection remain elusive. In this study, we applied vaccinia virus (VACV) by scarification to IL-1R1 knockout mice (IL-1R1−/−) and found that these mice developed markedly larger lesions with higher viral genome copies in skin than did wild-type mice. The phenotype of infected IL-1R1−/− mice was similar to eczema vaccinatum, a severe side effect of VACV vaccination that may develop in humans with atopic dermatitis. Interestingly, the impaired cutaneous response of IL-1R1−/− mice did not reflect a systemic immune deficiency, because immunized IL-1R1−/− mice survived subsequent lethal VACV intranasal challenge, or defects of T cell activation or T cell homing to the site of inoculation. Histologic evaluation revealed that VACV infection and replication after scarification were limited to the epidermal layer of wild-type mice, ...
ID DNLI_VACCW Reviewed; 552 AA. AC P16272; Q76ZM8; DT 01-AUG-1990, integrated into UniProtKB/Swiss-Prot. DT 01-AUG-1990, sequence version 1. DT 25-OCT-2017, entry version 93. DE RecName: Full=DNA ligase; DE EC=6.5.1.1 {ECO:0000255,PROSITE-ProRule:PRU10135}; DE AltName: Full=Polydeoxyribonucleotide synthase [ATP]; GN Name=LIG; OrderedLocusNames=VACWR176; ORFNames=A50R; OS Vaccinia virus (strain Western Reserve) (VACV) (Vaccinia virus (strain OS WR)). OC Viruses; dsDNA viruses, no RNA stage; Poxviridae; Chordopoxvirinae; OC Orthopoxvirus; Vaccinia virus. OX NCBI_TaxID=10254; OH NCBI_TaxID=9913; Bos taurus (Bovine). RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=2045793; DOI=10.1099/0022-1317-72-6-1349; RA Smith G.L., Chan Y.S., Howard S.T.; RT "Nucleotide sequence of 42 kbp of vaccinia virus strain WR from near RT the right inverted terminal repeat."; RL J. Gen. Virol. 72:1349-1376(1991). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=2555782; DOI=10.1093/nar/17.22.9051; RA Smith ...
Recombinant poxviruses expressing immuno-modulatory molecules together with specific antigens might represent powerful vaccines for cancer immunotherapy. Recently, we and others have demonstrated, in vitro and in clinical trials, that co-expression of costimulatory molecules (CD80 and CD86) could increase the immunogenic capacity of a recombinant Vaccinia virus (rVV) also encoding different tumor associated antigens. In order to further investigate the capacity of these vectors to provide ligands for different co-stimulatory pathways relevant in the generation of CD8+ T cell responses, we designed a recombinant virus expressing CD40 ligand (CD154rVV). This co-receptor, expressed on activated CD4+ T cells, upon binding CD40 expressed on antigen presenting cells (APC) has been reported to increase their antigen presentation and immunomodulatory capacities. To investigate the potency of CD154rVV in CTL generation, different types of infection were performed in cultures containing APC and CD8+ T ...
The present invention provides an attenuated virus, which is derived from Modified Vaccinia Ankara virus and characterized by the loss of its capability to reproductively replicate in human cell lines. It further describes recombinant viruses derived from this virus and the use of the virus, or its recombinants, as a medicament or vaccine. A method is provided for inducing an immune response in individuals who may be immune-compromised, receiving antiviral therapy, or have a pre-existing immunity to the vaccine virus. In addition, a method is provided for the administration of a therapeutically effective amount of the virus, or its recombinants, in a vaccinia virus prime/vaccinia virus boost innoculation regimen.
A factor, present in transcriptionally active extracts prepared from purified vaccinia virus particles, binds to vaccinia early promoter sequences. The specificity of binding was demonstrated by electrophoretic mobility shift assays using the 5-terminal segments of two early genes and related and unrelated competitor DNA fragments. DNase I "footprint" analysis indicated that the factor formed a complex with promoter regions of both genes and protected sequences of 10-15 nucleotides centered 21-24 nucleotides upstream of the RNA start sites. The lack of protection of a late regulatory sequence and of an early promoter with transcriptionally inactivating single-nucleotide substitutions suggested that the protein is an early transcription factor. When subjected to glycerol gradient centrifugation, the DNA-binding factor was resolved from RNA polymerase and sedimented as a 7.5S species with an estimated molecular weight of 130,000. ...
Athymic nude mice recover from an infection with recombinant vaccinia virus (VV) encoding murine interleukin 2 (IL-2), but treatment with a mAb to IL-2 accentuated infection. Administration of a mAb against interferon gamma (IFN-gamma) to mice infected with the IL-2-encoding virus completely prevented the IL-2-induced mechanisms of recovery. Both asialo-GM1+ (NK) and asialo-GM1- (non-NK) cells were participants in the IFN-gamma-mediated recovery of nude mice from infection with the IL-2-encoding VV recombinant. Depletion of asialo-GM1+ cells exacerbated infection, though not as much as anti-IFN-gamma mAb. In vitro, both asialo-GM1+ and asialo-GM1- nude mouse splenocytes produced IFN-gamma in response to IL-2. ...
A vaccine against human immunodeficiency virus (HIV) is still awaited. Although the correlates of protection remain elusive, it is likely that CD8+ T cells play an important role in the control of this infection. To firmly establish the importance of these cells in protective immunity, a means of efficient elicitation of CD8+ T cell responses in the absence of antibody is needed and, when available, might represent a crucial step towards a protective vaccine. Here, a novel vaccine candidate was constructed as a multi-cytotoxic T lymphocyte (CTL) epitope gene delivered and expressed using modified vaccinia virus Ankara (MVA). The immunogen consists of 20 human, one murine and three rhesus macaque epitopes. The non-human epitopes were included so that the vaccine can be tested for immunogenicity and optimal vaccination doses, routes and regimes in experimental animals. Mice were immunized intravenously (i.v.) or intramuscularly (i.m.) using a single dose of 10(6) p.f.u. of the recombinant MVA and the
The worldwide HIV/AIDS epidemic may only be controlled through a safe and effective vaccine that will prevent HIV infection. DNA vaccines are inexpensive to construct, easily produced in large quantities, and stable for long periods of time. Recombinant modified vaccinia Ankara vaccines have been shown to be safe in humans, and immunogenicity after administration of both vaccines has been encouraging. When used together, a more robust immunologic response was associated with DNA HIV vaccine administration followed by modified vaccinia vaccine administration, compared to using either DNA or vaccinia vaccine alone. This study will evaluate the safety and immunogenicity of an experimental DNA HIV vaccine prime, pGA/JS7, followed by a similarly structured modified vaccinia boost, MVA/HIV62, in HIV uninfected adults. Participants in this study will be recruited only in the United States.. This study will be divided into 2 parts. Each participant will be involved with their part of study for 1 year. ...
The safety of attenuated poxviruses in HIV-1-infected individuals is an important consideration in their application as vaccine vectors, first, because new HIV-1 infections may occur in vaccine trials involving persons at high risk of infection and secondly, therapeutic vaccinations are a potential means to enhance virus-specific immune responses once infection has occurred. We administered a candidate modified vaccinia virus Ankara-vectored HIV-1 vaccine, MVA.HIVA, by intradermal injection to 16 chronically infected adults during highly active antiretroviral therapy. Vaccinations were well tolerated and there were no serious adverse events. No breakthrough viraemia occurred after immunisations or throughout follow-up. These data confirm the safety of MVA.HIVA in HIV-1-infected individuals and provide support for further evaluation of MVA-vectored vaccines in prophylactic and therapeutic immunisation strategies.
Envelope protein which probably plays a role in virus entry into the host cell. Is probably involved in the virus attachment to the host cell surface and associates with the entry/fusion complex (EFC). Needed for fusion and penetration of the virus core into host cell.
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Suramin is a competitive inhibitor of heparin binding to many proteins, including viral envelope proteins, protein tyrosine phosphatases, and fibroblast growth factors (FGFs). It has been clinically evaluated as a potential therapeutic in treatment of cancers caused by unregulated angiogenesis, triggered by FGFs. Although it has shown clinical promise in treatment of several cancers, suramin has many undesirable side effects. There is currently no experimental structure that reveals the molecular interactions responsible for suramin inhibition of heparin binding, which could be of potential use in structure-assisted design of improved analogues of suramin. We report the structure of suramin, in complex with the heparin-binding site of vaccinia virus complement control protein (VCP), which interacts with heparin in a geometrically similar manner to many FGFs. The larger than anticipated flexibility of suramin manifested in this structure, and other details of VCP-suramin interactions, might ...
INDEFINITE BACKORDER*** Epidermal growth factor receptor (EGFR) is a receptor for EGF and for various members of the EGF family such as TGF-alpha, amphiregulin, betacellulin, heparin-binding EGF-like growth factor, GP30 and vaccinia virus growth factor. EGFR is involved in the control of cell growth and differentation. Binding of EGF to the receptor leads to dimerization, internalization of the EGF-receptor complex, induction of the tyrosine kinase activity, stimulation of cell DNA synthesis and cell proliferation. EGFRvIII has an 801-bp in-frame deletion resulting in a shorter extracellular domain (aa 6-273 are deleted) with generation of a glycine residue at the fusion point. EGFRvIII is tumor specific and is not expressed in normal human tissues. Defects in EGFR are associated with lung cancer.. ...
EGFR a receptor tyrosine kinase. This is a receptor for epidermal growth factor (EGF) and related growth factors including TGF-alpha, amphiregulin, betacellulin, heparin-binding EGF-like growth factor, GP30, and vaccinia virus growth factor. EGFR is involved in the control of cell growth and differentiation. It is a single-pass transmembrane tyrosine kinase. Ligand binding to this receptor results in receptor dimerization, autophosphorylation (in trans), activation of various downstream signaling molecules and lysosomal degradation. It can be phosphorylated and activated by Src. Activated EGFR binds the SH2 domain of phospholipase C-gamma (PLC-gamma), activating PLC-gamma-mediated downstream signaling. Phosphorylated EGFR binds Cbl, leading to its ubiquitination and degradation. Grb2 and SHC bind to phospho-EGFR and are involved in the activation of MAP kinase signaling pathways. Phosphorylation on Ser and Thr residues is thought to represent a mechanism for attenuation of EGFR kinase activity. ...
ID PCP1 preliminary; circular DNA; SYN; 3600 BP. XX AC S62800; ATCC37351; XX DT 01-JUL-1993 (Rel. 7, Created) DT 01-JUL-1995 (Rel. 12, Last updated, Version 1) XX DE Vertebrate/E.coli plasmid vector pCP1 - incomplete. XX KW cloning vector. XX OS Cloning vector OC Artificial sequences; Cloning vehicles. XX RN [1] RC plasmid from pUC9 & vaccinia virus 7.5kDa gene RC pCP1 from pCAT & plasmid RC pMM24 from pMM23 & SV40 72-bp repeats RA Cochran M.A., Mackett M., Moss B.; RT "Eukaryotic transient expression system dependent on transcription RT factors and regulatory DNA sequences of vaccinia virus"; RL Proc. Natl. Acad. Sci. U.S.A. 82:19-23(1985). XX RN [2] RC plasmid from pBR328 RC pGS8 from plasmid & vaccinia virus TK gene RC pMM1 from pUC9 & vaccinia virus TK gene RC pMM2 from pUC9 & vaccinia virus TK gene RC pMM3 from pMM1 & pMM2 RC pMM4 from pMM3 RC pMM5 from pMM4 RC pGS15 from pUC9 & pAG4 RC pGS19 from pGS15 & linker RC pGS20, pGS21 from pGS19 & pGS8 RC [pGS30 from cat gene] RC pCAT from pBR328 ...
In order to produce infectious virus progeny, vaccinia virus (VV) undergoes morphogenic proteolysis to regulate the structural rearrangements of virus particles. Several of the major structural precursor proteins of VV are cleaved at a conserved Ala-Gly-X (where X is any amino acid) motif by the VV I7L core protein proteinase at a step, which is necessary for formation of mature virus particles. VV A12L encodes a 25kDa core protein, which is cleaved at an AG/A site, yielding a 17kDa cleavage product. Both A12L precursor and the cleavage product are localized to mature virions. The open reading frame (ORF) of A12L contains two more AG/X (AG/K) sites, however, cleavage at these sites has not been analyzed. Therefore, the aim of this study is to characterize the in vivo processing of A12L proteolysis and elucidate the biological function of A12L. The result of these studies would provide more details on the regulation and participation of VV proteolysis during the morphogenic transitions. ...
Recombinant virus vectors represent a promising strategy for vaccine research. Among available viral vectors, members of the Poxviridae family-especi
Vijaya, S and Vasu, * and Gowda, Arjuna KV and Narasimhamurthy, T and Rathore, RS (2011) 4-(4-Chlorophenyl)-N-[(E)-4-(dimethylamino)benzylidene]-1,3-thiazol-2- amine. In: Acta Crystallographica Section E, 67 (Part 8). O2115-U1228. Vijaya, S (1998) The genetics of Mycobacterium tuberculosis. In: Journal of Genetics, 77 (2-3). pp. 123-128. Wolffe, Elizabeth J and Vijaya, S and Moss, Bernard (1995) A Myristylated Membrane Protein Encoded by the Vaccinia Virus L1R Open Reading Frame Is the Target of Potent Neutralizing Monoclonal Antibodies. In: Virology, 211 (1). pp. 53-63. Kalyani, P and Vijaya, S and Ramasarma, T (1992) Characterization of oxygen free radicals generated during vanadate-stimulated NADH oxidation. In: Molecular and Cellular Biochemistry, 111 (1-2). pp. 33-40. Ramasarma, T and Rasheed, BK and Vijaya, S and Puranam, RS and Shivaswamy, V and Gaikwad, AS and Kurup, CK (1992) Functions Of Cytochrome-C In Regulation Of Electron-Transfer And Protein Folding. In: Indian Journal of ...
Tipapkinogene sovacivec is a vaccine comprising an attenuated vaccinia virus (MVA) encoding human papillomavirus 16 (HPV 16) proteins L1, L2, E6 and E7, as well
Free resource for searching and exporting immune epitopes. Includes more than 95% of all published infectious disease, allergy, autoimmune, and transplant epitope data.
Vaccinia virus (VACV) protein N1 is an intracellular virulence factor and belongs to a family of VACV B-cell lymphoma (Bcl)-2-like proteins whose members inhibit apoptosis or activation of pro-inflammatory transcription factors, such as interferon (I
Ertl, Hildegund; Gerike, Rainer und Koszinowski, Ulrich H. (1977): Virus-Specific T-Cell Sensitization. Requirements for vaccinia virus specific T cell sensitization in vivo. In: Journal of immunogenetics, Vol. 4: S. 515-522 ...
vaccinia virus nicking-joining enzyme: virus-specific, DNA-dependent & does not require ATP; possesses both endonuclease & ligase activities
Two-hybrid screens generate significant numbers of false positives, which are not reproducible in a duplicate screen. This random generation of histidine-positive colonies can result from rearrangements and deletions of the DNA-binding domain plasmid, recombinational events between the DNA-binding and activation domain plasmids, and genomic rearrangements of the host strain. To enable the rapid detection of reproducible two-hybrid interactions, we constructed the vaccinia virus array with four separate yeast transformants, corresponding to each activation domain hybrid protein. Thus, the array consisted of 1,064 colonies of these transformants, plus controls, which required three microtiter-sized plates of 384-colony capacity. The array of activation domain transformants was screened against each viral DNA-binding domain transformant. Growth on plates lacking histidine, selective for expression of the GAL1-HIS3 reporter gene, was observed either as a cluster of sister colonies, or as dispersed ...
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Poxviruses encode proteins that suppress host immune responses, including secreted decoy receptors for pro-inflammatory cytokines such as interleukin-1 (IL-1) and the vaccinia virus proteins A46R and A52R that inhibit intracellular signaling by members of the IL-1 receptor (IL-1R) and Toll-like receptor (TLR) family. In vivo, the TLRs mediate the innate immune response by serving as pathogen recognition receptors, whose oligomerized intracellular Toll/IL-1 receptor (TIR) domains can initiate innate immune signaling. A family of TIR domain-containing adapter molecules transduces signals from engaged receptors that ultimately activate NF-kappaB and/or interferon regulatory factor 3 (IRF3) to induce pro-inflammatory cytokines. Data base searches detected a significant similarity between the N1L protein of vaccinia virus and A52R, a poxvirus inhibitor of TIR signaling. Compared with other poxvirus virulence factors, the poxvirus N1L protein strongly affects virulence in vivo; however, the precise target of