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)

The dual observations that human leukocyte antigens have an antigen-binding groove and that the polymorphism we study as human leukocyte antigen types is largely related to amino acid substitutions in and around that groove have provided a new focus for immunogenetic studies. In autoimmune liver disease, recent studies have described specific amino acid substitutions in the antigen-binding groove of human leukocyte antigen DR molecules that may determine both disease susceptibility, through their direct influence on antigen binding, and the severity of the disease. In autoimmune hepatitis, lysine residues at DR beta position 71 in European subjects and arginine or histidine residues at DR beta position 13 in Japanese subjects may be responsible for much human leukocyte antigen-encoded disease susceptibility. Similar claims have been made for leucine residues at DR beta 38 in primary sclerosing cholangitis and for leucine residues at DP beta 35 in Japanese patients with primary biliary cirrhosis. To date, our knowledge of genetic susceptibility to autoimmune liver disease is incomplete. Other genes may contribute to susceptibility to autoimmune liver disease--for example the contribution of TAP genes, upstream promoter sequences and class III genes on chromosome 6 and the T-cell receptor genes and complement genes elsewhere in the human genome is currently unclear. Additional information concerning the immunogenetic contribution to disease severity is needed to complete the picture.
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PMID:The molecular genetics of autoimmune liver disease. 802 Aug 93

We aimed to study whether TAP and LMP polymorphisms could influence the severity of liver disease or the response to IFN treatment in patients with chronic HCV infection. TAPZ*0103 gene frequencies in carriers with normal ALT was significantly higher than that in CLD patients. As for the results of IFN responses, LMP7-K gene frequency in sustained-responders was higher than that in non-responders. Multivariate analysis revealed that LMP7-K and HCV RNA quantity were independent factors influencing the outcome of IFN therapy. Furthermore, among patients with a low viral load, the LMP7-K positive patients had a significantly higher ratio of sustained response compared to those without LMP7-K. The TAP2 polymorphism may be closely associated with low hepatitis activity, whereas the LMP7 polymorphism influences the efficacy of IFN treatment and can be a useful predictive parameter in HCV patients with a low viral load.
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PMID:[Involvement of TAP2 and LMP7 gene polymorphisms in HCV infection]. 1149 32

During thymic education, strongly self-reactive T cells are selected against, while weakly self-reactive cells are positively selected. However, the probability of an antigen being self derived and the number of self-peptides have never been properly defined. We merge algorithms for: cleavage prediction, TAP binding probability estimates and MHC binding properties to estimate the number and distribution of all MHC binding peptides. We show that the number of self-peptides with a high affinity to a given human MHC-I molecule is between 200 and almost 200,000 and is much less than the estimated total number of peptide sequences. This result suggests that MHC molecules are selected through evolution in order to reduce the number of self-peptides presented. The number of viral peptides presented is also low and varies between zero and a few hundred per virus for a given HLA allele. These low numbers explain the need for multiple alleles within an individual. We show that six codominantly expressed MHC-I alleles are sufficient to present at least one or two peptides per virus for the vast majority of viruses. Viruses can escape detection either by using peptides that cannot be presented on MHC molecules or by using peptides whose presented segments overlap significantly with self. Most viral families (such as influenza, HIV, Hepatitis and HPV) present as many peptides as predicted from their genome length, and overlap minimally with the human self-peptide repertoire. However, a few latent viruses, such as herpes and adenovirus share considerable peptide sequence homology with their human hosts.
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PMID:T-cell epitope repertoire as predicted from human and viral genomes. 1592 55

Hepatitis delta virus (HDV) is a satellite virus of hepatitis B virus (HBV). HDV genome encodes two forms of hepatitis delta antigen (HDAg), small HDAg (HDAg-S), which is required for viral replication, and large HDAg (HDAg-L), which is essential for viral assembly. HDAg-L is identical to HDAg-S except that it bears a 19-amino acid extension at the C terminus. Both HDAgs contain a nuclear localization signal (NLS), but only HDAg-L contains a CRM1-independent nuclear export signal at its C terminus. The nuclear export activity of HDAg-L is important for HDV particle formation. However, the mechanisms of HDAg-L-mediated nuclear export of HDV ribonucleoprotein are not clear. In this study, the host cellular RNA export complex TAP-Aly was found to form a complex with HDAg-L, but not with an export-defective HDAg-L mutant, in which Pro205 was replaced by Ala. HDAg-L was found to colocalize with TAP and Aly in the nucleus. The C-terminal domain of HDAg-L was shown to directly interact with the N terminus of TAP, whereas an HDAg-L mutant lacking the NLS failed to interact with full-length TAP. In addition, small hairpin RNA-mediated down-regulation of TAP or Aly reduced nuclear export of HDAg-L and assembly of HDV virions. Furthermore, a peptide, TAT-HDAg-L(198-210), containing the 10-amino acid TAT peptide and HDAg-L(198-210), inhibited the interaction between HDAg-L and TAP and blocked HDV virion assembly and secretion. These data demonstrate that formation and release of HDV particles are mediated by TAP and Aly.
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PMID:Cellular Nuclear Export Factors TAP and Aly Are Required for HDAg-L-mediated Assembly of Hepatitis Delta Virus. 2780 29