Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.7.49 (reverse transcriptase)
 31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Diphosphates of N-(2-phosphonylmethoxyethyl) derivatives of heterocyclic bases were studied in the endogenous oligo(dT)12-18 primed reaction of reverse transcriptase from detergent-disrupted AMV(MAV) retrovirions. These diphosphates (analogues of nucleotide 5'-triphosphates) exhibited an inhibitory activity towards reverse transcriptase. This inhibitory activity was dependent on the character of the heterocyclic base and decreased in the order: 2-aminoadenine greater than adenine greater than guanine much greater than cytosine much greater than thymine greater than uracil. The 2-aminoadenine derivative was more potent than either AZT-TP or ddTTP, while PMEApp had approximately the same potency as the two reference compounds (IC50 approximately 1 microM at 20 microM competing substrate). This finding is consistent with the antiviral activity of the parent nucleotide analogues against retroviruses (including HIV).
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PMID:Inhibition of avian myeloblastosis virus reverse transcriptase by diphosphates of acyclic phosphonylmethyl nucleotide analogues. 169 92

Several N-(S)-(3-hydroxy-2-phosphonylmethoxypropyl) (HPMP) and N-(2-phosphonylmethoxyethyl) (PME) derivatives of purine bases (adenine, guanine, 2-aminoadenine, 3-deazaadenine) and cytosine inhibit the growth of various DNA viruses. PME-derivatives (PMEA, PMEG and PMEDAP) are also active against retroviruses. Both types of nucleotide analogues undergo phosphorylation by cellular nucleotide kinases to their mono- and diphosphates. The phosphorylation with crude extracts of L-1210 cells is potentiated by an ATP-regenerating system. HPMPA is phosphorylated faster than PMEA with or without the ATP-regenerating system. The HPMP and PME analogues inhibit several virus-encoded target enzymes and their cellular counterparts: (1) HSV-1 DNA polymerase is inhibited by the diphosphates of the PME series; the virus-encoded enzyme is more sensitive than HeLa DNA pol alpha and beta. PMEApp terminates the growing DNA chain; it specifically replaces dATP. HPMPApp also acts as an alternative substrate of dATP, but, in contrast with PMEApp, it permits limited chain growth. (2) Diphosphates of both series inhibit HSV-1 ribonucleotide reductase; the greatest inhibition of CDP reduction to dCDP is exhibited by HPMPApp and PMEApp. The enzyme isolated from a PMEA-resistant HSV-1 mutant proved less sensitive to PMEApp, hydroxyurea and HPMPApp. (3) Diphosphates of PME derivatives efficiently inhibit AMV(MAV) reverse transcriptase. (4) The purine HPMP and PME analogues and, even more so, their monophosphate derivatives inhibit purine nucleoside phosphorylase from L-1210 cells.
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PMID:Acyclic nucleotide analogues: synthesis, antiviral activity and inhibitory effects on some cellular and virus-encoded enzymes in vitro. 169 93

Unintegrated MAV-2(O) DNA was isolated from infected chicken embryo fibroblasts and inserted into the lambda bacteriophage vector lambda gtWES lambda B. Three x 10(6) bacteriophage plaques were screened, yielding a total of seven clones, six of which contained DNA representing the complete MAV-2(O) genome. Viral DNA was isolated from four of the clones and was used to transfect chicken embryo fibroblasts. All four clones produced virus as monitored by reverse transcriptase assay. When the four cloned viruses were inoculated into 10-day-old embryos, all hatched chickens developed osteopetrosis. One clone, lambda 9, induced osteopetrosis at a rate of onset and severity identical to that induced by the MAV-2(O) parental stock. This clone was selected for further study. To facilitate restriction mapping, the viral DNA from lambda 9 was subcloned into plasmid vector pUC 12 to construct a plasmid called p9. Cleavage of p9 DNA with single and multiple restriction endonucleases and hybridization with gene-specific probes identified the restriction fragments obtained. A comprehensive restriction map of cloned MAV-2(O) was generated and is compared with published maps and sequences of other avian retroviruses.
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PMID:Preparation of a detailed restriction map of the avian leukosis virus MAV-2(O). 215 99

Immune function is likely to be shaped by multiple infections over time. Infection with one pathogen can confer cross-protection against heterologous pathogens. We tested the hypothesis that latent murine gammaherpesvirus 68 (gammaHV68) infection modulates host inflammatory responses and susceptibility to mouse adenovirus type 1 (MAV-1). Mice were infected intranasally (i.n.) with gammaHV68. 21 days later, they were infected i.n. with MAV-1. We assessed cytokine and chemokine expression by quantitative reverse transcriptase real-time PCR, cellular inflammation by histology, and viral loads by quantitative real-time PCR. Previous gammaHV68 infection led to persistently upregulated IFN-gamma in lungs and spleen and persistently upregulated CCL2 and CCL5 in the lungs. Previous gammaHV68 infection amplified MAV-1-induced CCL5 upregulation and cellular inflammation in the lungs. Previous gammaHV68 infection was associated with lower MAV-1 viral loads in the spleen but not the lung. There was no significant effect of previous gammaHV68 on IFN-gamma expression or MAV-1 viral loads when the interval between infections was increased to 44 days. In summary, previous gammaHV68 infection modulated lung inflammatory responses and decreased susceptibility to a heterologous virus in an organ- and time-dependent manner.
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PMID:Gammaherpesvirus modulation of mouse adenovirus type 1 pathogenesis. 1876 96

Severe dwarfing, yellowing, and crop failure were observed on barley in northeastern Spain during March and April of 2003. Leaves from 106 plants collected from 15 barley fields were analyzed using enzyme-linked immunosorbent assay (ELISA) with commercial antisera (Loewe Biochemica, Munich) specific for Barley mild mosaic virus (BaMMV), Barley yellow mosaic virus (BaYMV), the PAV and MAV serotypes of Barley yellow dwarf virus (BYDV), Barley yellow striate mosaic virus (BYSMV), Barley stripe mosaic virus (BSMV), Brome mosaic virus (BMV), Brome streak mosaic virus, (BStMV), Cereal yellow dwarf virus (CYDV), Wheat streak mosaic virus (WSMV), Wheat spindle streak mosaic virus (WSSMV), Soilborne cereal mosaic virus (SBCMV), and Wheat dwarf virus (WDV). In 70 samples, BYDV-PAV was the sole virus detected; in 20 other samples, this virus was detected in association with WDV, WSMV, BaMMV, and/or BaYMV. Mixed infections were further analyzed using reverse transcriptase-polymerase chain reaction (RT-PCR) or PCR with specific primers that amplify 445 bp of BaMMV (3), 433 bp of BaYMV (1), 600 bp of WSMV (primer 1: 5'CGAAACGCAGCG TTATTTC3', primer 2: 5'CATCTGAAG GGCTTGACG3'), and 1,200 bp of WDV (4). Eight samples gave the expected amplicons for WDV, two samples gave the expected amplicon for BaMMV, and one sample gave the BaMMV and BaYMV amplicons. No samples gave the amplicon for WSMV. In addition, 10 samples that were positive with ELISA for BYDV, either as a single or as multiple infections with other viruses, were analyzed with specific primers that amplify 600 bp of the BYDV genome (2) and all gave the expected RT-PCR product. ELISA and RT-PCR results agreed completely for WDV and BYDV samples, but agreed poorly for BaMMV and BaYMV (three of seven ELISA-positive samples). PCR products of WDV were subsequently cloned and sequenced. Sequence analysis confirmed the presence of WDV in these barley samples. This report shows the high occurrence of BYDV in barley fields and its association with BaMMV, BaYMV, and WDV infections that induces barley crop failure. To our knowledge, this is the first detection of WDV in Spain. References: (1) M. A. Achon et al. Plant Dis.87:1004, 2003. (2). E. S. G. Canning et al. J. Virol. Methods 56:191, 1996. (3) D. Hariri et al. Eur. J. Plant Pathol. 106:365, 2000. (4) A. Kvarnheden et al. Arch Virol. 147:206, 2002.
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PMID:First Detection of Wheat dwarf virus in Barley in Spain Associated with an Outbreak of Barley Yellow Dwarf. 3078 Oct 39

The Great Plains of the United States is a region comprised of approximately 45 million hectares of grasslands where several economically important cereal crops are grown. Arthropod-transmitted, cereal-infecting viruses vary in incidence from year-to-year and are often difficult to detect in large acreages. To facilitate the detection of economically important viruses of cereals that often exist in co-infections, a multiplex reverse transcriptase PCR (RT-PCR) platform assay was developed. This method can be used in combination with high resolution melting (HRM) to detect and allow for discrimination between three arthropod-transmitted plant viruses; Wheat streak mosaic virus (WSMV), Maize mosaic virus (MMV) and Barley yellow dwarf virus (BYDV). Multiplex PCR in combination with HRM allowed for successful detection of WSMV, MMV, and BYDV, as well as discrimination between three BYDV species, BYDV-PAS, BYDV-PAV and BYDV-MAV. All primer pairs amplified products of the predicted size. The BYDV-RT-PCR primers amplified products of identical length for all three species of BYDV. HRM was then used to discriminate between these products by determining significant differences between the melting rates for each (p < 0.05). This study demonstrates the flexibility of combining multiplex PCR with HRM to increase the specificity of plant virus diagnostics based on the needs of the diagnostician performing the assay.
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PMID:Combining multiplex PCR and high-resolution melting for the detection and discrimination of arthropod transmitted viruses of cereals. 3198 68