Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019158 (hepatitis)
 30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In elucidating functionally important single-stranded loop regions derived mainly from three models in genomic hepatitis delta virus (HDV) ribozyme possessing self-cleavage activity, we have constructed several internal deletion variants of the HDV133 molecule (654-786 nt on genomic RNA) by oligonucleotide-directed mutagenesis. When self-cleavage activities were compared among variants, the HDV133DI-1 (deletion of 701-718 nt) and HDV133DI-3 (deletion of 740-752 nt) ribozyme could maintain their self-cleavage activity, despite at reduced level. However, the activity could be regained in both mutants by some extent under partially denaturing conditions. These results suggest that the above two single-stranded RNA loop regions in HDV ribozyme are not part of the catalytic core but might be involved in the stability of the molecule. In contrast, deletion mutants such as HDV133DI-2 (deletion of 696-722 nt), HDV88DI-1 (deletion of 701-718 nt), HDV88DI-2 (deletion of 696-722 nt), and HDV88DI-4 (deletion of 733-760 nt) abolished catalytic activity. These results suggest that the remaining single-stranded regions of bases between 726-731 and 762-766 in the HDV88 ribozyme may be the potential regions to interact with Mg2+ ions.
 ...
PMID:Deletion of internal sequence on the HDV-ribozyme: elucidation of functionally important single-stranded loop regions. 154 71

The two sequences that define the self-cleaving elements from the genomic and antigenomic RNA of hepatitis delta virus were folded into secondary structures with similar features. Evidence in support of the two models was obtained from limited ribonuclease digestion of genomic and antigenomic RNA fragments containing the sequence 3' of the cleavage site. Under conditions where the rates of self-cleavage are enhanced by addition of 5 M urea (2-10 mM Mg2+ at 37 degrees C), ribonucleases T1, U2, A and V1 generated digestion patterns consistent with the proposed RNA structures. The evidence for a relatively stable structure in urea when Mg2+ is present suggests that denaturant-enhanced rates of self-cleavage could result from destabilization of competing inactive structures.
 ...
PMID:Evidence that genomic and antigenomic RNA self-cleaving elements from hepatitis delta virus have similar secondary structures. 192 26

Serum Zn2+, Cu2+, and Mg2+ were assayed in patients with chronic persisting hepatitis HBsAg-positive. Significantly decreased serum magnesium with increased serum copper levels were noted.
 ...
PMID:[Trace elements: zinc, copper and magnesium in patients with chronic persisting hepatitis--evaluation of changes during therapy]. 208 28

Self-cleavage of a polyribonucleotide containing an autocleaving sequence from the genomic strand of hepatitis delta virus was enhanced by conditions that destabilized RNA structure. Self-cleavage of the transcripts used in this study required Mg2+ (or another divalent cation), and in the absence of denaturants, maximum cleavage was observed at very low Mg2+ concentrations (0.05-0.1 mM). However, at 37 degrees C and in the presence of 2-10 mM Mg2+ the rate of cleavage was increased as much as 50-fold with the addition of urea to 5 M or formamide to 10 M. Cleavage was prevented by higher concentrations of the same reagents (9.5 M urea or 22.5 M formamide), presumably because a structure required for self-cleavage is disrupted by strongly denaturing conditions. In contrast to a previous report [Wu, H.-N., & Lai, M. M. C. (1989) Science 243, 652-654], we find that chelating Mg2+ with EDTA terminates the cleavage reaction without promoting measurable amounts of ligation of the cleavage products. The ability of denaturants to promote rapid self-cleavage in vitro raises the possibility that an unidentified factor could have a similar effect in vivo.
 ...
PMID:Self-cleavage of hepatitis delta virus genomic strand RNA is enhanced under partially denaturing conditions. 226 58

A 148-nucleotide subfragment of hepatitis delta virus RNA was shown to undergo cleavage and ligation reversibly. The direction of the reaction is determined by the presence or absence of Mg2+ ions, with the presence of Mg2+ favoring the cleavage reaction. Ligation requires specific conformation of the RNA molecules involved and occurs only between two cleaved RNA fragments that are still held together by hydrogen bonds. The ligation reaction occurs rapidly on removal of Mg2+ by EDTA. This represents a new class of RNA enzymes.
 ...
PMID:Reversible cleavage and ligation of hepatitis delta virus RNA. 249 77

The effects of aevite and riboflavin on electrolyte balance in the vessel wall were studied in toxic hepatitis in the cat. Significant changes in the contents of Na+, K+, Ca2+ and Mg2+ ions in the hepatic blood vessels were found in all periods of observation. The treatment of toxic hepatitis with aevite and riboflavin results in normalization of electrolyte balance of the vessel wall.
 ...
PMID:[Effect of aevite and riboflavin on the electrolyte balance in the wall of the hepatic blood vessels in experimental toxic hepatitis]. 370 81

The multiplication of mouse hepatitis virus (MHV) was inhibited by the treatment of infected cells with MgSO4 at concentrations higher than 50 mM. The inhibition of viral multiplication was more effective with the treatment of cells at the early stage of infection using MgSO4 than at the late stage. Viral adsorption to the cells was not inhibited by MgSO4 and pretreatment of the cells with MgSO4 did not show an inhibitory effect on the RNA synthesis of MHV. The synthesis of viral RNA was inhibited more effectively by the treatment of infected cells with MgSO4 at 0-2 and 2-4 h postinfection (p.i.) than at 4-6 h p.i. The present study suggests that the stage at which viral multiplication is susceptible to MgSO4 may be the early stage of viral transcription and that Mg2+ may be a useful tool for the analysis of the early stage of MHV infection.
 ...
PMID:The inhibitory effects of MgSO4 on the multiplication and transcription of mouse hepatitis virus. 779 68

To identify the divalent metal ions that can support the self-cleavage activity of the genomic ribozyme of human hepatitis delta virus (HDV), we tested the activity of various divalent metal ions in the ribozyme reactions catalyzed by HDV88 (683-770 nt) and 88DI3 (HDV88 with the sequence from 740-752 nt deleted). Among various metal ions tested, Mg2+, Mn2+, Ca2+ and Sr2+ efficiently supported the self-cleavage reactions of the HDV88 and 88DI3 ribozymes. In the case of the 88DI3 ribozyme, other divalent metal ions, such as Cd2+, Ba2+, Co2+, Pb2+ and Zn2+, were also able to support the self-cleavage reaction to some extent (< 10%). In the presence of spermidine (0.5 mM), the cleavage reaction was promoted at lower concentrations of effective divalent metal ions. The HDV ribozyme represents the only example of ribozyme to date of a ribozyme that catalyzes the self-cleavage reaction in the presence of Ca2+ ions as efficiently as it does in the presence of Mg2+ ions.
 ...
PMID:Self-cleavage activity of the genomic HDV ribozyme in the presence of various divalent metal ions. 834 2

Specific features of a model for the secondary structure of the self-cleaving RNA sequences (ribozymes) of hepatitis delta virus were rigorously tested. Using a self-cleaving form of the antigenomic sequence, mutations were made in the 5' and 3' sequences of each of four duplex regions within the proposed ribozyme structure. Precursor RNA from each variant sequence was prepared and the kinetics of cleavage in 10 mM Mg2+ at 37 degrees was examined. The data was quantified to determine an end point and a first-order rate constant for cleavage with each mutant by fitting the data to the exponential form of the first-order rate equation. With regard to the final extent of cleavage, most mutations in these regions appeared to have little effect, however, the kinetics indicated that disruption of the potential for basepairing resulted in dramatic decreases in the rate constant for cleavage. These results are consistent with the idea that most of the mutations affected ribozyme activity rather than an equilibrium between precursor and cleavage products. Mutations that reduced rates were compensated by changes that restored the potential for Watson-Crick pairing. Ribonuclease probing of ribozyme variants containing mismatches and compensatory changes allowed direct correlation of structural changes with the mutations. This provided an independent validation of the functional kinetic assay. Thus, site-directed mutagenesis was consistent with a proposed ribozyme secondary structure containing 4 distinct base-paired regions.
 ...
PMID:Experimental evidence for the secondary structure of the hepatitis delta virus ribozyme. 850 19

Human hepatitis delta virus (HDV) poses a health threat in populations where chronic hepatitis B is endemic. It is a single-stranded RNA virus of 1700 nucleotides and both genomic and antigenomic sequences contain ribozymes which are important for viral replication. Using ribozyme constructs we show that several classes of antibiotics inhibit the self-cleavage reaction of the HDV ribozyme. Antibiotics of the aminoglycoside, peptide and tetracycline classes all inhibit HDV cleavage in vitro at micromolar concentrations. Neomycin (an aminoglycoside) inhibits HDV self-cleavage with a Ki value of 28 (+/- 10) microM. Neomycin inhibition can be reversed by increasing magnesium ion concentration in a competitive manner. Lead acetate cleaves positions G76, A42 and G28, which surround the ribozyme cleavage site. Both Mg2+ and neomycin prevent lead cleavage. Footprinting experiments using base-specific chemical probes revealed enhanced modifications of a set of bases by neomycin, overlapping with the above mentioned lead cleavages. These observations may indicate that neomycin directly displaces divalent metal ions essential for catalysis.
 ...
PMID:Inhibition of the self-cleavage reaction of the human hepatitis delta virus ribozyme by antibiotics. 868 94


1 2 3 Next >>