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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous studies show that the reverse transcriptase (RT) of human immunodeficiency virus type-1 (HIV-1) and RT-derived peptides interact with and inhibit the viral integrase (IN). In the present study, we have performed the complementary study by screening a complete library of HIV-1 IN-derived peptides for their effects on the RT. We have identified a 20-residues long peptide, derived from the IN (residues 46-65) that binds the RT and inhibits its DNA-polymerase activities (without affecting the ribonuclease-H activity). The full 20-residues sequence is required for maximal inhibition. This inhibition is non-competitive and probably results from obstructing the formation of RT-DNA complexes by the peptide. The data and the molecular docking model presented suggest that this inhibition is probably caused by a steric hindrance or conformational changes of the RT. These results can facilitate the development of novel and specific peptide-based HIV-1 RT inhibitors that might help in the fight against AIDS.
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PMID:Inhibition of human immunodeficiency virus type-1 reverse transcriptase by a novel peptide derived from the viral integrase. 1725 75

The effect of the total positive charge in the RNA-binding domain of chemical ribonucleases that are conjugates of bisquaternary salts of diazabicyclo[2.2.2]octane and imidazol on the cleavage of an HIV-1 RNA fragment was studied. An increase in the positive charge from +2 to +4 was shown to result in a significant growth in the ribonuclease activity. Possible mechanisms of the interactions between structural moieties of chemical ribonucleases and RNA that enable an effective catalysis of the cleavage of phosphodiester bonds are discussed.
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PMID:[Chemical ribonucleases: VII. Effect of positively charged RNA-binding domains and hydrophobic fragments of the conjugates based on 1,4-diazabicyclo[2.2.2]octane and imidazol on their ribonuclease activity]. 1747 86

The crystal structure of ribonuclease HI from the hyperthermophilic archaeon Sulfolobus tokodaii (Sto-RNase HI) was determined at 1.6 A resolution. Sto-RNase HI exhibits not only RNase H activity but also double-stranded RNA-dependent ribonuclease (dsRNase) activity. The main-chain fold and steric configurations of the four acidic active-site residues of Sto-RNase HI are very similar to those of other type 1 RNases H. However, Arg118 of Sto-RNase HI is located at the position in which His124 of E. coli RNase HI, His539 of HIV-1 RNase H, and Glu188 of Bacillus halodurans RNase H are located. The mutation of this residue to Ala considerably reduced both the RNase H and dsRNase activities without seriously affecting substrate binding, suggesting that Arg118 is involved in catalytic function. This residue may promote product release by perturbing the coordination of the metal ion A as proposed for Glu188 of B. halodurans RNase H. In addition, the extreme C-terminal region of Sto-RNase HI is anchored to its core region by one disulfide bond and several hydrogen bonds. Differential scanning calorimetry measurements indicated that Sto-RNase HI is a hyperstable protein with a melting temperature of 102 degrees C. The mutations of the cysteine residues forming disulfide bond or elimination of the extreme C-terminal region greatly destabilized the protein, indicating that anchoring of the C-terminal tail is responsible for hyperstabilization of Sto-RNase HI.
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PMID:Crystal structure of type 1 ribonuclease H from hyperthermophilic archaeon Sulfolobus tokodaii: role of arginine 118 and C-terminal anchoring. 1789 5

A ribonuclease, RNase T-tat, specifically designed to hydrolyze the TAR RNA of HIV-1 virus has been engineered. The protein was made by domain swapping the TAT peptide at the loop 3 position of ribonuclease T1. The RNase T-tat maintains a guanine-specific RNA hydrolytic activity, and characteristically displayed a specific affinity for the TAR RNA of HIV-1. In the in vitro and in vivo assays, the RNase T-tat preferentially inhibited the expression of TAR-bearing mRNA through cis-TAR targeting, suggesting that RNase T-tat may be potentially useful for the disruption of the initial stage of the transcription process of HIV-1 virus.
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PMID:Creating a ribonuclease T-tat that preferentially recognizes and hydrolyzes HIV-1 TAR RNA in vitro and in vivo. 1808 2

The interaction between human immunodeficiency virus type 1 (HIV-1) and RNA silencing pathways is complex and multifaceted. Essential for efficient viral transcription and supporting Tat-mediated transactivation of viral gene expression, the trans-activation responsive (TAR) element is a structured RNA located at the 5' end of all transcripts derived from HIV-1. Here, we report that this element is a source of microRNAs (miRNAs) in cultured HIV-1-infected cell lines and in HIV-1-infected human CD4+ T lymphocytes. Using primer extension and ribonuclease (RNase) protection assays, we delineated both strands of the TAR miRNA duplex deriving from a model HIV-1 transcript, namely miR-TAR-5p and miR-TAR-3p. In vitro RNase assays indicate that the lack of a free 3' extremity at the base of TAR may contribute to its low processing reactivity in vivo. Both miR-TAR-5p and miR-TAR-3p down-regulated TAR miRNA sensor activity in a process that required an integral miRNA-guided RNA silencing machinery. miR-TAR-3p exerted superior gene downregulatory effects, probably due to its preferential release from HIV-1 TAR RNA by the RNase III Dicer. Our study suggests that the TAR element of HIV-1 transcripts releases functionally competent miRNAs upon asymmetrical processing by Dicer, thereby providing novel insights into viral miRNA biogenesis.
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PMID:Identification of functional microRNAs released through asymmetrical processing of HIV-1 TAR element. 1829 84

Shortly after starting to use the NucliSens EasyQ HIV-1 V1.1 system for HIV-1 RNA load testing, the number of invalid tests per assay run gradually increased. Within five days, approximately 50% of tests showed a total lack of amplification of the calibrator and in most cases also of the HIV-1 template. According to the manufacturer's specifications, the lysis buffer and three extraction buffers remain on the automated NucliSens easyMAG extraction system between assay runs. Therefore possible microbial contamination of these buffers was investigated, after they had been on the automated system for approximately one week. The NucliSens easyMAG extraction buffer 2 yielded bacterial growth identified as Acinetobacter baumannii. After regular decontamination of the machine's tubing system with 70% alcohol and storage of the buffers at 4 degrees C between assay runs were commenced, invalid results due to failed internal calibrator signal occurred no longer. It is likely that bacterial contamination of the buffer was the cause of assay failure, probably due to ribonuclease (RNase) activity. Bacterial contamination of PCR systems should be added to the list of potential hazards in diagnostic virology. This experience underlines the necessity of state-of-the-art assay design incorporating adequate internal controls and calibrators.
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PMID:Extraction buffer contaminated bacterially as a cause of invalid HIV-1 viral load results on the NucliSens EasyQ system. 1842 34

The incidence of maternal-to-fetal human immunodeficiency virus type 1 (HIV-1) transmission is 25-30% in absence of antiretroviral therapy, and is inversely associated with Human leukocyte antigens (HLA) class-I discordance. Based on our earlier report that mixed lymphocyte reactions (MLR) induce a ribonuclease (RNase) that inhibits HIV-1 replication, we proposed that maternal-fetal alloantigen stimulation activates factors that protect the fetus against vertically-transmitted infections. We investigate here whether the degree of mother-infant HLA discordance associates with the ability to produce anti-HIV-1 alloantigen-stimulated factor (ASF), and affects placental RNases. We also determine whether such HLA association is influenced by the mother's HIV-1 status. Paired maternal and cord blood leukocytes were tested for the induction of ASF by MLR, and typed for HLA-A and -B. The placentas were tested for mRNA expression of three RNases. Neonate anti-mother, but not mother anti-neonate MLR generated supernatants with anti-HIV-1 activity, that was associated with HLA class I discordance. This HLA association was not seen in the HIV-infected cohort. HLA class I discordance was also associated with expression of placental RNase 1. Our findings are consistent with the hypothesis that HLA class I discordance induces expression of RNases in the placenta that contribute to innate host resistance to HIV-1 and other viral infections.
Curr HIV Res 2008 Jun
PMID:Fetal-maternal HLA-A and -B discordance is associated with placental RNase expression and anti-HIV-1 activity. 1869 Oct 36

The dependence of hydrolytic activity of artificial ribonucleases toward an HIV-I RNA fragment, a 21-mer oligonucleotide, and tRNA Asp on the structure of the RNase mimetic was analyzed. The quantitative structure-activity relationship (QSAR task) was determined by the method of simplex representation of the molecular structure where the amounts of four-atom fragments (simplexes) of fixed structure, symmetry, and chirality served as descriptors. Not only the types of atoms participating in simplexes but also their physicochemical properties (e.g., partial charges, lipophilicities, etc.) were taken into account. This allowed the estimation of the relative role of various factors affecting the interaction of molecules under study with the corresponding biological target. The 2D QSAR models obtained by the method of projection to latent structures have quite satisfactory statistical indices (R2 = 0.82-0.96; Q2 = 0.73-0.89), which help predict the activities of new compounds. The electrostatic properties of ribonuclease atoms were shown to contribute significantly to the manifestation of the hydrolytic activity of ribonucleases in the case of the 21-mer oligonucleotide and tRNA. In addition, the structural fragments that most greatly contribute to the alteration of the hydrolytic activity of RNases were identified. The models obtained were used for the virtual screening and molecular design of new highly efficient RNase mimetics.
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PMID:[Artificial ribonucleases: quantitative analysis of the structure-activity relationship and new insight into the strategy of design of highly efficient RNase mimetics]. 1869 22

A protein exhibiting an N-terminal amino acid sequence with some similarity to imidazoleglycerol phosphate synthase was purified from fresh Capparis spinosa melon seeds. The purification protocol entailed anion exchange chromatography on DEAE-cellulose, cation exchange chromatography on SP-Sepharose, and finally gel filtration by fast protein liquid chromatography on Superdex 75. The protein was adsorbed using 20 mM Tris-HCl buffer (pH 7.4) and desorbed using 1 M NaCl in the starting buffer from the DEAE-cellulose column and SP-Sepharose column. The protein demonstrated a molecular mass of 38 kDa in gel filtration and sodium dodecyl sulfate-polyacrylamide gel electrophoresis, indicating that it was monomeric. The protein inhibited proliferation of hepatoma HepG2 cells, colon cancer HT29 cells and breast cancer MCF-7 cells with an IC(50) of about 1, 40 and 60 microM, respectively. It inhibited HIV-1 reverse transcriptase with IC(50) of 0.23 microM. It inhibited mycelial growth in the fungus, Valsa mali. It did not exhibit hemagglutinating, ribonuclease, mitogenic or protease inhibitory activities.
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PMID:A protein with antiproliferative, antifungal and HIV-1 reverse transcriptase inhibitory activities from caper (Capparis spinosa) seeds. 1901 43

Reaction of terbium triflate with a heptadentate ligand derivative of cyclen, L1 = 2-[7-ethyl-4,10-bis(isopropylcarbamoylmethyl)-1,4,7,10-tetraazacyclododec-1-yl]-N-isopropyl-acetamide, produced a new synthetic ribonuclease, [Tb(L1)(OTf)(OH(2))](OTf)(2).MeCN (C1). X-ray crystal structure analysis indicates that the terbium(III) center in C1 is 9-coordinate, with a capped square-antiprism geometry. While the terbium(III) center is tightly bound by the L1 ligand, two of the coordination sites are occupied by labile water and triflate ligands. In water, the triflate ligand is likely to be displaced, forming [Tb(L1)(OH(2))(2)](3+), which is able to effectively promote RNA cleavage. This complex greatly accelerates the rate of intramolecular transesterification of an activated model RNA phosphodiester, uridine-3'-p-nitrophenylphosphate (UpNP), with k(obs) = 5.5(1) x 10(-2) s(-1) at 21 degrees C and pH 7.5, corresponding to an apparent second-order rate constant of 277(5) M(-1) s(-1). By contrast, the analogous complex of an octadentate derivative of cyclen featuring only a single labile coordination site, [Tb(L2)(OH(2))](OTf)(3) (C2), where L2 = 2-[4,7,10-tris(isopropylcarbamoylmethyl)-1,4,7,10-tetraazacyclododec-1-yl]-N-isopropyl-acetamide, is inactive. [Tb(L1)(OH(2))(2)](3+) is also capable of hydrolyzing short transcripts of the HIV-1 transactivation response (TAR) element, HIV-1 dimerization initiation site (DIS) and ribosomal A-site, as well as formyl methionine tRNA (tRNA(fMet)), albeit at a considerably slower rate than UpNP transesterification (k(obs) = 2.78(8) x 10(-5) s(-1) for TAR cleavage at 37 degrees C, pH 6.5, corresponding to an apparent second-order rate constant of 0.56(2) M(-1)s(-1)). Cleavage is concentrated at the single-stranded "bulge" regions of these RNA motifs. Exploiting this selectivity, [Tb(L1)(OH(2))(2)](3+) was successfully employed in footprinting experiments, in which binding of the Tat peptide and neomycin B to the bulge region of the TAR stem-loop was confirmed.
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PMID:New macrocyclic terbium(III) complex for use in RNA footprinting experiments. 1911 12


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