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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sequencing and computer analysis of the variola major virus strain India-1967 (VAR-IND) genome segment (53,018 bp) from the right terminal region have been carried out. Fifty nine potential open reading frames (ORFs) of over 60 amino acid residues have been identified. Structure-function organization of VAR-IND DNA segment under study was compared with the previously reported sequences from the analogous genomic regions of vaccinia virus strains Copenhagen (VAC-COP) and Western Reserve (VAC-WR) and variola virus strain Harvey (VAR-HAR). Multiple distinctions in the genetic map of VAR-IND from VAC-COP and VAC-WR have been revealed along with the high similarity to the corresponding VAR-HAR segment. Possible functions of the predicted viral proteins and the effect of their differences on the features of orthopoxviruses are discussed.
Mol Biol (Mosk)
PMID:[Study of the structure-function organization of the variola virus genome. IV. Sequencing and analysis of the nucleotide sequence of the right terminus of the India-1967 strain genome]. 747 44

The production and the role of POLADS in cells infected with vaccinia virus (VV) was studied in doubly infected HeLa and L cells. In cells first infected with VV followed by superinfection with UV-irradiated virus (VVuv), referred to as VV + VVuv, the course of viral polypeptide synthesis was not significantly altered. However, if cells were first infected with VVuv, followed by superinfection with VV, referred to as VVuv + VV, both host and viral polypeptide synthesis was compromised. Labeling of such infected cells with 3H-adenosine revealed that infection with VVuv or VVuv + VV, caused an amplification of incorporation of label both in the large and small size class RNAs compared to RNAs obtained from a normal infection. On the other hand, labeling of cells with 3H-adenosine which were infected with VV + VVuv, caused no significant change in the labeling pattern of large and small size class RNAs compared to labeled RNAs from normal infection. The large size class RNAs isolated from infection with VVuv or VVuv + VV, were translated in the reticulocyte lysate cell-free system much more productively compared to the same size RNAs obtained from normal infection. When these large size class RNAs were added together with HeLa cell mRNAs to the cell-free translational system, competition between the two types of mRNAs ensued. The small size class RNAs (POLADS) isolated from infection with VVuv or VVuv + VV, had little translational activity, but when added together with HeLa cell mRNAs, caused a striking inhibition of HeLa cell mRNA translation which was more pronounced than the inhibition caused by the small size class RNAs obtained from normal infections. POLADS obtained from infection with VV or VV + VVuv inhibited HeLa cell protein synthesis to the same extent and were about two times less active than the POLADS obtained from infection with VVuv or VVuv + VV. These results demonstrate that if cells are first infected with normal virus, the superinfecting UV-irradiated virus has little or no effect on the course of VV replication, suggesting that the production of POLADS under these conditions is regulated. However, when cells are first infected with VVuv, POLADS production is amplified to an "abnormal" level, thus, both viral polypeptide synthesis and replication of the superinfecting VV is compromised resulting in lower yields of virus.
Cell Mol Biol Res 1993
PMID:Amplification of polyadenylated nontranslated small RNA sequences (POLADS) during superinfection correlates with the inhibition of viral and cellular protein synthesis. 750 90

The selective inhibition of host-cell protein synthesis was studied in cells infected with vaccinia virus (VV) under aberrant conditions of transcription. Previous studies in our laboratory have correlated this selective inhibition with a class of short polyadenylated virus-directed RNAs (POLADS) which are synthesized in VV-infected cells during the early phase of transcription. Moreover, it was shown that infection of HeLa cells with UV-irradiated VV or infection in the presence of actinomycin D (ACD) amplifies the synthesis of POLADS compared to the amount produced in cells infected under normal conditions. To further study the role of POLADS in shut-off, we utilized a temperature sensitive mutant of VV which induces only marginal host shut-off at the restrictive temperature. POLADS were isolated from cells infected with either unirradiated or UV-irradiated VV ts mutant at the permissive and restrictive temperatures and their inhibitory activity on translation in vitro was assayed. The study yields further evidence associating excess of POLADS with greater inhibitory potential and supports the speculation that the increased production of POLADS is correlated with the inhibition of translation of both host-cell and viral polypeptides, albeit to different degrees. The results also demonstrate that a lack of POLADS accumulation is related to a corresponding reduction of shut-off.
Cell Mol Biol Res 1993
PMID:Role of polyadenylated RNA sequences (POLADS) in vaccinia virus infection: correlation between accumulation of POLADS and extent of shut-off in infected cells. 751 42

Vaccinia virus mRNA capping enzyme is a multifunctional protein with RNA triphosphatase, RNA guanylyltransferase, RNA (guanine-7) methyltransferase, and transcription termination factor activities. The protein is a heterodimer of 95- and 33-kDa subunits encoded by the vaccinia virus D1 and D12 genes, respectively. The capping reaction entails transfer of GMP from GTP to the 5'-diphosphate end of mRNA via a covalent enzyme-(lysyl-GMP) intermediate. The active site is situated at Lys-260 of the D1 subunit within a sequence element, KxDG (motif I), that is conserved in the capping enzymes from yeasts and other DNA viruses and at the active sites of covalent adenylylation of RNA and DNA ligases. Four additional sequence motifs (II to V) are conserved in the same order and with similar spacing among the capping enzymes and several ATP-dependent ligases. The relevance of these common sequence elements to the RNA capping reaction was addressed by mutational analysis of the vaccinia virus D1 protein. Nine alanine substitution mutations were targeted to motifs II to V. Histidine-tagged versions of the mutated D1 polypeptide were coexpressed in bacteria with the D12 subunit, and the His-tagged heterodimers were purified by Ni affinity and phosphocellulose chromatography steps. Whereas each of the mutated enzymes retained triphosphatase, methyltransferase, and termination factor activities, six of nine mutant enzymes were defective in some aspect of transguanylylation. Individual mutations in motifs III, IV, and V had distinctive effects on the affinity of enzyme for GTP, the rate of covalent catalysis (EpG formation), or the transfer of GMP from enzyme to RNA. These results are concordant with mutational studies of yeast RNA capping enzyme and suggest a conserved structural basis for covalent nucleotidyl transfer.
Mol Cell Biol 1995 Nov
PMID:Mutational analysis of mRNA capping enzyme identifies amino acids involved in GTP binding, enzyme-guanylate formation, and GMP transfer to RNA. 756 75

In an attempt to determine whether immunization of healthy HIV-1 seronegative individuals with a soluble gp160 candidate vaccine could induce an anti-HIV specific immune response, volunteers were immunized by two injections of a water-in-oil emulsion containing a mixture of gp160 antigen together with selected peptides. Following immunization, lymphocytes were collected and stimulated in vitro with autologous HIV-1-infected cells. The results showed that immunization with soluble HIV-1 envelope was able to generate CD3+ CD8+ CTLs directed to gp160 antigen. The CTL response was restricted to class I molecule HLA-A2. The CTL response was comparable to that elicited by immunization with HIV-1-envelope recombinant vaccinia virus.
Cell Mol Biol (Noisy-le-grand) 1995 May
PMID:HIV-1 soluble antigens induced CD8+ cytotoxic T-cell responses in an immunized individual. 758 Aug 33

We have previously identified a VEINCTR peptide common to both the Fasmolecule and HIV-1 gp120. Here we report the characterization in PBMCs from HIV-1-infected individuals of a CD8+ class I restricted CTL activity directed towards this peptide. The peptide is highly conserved in various HIV-1 strains, being located at amino acid 287-293 (VEINCTR), within an epitope known as cell T epitope on the env protein of human immunodeficiency virus type-1. Cell cultures were obtained by polyclonal activation using autologous blast cells and CTL lines generated from frozen peripheral blood lymphocytes of HIV-1 seropositive donors by stimulation with the peptide and recombinant interleukin-2. The env-specific CTL turned out to kill autologous target cells infected with a recombinant vaccinia virus containing the env gene of HIV-1 or pulsed with peptide. Specificity was determined using shorter peptides. The CTL activity was directed against autologous target cells presenting the heptapeptide which is site located in the Fas molecule, known to be functionally involved in T-cell apoptosis.
Cell Mol Biol (Noisy-le-grand) 1995 May
PMID:Cytotoxic T lymphocytes specific for the synthetic VEINCTR peptide, a sequence found within the Fas molecule and env gp120 in the blood of HIV-1 seropositive individuals. 758 Aug 39

RNA (guanine-7-)methyltransferase, the enzyme responsible for methylating the 5' cap structure of eukaryotic mRNA, was isolated from extracts of Saccharomyces cerevisiae. The yeast enzyme catalyzed methyl group transfer from S-adenosyl-L-methionine to the guanosine base of capped, unmethylated poly(A). Cap methylation was stimulated by low concentrations of salt and was inhibited by S-adenosyl-L-homocysteine, a presumptive product of the reaction, but not by S-adenosyl-D-homocysteine. The methyltransferase sedimented in a glycerol gradient as a single discrete component of 3.2S. A likely candidate for the gene encoding yeast cap methyltransferase was singled out on phylogenetic grounds. The ABD1 gene, located on yeast chromosome II, encodes a 436-amino-acid (50-kDa) polypeptide that displays regional similarity to the catalytic domain of the vaccinia virus cap methyltransferase. That the ABD1 gene product is indeed RNA (guanine-7-)methyltransferase was established by expressing the ABD1 protein in bacteria, purifying the protein to homogeneity, and characterizing the cap methyltransferase activity intrinsic to recombinant ABD1. The physical and biochemical properties of recombinant ABD1 methyltransferase were indistinguishable from those of the cap methyltransferase isolated and partially purified from whole-cell yeast extracts. Our finding that the ABD1 gene is required for yeast growth provides the first genetic evidence that a cap methyltransferase (and, by inference, the cap methyl group) plays an essential role in cellular function in vivo.
Mol Cell Biol 1995 Aug
PMID:Yeast mRNA cap methyltransferase is a 50-kilodalton protein encoded by an essential gene. 762 11

The use of selected and nonselected markers for obtaining vaccinia virus recombinants is examined. The advantages of various selection systems are discussed.
Mol Biol (Mosk)
PMID:[Use of markers for selecting recombinant vaccinia viruses]. 772 66

A recombinant vaccinia virus was used to express a mutation in the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein gp120-gp41. In this mutant protein, the second amino acid in the N-terminal region of gp41 has been converted from a hydrophobic valine residue to the polar glutamate. When recombinant vaccinia viruses encoding wild-type HIV-1 envelope glycoprotein infect a lymphocyte cell line lacking CD4, the cells express the HIV-1 envelope glycoprotein gp120-gp41 and are able to fuse with a CD4(4) T lymphocyte cell line. Cells expressing the mutant envelope glycoprotein are unable to fuse with CD4(4) T lymphocytes. When both viruses infect CD4- cells simultaneously, there is an inhibition of fusion to CD4+ cells with an increasing fraction of the virus encoding the mutated envelope glycoprotein. Interestingly, when the opposing, or CD4+ target cells are infected with the mutation-expressing virus, while CD4- cells are infected with wild-type envelope-expressing virus, a similar inhibition of fusion is observed. This suggests that the mutated envelope glycoprotein does not need to reside in the same membrane as the wild-type protein it inhibits.
Mol Membr Biol
PMID:A trans-dominant mutation in human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein gp41 inhibits membrane fusion when expressed in target cells. 774 81

Since infection with Leishmania species induces CD4+ and CD8+ anti-leishmania T cells, we assessed protection against malaria by immunization with Leishmania enriettii transfected with the gene encoding the Plasmodium yoelii circumsporozoite protein (PyCSP). The recombinant plasmid appeared to be a circular episome in the host cells. Reverse transcription PCR showed that the PyCSP was trans-spliced by the addition of the 39-bp spliced leader of L. enriettii at its 5' end. The transfectant expressed a protein in a pattern similar to that found in the sporozoite itself. Immunofluorescence and immunoelectron microscopy indicated that PyCSP was abundantly expressed on the surface of the parasite. Mice immunized with the transfectant produced antibodies to sporozoites, had a delay in onset of parasitemia after challenge, and 4 of 22 (18%) were completely protected. The protected mice had cytotoxic T lymphocytes against the PyCSP. Immunization with recombinant vaccinia, Salmonella typhimurium, and pseudorabies virus expressing the PyCSP induces excellent immune responses, but has not been shown to protect against challenge. Thus, the modest protection found in these initial studies represents a step forward. After further work Leishmania may prove to be an important live vector vaccine system for induction of protective immune responses.
Mol Biochem Parasitol 1995 Feb
PMID:Partial protection against malaria by immunization with Leishmania enriettii expressing the Plasmodium yoelii circumsporozoite protein. 777 79


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