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91.
Measles virus infects and suppresses proliferation of T lymphocytes from transgenic mice bearing human signaling lymphocytic activation molecule
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Hahm B Arbour N Naniche D Homann D Manchester M Oldstone MB 《Journal of virology》2003,77(6):3505-3515
Humans are the only natural reservoir of measles virus (MV), one of the most contagious viruses known. MV infection and the profound immunosuppression it causes are currently responsible for nearly one million deaths annually. Human signaling lymphocytic activation molecule (hSLAM) was identified as a receptor for wild-type MV as well as for MV strains prepared as vaccines. To better evaluate the role of hSLAM in MV pathogenesis and MV-induced immunosuppression, we created transgenic (tg) mice that expressed the hSLAM molecule under the control of the lck proximal promoter. hSLAM was expressed on CD4(+) and CD8(+) T cells in the blood and spleen and also on CD4(+), CD8(+), CD4(+) CD8(+), and CD4(-) CD8(-) thymocytes. Wild-type MV, after limited passage on B95-8 marmoset B cells, and the Edmonston laboratory strain of MV infected hSLAM-expressing cells. There was a direct correlation between the amount of hSLAM expressed on the cells' surface and the degree of viral infection. Additionally, MV infection induced downregulation of receptor hSLAM and inhibited cell division and proliferation of hSLAM(+) but not hSLAM(-) T cells. Therefore, these tg mice provide the opportunity for analyzing and comparing MV-T cell interactions and MV pathogenesis in cells expressing only the hSLAM MV receptor with those of tg mice whose T cells selectively express another MV receptor, CD46. 相似文献
92.
Design of novel analogues with potent antibiotic activity based on the antimicrobial peptide, HP(2-9)-ME(1-12) 总被引:2,自引:0,他引:2
To develop novel antibiotic peptides useful as therapeutic drugs, a number of analogues were designed to increase the hydrophobic helix region either by Trp-substitution or net positive charge increase by Lys-substitution, from HP(2-9)-ME(1-12). The antibiotic activities of these peptides were evaluated using bacterial (Salmonella tryphimurium, Proteus vulgaris, Bacillus subtilis and Staphylococcus aureus), fungi (Saccharomyces cerevisiae, Trichosporon beigelii and Candida albicans), tumor and human erythrocyte cells. The substitution of Lys for Thr at position 18 and 19 of HP(2-9)-ME(1-12) (HM5) increased activity against Proteus vulgaris and fungal strains without hemolysis. In contrast, substitution of Trp for Lys and Thr at positions 2, 15 and 19 of HP(2-9)-ME(1-12), respectively (HM3 and HM4), decreased activity but increased hemolysis against human erythrocytes. This suggests that an increase in positive charge increases antimicrobial activity whereas an increase in hydrophobicity by introducing Trp residues at C-terminus of HP(2-9)-ME(1-12) causes a hemolytic effect. Circular dichroism spectra suggested that the alpha-helical structure of these peptides plays an important role in their antibiotic effect but that the alpha-helical property is not connected with the enhanced antibiotic activity. 相似文献
93.
The developmental stage-specific regulation of V(D)J recombination, a gene rearrangement process of antigen receptor gene segments, is tightly controlled in cells. Here we screened proteins uniquely or differentially expressed among three developmentally distinguishable B cells (pro-B, pre-B and mature B cells) using two-dimensional gel electrophoresis and mass spectrometry. Chromatin assembly factor 1 was uniquely expressed in pro-B cells. Purine nucleotide phosphorylase, LCK, E2A and many other unidentified proteins were dominantly present in the nucleus at the early stage of B cell development where the V(D)J recombination process occurs. Also, few proteins including guanidine nucleotide binding proteins were exclusively expressed in pre-B cell. Such findings can provide some information to help understand the developmental regulation of gene rearrangement occurring during B cell development. 相似文献
94.
Heterogeneous Nuclear Ribonucleoprotein L Interacts with the 3′ Border of the Internal Ribosomal Entry Site of Hepatitis C Virus
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Bumsuk Hahm Yoon Ki Kim Jong Heon Kim Tae Yoon Kim Sung Key Jang 《Journal of virology》1998,72(11):8782-8788
Translation initiation of hepatitis C virus (HCV) RNA occurs by internal entry of a ribosome into the 5′ nontranslated region in a cap-independent manner. The HCV RNA sequence from about nucleotide 40 up to the N terminus of the coding sequence of the core protein is required for efficient internal initiation of translation, though the precise border of the HCV internal ribosomal entry site (IRES) has yet to be determined. Several cellular proteins have been proposed to direct HCV IRES-dependent translation by binding to the HCV IRES. Here we report on a novel cellular protein that specifically interacts with the 3′ border of the HCV IRES in the core-coding sequence. This protein with an apparent molecular mass of 68 kDa turned out to be heterogeneous nuclear ribonucleoprotein L (hnRNP L). The binding of hnRNP L to the HCV IRES correlates with the translational efficiencies of corresponding mRNAs. This finding suggests that hnRNP L may play an important role in the translation of HCV mRNA through the IRES element. 相似文献
95.
The yiaE Gene,Located at 80.1 Minutes on the Escherichia coli Chromosome,Encodes a 2-Ketoaldonate Reductase
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An open reading frame located in the bisC-cspA intergenic region, or at 80.1 min on the Escherichia coli chromosome, encodes a hypothetical 2-hydroxyacid dehydrogenase, which was identified as a result of the E. coli Genome Sequencing Project. We report here that the product of the gene (yiaE) is a 2-ketoaldonate reductase (2KR). The gene was cloned and expressed with a C-terminal His tag in E. coli, and the protein was purified by metal-chelate affinity chromatography. The determination of the NH2-terminal amino acid sequence of the protein defined the translational start site of this gene. The enzyme was found to be a 2KR catalyzing the reduction of 2,5-diketo-d-gluconate to 5-keto-d-gluconate, 2-keto-d-gluconate (2KDG) to d-gluconate, 2-keto-l-gulonate to l-idonate. The reductase was optimally active at pH 7.5, with NADPH as a preferred electron donor. The deduced amino acid sequence showed 69.4% identity with that of 2KR from Erwinia herbicola. Disruption of this gene on the chromosome resulted in the loss of 2KR activity in E. coli. E. coli W3110 was found to grow on 2KDG, whereas the mutant deficient in 2KR activity was unable to grow on 2KDG as the carbon source, suggesting that 2KR is responsible for the catabolism of 2KDG in E. coli and the diminishment of produced 2KDG from d-gluconate in the cultivation of E. coli harboring a cloned gluconate dehydrogenase gene.We previously reported the cloning and expression of a gene cluster encoding three subunits of membrane-bound gluconate dehydrogenase (GADH) from Erwinia cypripedii in Escherichia coli (26). In the course of further study on the conversion of d-gluconate to 2-keto-d-gluconate (2KDG) with a recombinant E. coli strain, we observed that the level of 2KDG produced in the medium gradually decreased after the exhaustion of d-gluconate in the medium (see Fig. Fig.1).1). In an effort to find the reason, the NADPH-dependent reductase activity catalyzing the conversion of 2KDG to d-gluconate was detected in extracts of E. coli cells. This result suggested the existence of enzymes involved in ketogluconate metabolism in E. coli, as reported for several species of the genera Corynebacterium, Brevibacterium, Erwinia, Acetobacter, Gluconobacter, Serratia, and Pseudomonas (20, 23, 25). In Erwinia, Acetobacter, Gluconobacter, Serratia, and Pseudomonas, oxidation of glucose to ketogluconates such as 2KDG, 5-keto-d-gluconate (5KDG), and 2,5-diketo-d-gluconate (25DKG) has been shown to proceed via membrane-bound dehydrogenases, which are linked to the electron transport chain (2, 21). The ketogluconates or their phosphorylated forms are unique substrates in that they enter into central metabolism only after they are reduced by NADPH-dependent reductases (20, 23). NADPH-dependent 2-ketoaldonate reductase (2KR), which catalyzes the reduction of 2KDG to d-gluconate, 25DKG to 5KDG, and 2-keto-l-gulonate (2KLG) to l-idonate (IA), has been purified and characterized from Brevibacterium ketosoreductum (25) and Erwinia herbicola (23). Even if the substrate specificity has not been examined with 25DKG as a substrate, 2KDG reductases from acetic acid bacteria also catalyze the reduction of 2KLG to IA as well as of 2KDG to d-gluconate (1).Open in a separate windowFIG. 1Time course of bioconversion of d-gluconate to 2KDG by E. coli harboring the cloned GADH gene. E. coli W3110(pGA313) was grown in a 2-liter fermentor at 37°C with aeration at 1 vvm and agitation at 500 rpm.Until now, no ketoaldonate reductase has been reported for E. coli. We report here that the product of the yiaE gene, located in the bisC-cspA intergenic region at 80.1 min on the E. coli chromosome, is a 2KR; in addition, the diminishment of produced 2KDG from d-gluconate in the cultivation of recombinant E. coli harboring a cloned membrane-bound GADH gene is due to 2KR as the cytosolic enzyme responsible for conversion of 2KDG to d-gluconate. We found also that E. coli W3110 grows on 2KDG as the sole carbon source. 相似文献
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100.
Effects of the hinge region of cecropin A(1-8)-magainin 2(1-12), a synthetic antimicrobial peptide, on liposomes, bacterial and tumor cells 总被引:9,自引:0,他引:9
A 20-residue hybrid peptide (CA(1-8)-MA(1-12): KWKLFKKIGIGKFLHSAKKF-NH(2)) incorporating 1-8 residues of cecropin A (CA) and 1-12 residues of magainin 2 (MA) has potent antibiotic activity without hemolytic activity. In order to investigate the effects of the flexible hinge sequence, Gly-Ile-Gly of CA(1-8)-MA(1-12) (CA-MA) on antibiotic activity, CA-MA and its three analogues, CA-MA1, CA-MA2 and CA-MA3 were synthesized. The Gly-Ile-Gly sequence of CA-MA was deleted in CA-MA1 and replaced with Pro and Gly-Pro-Gly in CA-MA2 and CA-MA3, respectively. CA-MA1 and CA-MA3 caused a significant decrease in the bactericidal rate against Escherichia coli and Bacillus subtilis and the tumoricidal activity against four different tumor cells, and the PC/PS (4:1, w/w) vesicle-aggregating and disrupting activities. However, CA-MA2 showed a similar bactericidal rate and antitumor, vesicle-aggregating and disrupting activities, as compared with CA-MA. These results suggested that the flexibility or beta-turn induced by Gly-Ile-Gly or Pro in the central part of CA-MA may be important in the electrostatic interaction of the cationic short alpha-helical region in the N-terminus with the cell membrane surface and the hydrophobic interaction of amphipathic alpha-helical region in the C-terminus with the hydrophobic acyl chains in the cell membrane. CA-MA3 exhibited lower activity in antibacterial, antitumor, and vesicle-aggregating and disrupting activities than CA-MA and CA-MA2. This result suggested that the excessive beta-turn structure by Gly-Pro-Gly in CA-MA3 seems to interrupt the ion channel/pore formation on the lipid bilayer. It was concluded that the appropriate flexibility or beta-turn structure provided by the central hinge is responsible for the effective antibiotic activity of the antimicrobial peptides with the helix-hinge-helix structure. 相似文献