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

Tranfusion-transmitted virus (TTV), a single-stranded circular DNA virus that chronically infects humans and other animals, displays a high degree of genetic diversity and was originally thought to be associated with hepatitis. The prevalences of TTV infection among different populations of humans and non-human primates from Venezuela have now been evaluated, using serum samples and three different detection tests. All three tests were PCR-based, one involving a hemi-nested PCR and primers based on the N22 open-reading-frame-1 region (N22-PCR), another employing 55 cycles with primers from the more conserved untranslated region (UTR-PCR), and the other using a hemi-nested PCR with primers from the same region (HUTR-PCR). The overall prevalences of human infection appeared much higher with the HUTR-PCR (52%) than with the N22-PCR (13%) or the UTR-PCR (5%). When the products amplified by N22-PCR from 28 human isolates of TTV were sequenced, only two genotypes of the virus were detected. The non-human sera tested came from primates kept in a zoo in north-western Venezuela. TTV DNA was detected, by HUTR-PCR, in both of the chimpanzee sera tested but not in any of the sera from the 11 New-World primates or the other 12 Old-World primates that were investigated. The results, particularly those of the HUTR-PCR, indicate that TTV infection is common in Venezuela, especially in populations, such as many Amerindian groups, who live under poor sanitary conditions. Although TTV infection may be relatively rare among non-human primates from the New World, this will have to be investigated further, using many more samples collected throughout the Americas.
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PMID:Infection with transfusion-transmitted virus (TTV) in humans and other primates in Venezuela. 1581 36

The woodchuck post-transcriptional regulatory element (WPRE) can naturally accumulate hepatitis transcripts in the cytoplasm, and has been recently exploited as an enhancer of transgene expression. The retention of mutant myotonic dystrophy protein kinase (DMPK) transcripts in the nucleus of myotonic dystrophy (DM) cells has an important pathogenic role in the disease, resulting in pleiotropic effects including delayed myoblast differentiation. In this study, we report the first use of WPRE as a tool to enhance nuclear export of an aberrantly retained messenger RNA. Stable cell lines expressing the normal and mutant DMPK 3' UTR (3' untranslated region) complementary DNA, with or without WPRE, were produced. It is noteworthy that WPRE stimulated extensive transport of mutant transcripts to the cytoplasm. This was associated with repair of the defective cellular MyoD levels and a subsequent increase in myoblast differentiation. These results provide the basis for a cellular model that can be exploited in DM and in the study of RNA transport mechanisms.
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PMID:Woodchuck post-transcriptional element induces nuclear export of myotonic dystrophy 3' untranslated region transcripts. 1583 71

TT virus (TTV) is a naked, single stranded DNA virus, which has been discovered in the serum of a patient with posttransfusion hepatitis of unknown etiology. TTV is widespread in the population, however, the mode of its transmission is unclear. This study was conducted to search for TTV-DNA positivity rates and its relationship with the clinical outcomes of recipients who underwent multiple blood or blood product transfusion, together with healthy children. TTV-DNA was investigated in 52 multitransfused pediatric patients (age range: 3 mnths - 17.5 yrs, mean age: 9.2 +/- 5.7 years) and 18 healthy children (age range: 1 mnth - 16.5 yrs, mean age: 8.1 +/- 4.9 years), by qualitative in-house semi-nested polymerase chain reaction (PCR) with the primers NG059, NG061 and NG063, generated from ORF1 region of the viral genome. TTV-DNA was found positive in 30.8% of multitransfused, and 16.7% of healthy children. The differences of TTV-DNA positivity rates between the multitransfused and control groups, and ALT values between the patients with positive and negative TTV-DNA, were statistically insignificant (p>0.05). As a result, no relationship was detected between TTV positivity and hepatitis, although there was a statistically insignificant increase of TTV-DNA positivity in multitransfused children. However, since the primers of ORF1 N22 region used in our PCR method did not have enough sensitivity for the detection of TTV-DNA, it has been concluded that more sensitive primers such as UTR primers, should be used for more reliable evaluation of the results.
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PMID:[Investigation of TT virus-DNA in multitransfused children and healthy children]. 1590 Aug 38

Consensus covariation-based secondary structural models for the 5' 140 nucleotides of the 5' untranslated regions (5'UTRs) from mouse hepatitis virus (MHV) and severe acute respiratory syndrome coronavirus (SCoV) were developed and predicted three major helical stem-loop structures, designated stem-loop 1 (SL1), SL2, and SL4. The SCoV 5'UTR was predicted to contain a fourth stem-loop, named SL3, in which the leader transcriptional regulatory sequence (TRS) is folded into a hairpin loop. cDNAs corresponding to MHV/SCoV chimeric genomes were constructed by replacing the complete MHV 5'UTR with the corresponding SCoV sequence and by separately replacing MHV 5'UTR putative SL1, putative SL2, TRS, and putative SL4 with the corresponding SCoV sequences. Chimeric genomes were transcribed in vitro, and viruses were recovered after electroporation into permissive cells. Genomes in which the MHV 5'UTR SL1, SL2, and SL4 were individually replaced by their SCoV counterparts were viable. Chimeras containing the complete SCoV 5'UTR or the predicted SCoV SL3 were not viable. A chimera containing the SCoV 5'UTR in which the SCoV TRS was replaced with the MHV TRS was also not viable. The chimera containing the entire SCoV 5'UTR failed to direct the synthesis of any virus-specific RNA. Replacing the SCoV TRS with the MHV TRS in the MHV/5'UTR SCoV chimera permitted the synthesis of minus-sense genome-sized RNA but did not support the production of positive- or minus-sense subgenomic RNA7. A similar phenotype was obtained with the MHV/SCoV SL3 chimera. These results suggest a role for the TRS in the replication of minus-sense genomic RNA in addition to its known function in subgenomic RNA synthesis.
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PMID:Putative cis-acting stem-loops in the 5' untranslated region of the severe acute respiratory syndrome coronavirus can substitute for their mouse hepatitis virus counterparts. 1692 Aug 22

The genome sequences of three duck hepatitis virus type 1 (DHV-1) strains were determined. Comparative sequence analyses showed that they possessed a typical picornavirus genome organization apart from the unique possession of three in-tandem 2A genes. The 2A1 protein of DHV-1 is an aphthovirus-like 2A protein; the 2A2 protein is not related to any known picornavirus protein; the 2A3 protein is a human parechovirus-like 2A protein. Several other features were found to be unique to the DHV-1 genome when compared with other picornaviruses: (i) the 3' UTR of DHV-1 was composed of 314 nt, the largest among the picornaviruses; (ii) pair-wise amino acid sequence identities between polyprotein of DHV-1 and other picornaviruses are all less than 30%. The pair-wise amino acid sequence identities in the 3D region of DHV-1 with LV and HPeV-1 is only 38.6 and 36.6%, respectively, and less than 30% with all other picornaviruses; (iii) the DHV-1 capsid polypeptide VP0 is not proteolytically cleaved into VP4 and VP2; and (iv) phylogenetic and evolutionary analysis of DHV-1 reveals a new picornavirus clade. It is therefore proposed that DHV-1 should be assigned to a new genus in the Picornaviridae.
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PMID:Molecular analysis of duck hepatitis virus type 1 indicates that it should be assigned to a new genus. 1706 12

The 3' cis-acting element for mouse hepatitis virus (MHV) RNA synthesis resides entirely within the 301-nucleotide 3' untranslated region (3' UTR) of the viral genome and consists of three regions. Encompassing the upstream end of the 3' UTR are a bulged stem-loop and an overlapping RNA pseudoknot, both of which are essential to MHV and common to all group 2 coronaviruses. At the downstream end of the genome is the minimal signal for initiation of negative-strand RNA synthesis. Between these two ends is a hypervariable region (HVR) that is only poorly conserved between MHV and other group 2 coronaviruses. Paradoxically, buried within the HVR is an octanucleotide motif (oct), 5'-GGAAGAGC-3', which is almost universally conserved in coronaviruses and is therefore assumed to have a critical biological function. We conducted an extensive mutational analysis of the HVR. Surprisingly, this region tolerated numerous deletions, rearrangements, and point mutations. Most striking, a mutant deleted of the entire HVR was only minimally impaired in tissue culture relative to the wild type. By contrast, the HVR deletion mutant was highly attenuated in mice, causing no signs of clinical disease and minimal weight loss compared to wild-type virus. Correspondingly, replication of the HVR deletion mutant in the brains of mice was greatly reduced compared to that of the wild type. Our results show that neither the HVR nor oct is essential for the basic mechanism of MHV RNA synthesis in tissue culture. However, the HVR appears to play a significant role in viral pathogenesis.
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PMID:A hypervariable region within the 3' cis-acting element of the murine coronavirus genome is nonessential for RNA synthesis but affects pathogenesis. 1709 94

Differences between the translation efficiencies mediated by the 5'-untranslated regions (5'-UTR) of genotypes (gt) 1 and 3 of hepatitis C virus (HCV) have been reported but it is unknown if such differences are biologically significant. The 5'-UTR was sequenced from paired serum and liver samples from 26 patients with chronic HCV hepatitis (11 gt 1a, 15 gt 3a). To determine whether there is a consistent difference between gts 1a and 3a translation efficiency, 5'-UTR (nt 1-356) and 5'-UTR plus core (nt 1-914) sequences were cloned into bicistronic, luciferase-encoding constructs and relative translation efficiencies (RTE) measured in Huh7 cells and BHK cells. The relationships between viral load, liver biopsy Ishak scores, degree of steatosis and translational activity of the patient-derived nucleotide sequence were examined. There were no differences in 5'-UTR sequence between serum and corresponding liver samples. The mean RTE of 5'-UTR sequences from gt 3a isolates was not significantly different from gt 1a whether or not the core encoding sequence was included, although inclusion of core led to a reduction in RTE by 93-97% for both genotypes. No correlation was found between RTE and serum HCV RNA levels, liver steatosis, inflammation, or fibrosis. However, a significant correlation was found between the presence of steatosis and infection with HCV gt 3a. It is concluded that there was no difference in translation efficiencies of 5'-UTRs from patients infected with gts 1a and 3a, and translation activity measured in vitro does not correlate with viral load or severity of liver disease.
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PMID:Translation efficiencies of the 5'-untranslated region of genotypes 1a and 3a in hepatitis C infected patients. 1724 19

Duck hepatitis strains 90D and 04G were determined to be antigenically unrelated to type 1 duck hepatitis virus (DHV-1) by in vitro cross-neutralization assay. The genome sequences of 90D and 04G revealed that both strains of the new serotype DHV (N-DHV) possessed a typical picornavirus genome organization apart from the unique possession of three in-tandem 2A genes present in DHV-1. The 2A1, 2A2, and 2A3 proteins represented an aphthovirus-like 2A protein, AIG1-like protein, and human parechovirus-like 2A protein, respectively. The N-DHV genome displayed unique features, compared to the DHV-1 genome. The 366 nt 3'UTR of N-DHV, the largest determined thus far among picornaviruses, was 52 nt longer than DHV-1. The pairwise percent identity of the nucleic acid and amino acid sequences at 1D region of N-DHV and DHV-1 were only 69.1-69.7 and 70.1-70.5%, respectively. Finally, phylogenetic and evolutionary analysis of N-DHV revealed that the N-DHV and DHV-1 belong to two different clusters of a novel genus in the Picornaviridae family.
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PMID:Molecular characterization of a new serotype of duck hepatitis virus. 1729 92

Many viral mRNAs contain a 5'-UTR RNA element called internal ribosome-entry site (IRES), which bypasses the requirement of some canonical initiation factors allowing cap-independent translation. The IRES of hepatitis-C virus drives translation by directly recruiting 40S ribosomal subunits and binds to eIF3 which plays a critical role in both cap-dependent and cap-independent translation. However, the molecular basis for eIF3 activity in either case remains enigmatic. Here we report that subunit b of the eIF3 complex directly binds to HCV IRES domain III via its N-terminal-RRM. Because eIF3b was previously shown to be involved in eIF3j binding, biological implications are discussed.
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PMID:Human initiation factor eIF3 subunit b interacts with HCV IRES RNA through its N-terminal RNA recognition motif. 1905 1

Up to today no work has evaluated yet the importance of parameters such Body Mass Index (BMI), cholesterol, triglycerides (TGC) and hepatic percentage of steatosis in the response to therapy with Pegylated Interferon Alfa-2a and Ribavirin in patients with recurrent hepatitis C (genotype 1). 30 consecutive prospectively followed patients diagnosed with recurrent HCV were considered candidates for antiviral therapy. Qualitative and quantitative detection of HCV-RNA was performed with the Cobas Amplicor Hepatitis C Virus Test, version 2.0 and the Cobas Amplicor HCV Monitor, version 2.0 (Roche Diagnostics, Branchburgh, NJ, U.S.A.). HCV genotyping was performed by sequencing of the 5 untraslated region (5' UTR) (Visible Genetics TruGene Hepatitis Assay, Toronto, Canada). The observed distribution of BMI, cholesterol, TGC and steatosis were confirmed to be normally distributed by the one-sample Kolmogorov-Smirnov Goodness of fit test procedure. Comparison of BMI, cholesterol, TGC and steatosis between non responders (NR), sustained virological responders (SVR) and sustained biochemical responders (SBR) groups were analyzed by ANOVA with a post hoc Bonferroni test and correlation between variables was tested by Pearson test. The multivariate analysis was performed to estimate the chance of response on basis of the above mentioned variables. In patients with abnormal results in at least two out of four considered variables the chance of no-response was 40 times higher than that of SBR and 96 times than that of SVR. We can conclude how the management of dismetabolism, diet and exercise therapy can improve BMI, liver histology and, therefore, the response to PEG-IFN Alfa-2a and Ribavirin.
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PMID:Influence of body mass index, cholesterol, triglycerides and steatosis on pegylated interferon alfa-2a and ribavirin treatment for recurrent hepatitis C in patients transplanted for HCV and alcoholic cirrhosis. 1957 29


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