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 murine coronavirus mouse hepatitis virus gene 1 is expressed as a polyprotein, which is cleaved into multiple proteins posttranslationally. One of the proteins is p28, which represents the amino-terminal portion of the polyprotein and is presumably generated by the activity of an autoproteinase domain of the polyprotein (S. C. Baker, C. K. Shieh, L. H. Soe, M.-F. Chang, D. M. Vannier, and M. M. C. Lai, J. Virol. 63:3693-3699, 1989). In this study, the boundaries and the critical amino acid residues of this putative proteinase domain were characterized by deletion analysis and site-directed mutagenesis. Proteinase activity was monitored by examining the generation of p28 during in vitro translation in rabbit reticulocyte lysates. Deletion analysis defined the proteinase domain to be within the sequences encoded from the 3.6- to 4.4-kb region from the 5' end of the genome. A 0.7-kb region between the substrate (p28) and proteinase domain could be deleted without affecting the proteolytic cleavage. However, a larger deletion (1.6 kb) resulted in the loss of proteinase activity, suggesting the importance of spacing sequences between proteinase and substrate. Computer-assisted analysis of the amino acid sequence of the proteinase domain identified potential catalytic cysteine and histidine residues in a stretch of sequence distantly related to papain-like cysteine proteinases. The role of these putative catalytic residues in the proteinase activity was studied by site-specific mutagenesis. Mutations of Cys-1137 or His-1288 led to a complete loss of proteinase activity, implicating these residues as essential for the catalytic activity. In contrast, most mutations of His-1317 or Cys-1172 had no or only minor effects on proteinase activity. This study establishes that mouse hepatitis virus gene 1 encodes a proteinase domain, in the region from 3.6 to 4.4 kb from the 5' end of the genome, which resembles members of the papain family of cysteine proteinases and that this proteinase domain is responsible for the cleavage of the N-terminal peptide.
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PMID:Identification of the catalytic sites of a papain-like cysteine proteinase of murine coronavirus. 839 68

We clarified the clinical and immunogenetical differences between patients with autoimmune hepatitis (AI-CAH), and patients with type C chronic active hepatitis (C-CAH) and type B chronic active hepatitis (B-CAH) who were positive for autoantibodies and hyperglobulinemia. While histories of blood transfusion, intravenous drug abuse and tattoo were seen frequently in patients with type C-CAH, they were rare in patients with AI-CAH. The severe subjective symptoms including anorexia, lethargy, icterus, high fever and extrahepatic manifestations, and severe abnormality of biochemical data were seen in AI-CAH predominantly. Ongoing or past infection of HCV was seen in only 14% of patients with AI-CAH. HLA-DR4 was the most frequently associated with AI-CAH (89%) and 6 DR4-negative patients were positive for DR2. HLA-DNA typing showed that there was no significant difference in the frequency of DR4-associated Dw-alleles between the patients and controls who were positive for DR4. These findings suggest that the basic amino acid at position 13, which is present only on the DR2 and DR4 B1 molecules (Arg on DR2 and His on DR4), may contribute to the susceptibility to autoimmune hepatitis of Japanese. Thus, we conclude that AI-CAH is a genetically restricted, disease, and different from C-CAH which is a viral infectious disease.
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PMID:Comparison of the clinical and immunogenetic features between patients with autoimmune hepatitis and patients with type C chronic active hepatitis. 848 32

The capsid particle of hepadnaviruses is assembled from its dimer precursors. However, the mechanism of the protein-protein interaction is still poorly understood. A small region in the capsid protein of woodchuck hepatitis virus (WHV) contains four hydrophobic residues, including leucine 101, leucine 108, valine 115, and phenylalanine 122, that are conserved and spaced every seventh residue in the primary sequence to form a hydrophobic heptad repeat (hhr). A hydrophobic force often plays an important role in the interaction of proteins. Therefore, to investigate the role of this region in capsid assembly, we individually changed the codons specifying these four hydrophobic amino acids to codons specifying alanine or proline. In addition, we examined the in vivo infectivity of a WHV genome bearing a naturally occurring single amino acid change (histidine 104-->proline) in the hhr region. The phenotype of each altered genome was determined in both eukaryotic and prokaryotic systems by a capsid protein assay and electron microscopic examination. We show that replacement of any one of the four hydrophobic residues with alanine did not prevent capsid assembly. However, assembled capsid particles were not detected if combinations of any two of the four residues were substituted with alanines or if the spacing of these four hydrophobic residues was changed. An individual introduction of a proline (which dramatically changes the secondary structure of proteins) into different positions of this small region also abolished capsid assembly in vitro or viral replication in vivo. These results suggested that the hhr region of the core protein of WHV was critical for capsid assembly.
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PMID:A hydrophobic heptad repeat of the core protein of woodchuck hepatitis virus is required for capsid assembly. 879 54

The NS3 protein of hepatitis C virus contains a chymotrypsin-like serine proteinase domain. We built a homology model of this domain which predicts the presence of a tetradentate metal binding site formed by three cysteines and one histidine. These residues are strictly conserved in all known hepatitis C viral genotypes as well as in other recently discovered related hepatitis viruses. We show that the hepatitis C virus enzyme does indeed contain a Zn2+ ion with S3N ligation and that the metal is required for structural integrity and activity of the enzyme. Strikingly, the residues forming the metal binding site are also conserved in the chymotrypsin-like 2A cysteine proteinases of picornaviruses. Remarkably, in these highly variable viral genomes the metal binding site is more conserved than the catalytic residues and thus allows us to define a novel class of zinc binding chymotrypsin-like proteinases and to identify a new attractive target for antiviral therapy.
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PMID:A zinc binding site in viral serine proteinases. 887 93

Stevens-Johnson syndrome is a rare immunologic reaction that may involve skin or various mucosal surfaces. The etiology may range from multiple pharmacologic agents to viral infections. Associated findings can range from minimal skin and mucosal involvement to extensive dermal exfoliation, nephritis, lymphadenopathy, hepatitis, and multiple serologic abnormalities. We report a 36 year-old caucasian male who developed a pruritic, raised maculopapular eruption on Day 17 of intravenous vancomycin for treatment of probable bacterial endocarditis. The vancomycin was discontinued. The patient had received a prosthetic aortic valve subsequent to acute rheumatic valve disease 20 years earlier, but had been well until development of endocarditis. The rash became more extensive to involve the torso, abdomen, legs, and arms. His fever persisted, and he developed neutropenia and eosinophilia. Axillary and inguinal lymphadenopathy, pharyngeal irritation, lip swelling, conjunctival injection, and elevated liver function studies also developed following cessation of the vancomycin. Eight days after eruption and fever began, corticosteroid therapy was instituted, with subsequent improvement of symptoms in less than 24 hours. Allergic reactions to vancomycin have included Stevens-Johnson syndrome rarely, and only one other case of adenopathy has been recorded. Most reactions have been in patients with severe renal insufficiency. We believe this patient is the first case of vancomycin-induced Stevens-Johnson syndrome in a previously healthy patient to be complicated by lymphadenopathy, hepatitis, and multiple serologic abnormalities.
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PMID:Vancomycin-induced Stevens-Johnson syndrome. 893 97

We report a 6-week-old boy with meperidine neurotoxicity. What distinguished our patient from those previously reported was his minimal exposure to therapeutic doses of meperidine in the setting of normal renal function, and no history of sickle cell anemia, cancer, hepatitis, or cirrhosis. In addition, our patient had no abnormal changes in the electroencephalogram during the event. After only 2 doses of meperidine, he exhibited acute orofacial dyskinesias consisting of tongue thrusting, lip pursing, and facial grimacing combined with prominent flexion of the arms and stiffening of his legs. However, a normal sucking response remained. His symptoms resolved over the next 36 hours and did not respond to naloxone. We believe that this unique presentation of meperidine-induced neurotoxicity may be due to changes in the basal ganglia resulting from perinatal hypoxemia.
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PMID:Acute neurotoxicity of meperidine in an infant. 896 93

The coronavirus, mouse hepatitis virus strain A59 (MHV), expresses a chymotrypsin-like cysteine proteinase (3CLpro) within the gene 1 polyprotein. The MHV 3CLpro is similar to the picornavirus 3C proteinases in the relative location of confirmed catalytic histidine and cysteine residues and in the predicted use of Q/(S, A, G) dipeptide cleavage sites. However, less is known concerning the participation of aspartic acid or glutamic acid residues in catalysis by the coronavirus 3C-like proteinases or of the precise coding sequence of 3CLpro within the gene 1 polyprotein. In this study, aspartic acid residues in MHV 3CLpro were mutated and the mutant proteinases were tested for activity in an in vitro trans cleavage assay. MHV 3CLpro was not inactivated by substitutions at Asp3386 (D53) or Asp3398 (D65), demonstrating that they were not catalytic residues. MHV 3CLpro was able to cleave at a glutamine-glycine (QG3607-8) dipeptide within the 3CLpro domain upstream from the predicted carboxy-terminal QS3636-6 cleavage site of 3CLpro. The predicted full-length 3CLpro (S3334 to Q3635) had an apparent mass of 27 kDa, identical to the p27 3CLpro in cells, whereas the truncated proteinase (S3334 to Q3607) had an apparent mass of 24 kDa. This 28-amino-acid carboxy-terminal truncation of 3CLpro rendered it inactive in a trans cleavage assay. Thus, MHV 3CLpro was able to cleave at a site within the putative full-length proteinase, but the entire predicted 3CLpro domain was required for activity. These studies suggest that the coronavirus 3CL-proteinases may have a substantially different structure and catalytic mechanism that other 3C-like proteinases.
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PMID:Determinants of mouse hepatitis virus 3C-like proteinase activity. 914 89

The sexual, household and nosocomial transmission of Hepatitis C virus infection were studied in patients with HCV-RNA positive chronic active hepatitis, confirmed by PCR. Liver function tests and hepatitis C virus serology were performed in family members living in the same household of patients, sexual partners as well as members of the hospital environment in the Department of Hepatology. Fifty-three members of 27 families and 32 staff-members were examined. Quantitative HCR-RNA-PCR and virus serotype of anti-HCV (III.gen.) positive individuals were also identified. Two of the family members turned out to be anti-HCV positive. The husband in one of the married couples was treated for hepatitis of unidentified etiology in an Infectology Department four years ago. His wife was found to have chronic hepatitis C since two years. They both had C virus of serotype 1. The mother and daughter in another family suffered from von Willebrand factor deficiency syndrome. It was documented that they were infected by blood transfusion at different occasions. Their C virus serotypes were different. All the staff members of Hepatology Department were anti-HCV negative. These results confirmed the possibility of the non-parenteral transmission of hepatitis C virus, however, its incidence is very low.
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PMID:[How great is the risk of personal contact in the transmission of hepatitis C virus infection?]. 915 37

We previously demonstrated by site-directed mutagenesis analysis that the amino acid residues at positions 62 and 214 to 216 in the N-terminal region of mouse hepatitis virus (MHV) spike (S) protein are important for receptor-binding activity (H. Suzuki and F. Taguchi, J. Virol. 70:2632-2636, 1996). To further identify the residues responsible for the activity, we isolated the mutant viruses that were not neutralized with the soluble form of MHV receptor proteins, since such mutants were expected to have mutations in amino acids responsible for receptor-binding activity. Five soluble-receptor-resistant (srr) mutants isolated had mutations in a single amino acid at three different positions: one was at position 65 (Leu to His) (srr11) in the S1 subunit and three were at position 1114 (Leu to Phe) (srr3, srr4, and srr7) and one was at position 1163 (Cys to Phe) (srr18) in the S2 subunit. The receptor-binding activity examined by a virus overlay protein blot assay and by a coimmunoprecipitation assay showed that srr11 S protein had extremely reduced binding activity, while the srr7 and srr18 proteins had binding activity similar to that of wild-type cl-2 protein. However, when cell surface receptors were used for the binding assay, all srr mutants showed activity similar to that of the wild type or only slightly reduced activity. These results, together with our previous observations, suggest that amino acids located at positions 62 to 65 of S1, a region conserved among the MHV strains examined, are important for receptor-binding activity. We also discuss the mechanism by which srr mutants with a mutation in S2 showed high resistance to neutralization by a soluble receptor, despite their sufficient level of binding to soluble receptors.
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PMID:Identification of spike protein residues of murine coronavirus responsible for receptor-binding activity by use of soluble receptor-resistant mutants. 937 59

A case is reported of a 43-year-old man who presented prostatitis and hepatitis due to Brucella melitensis. His symptoms were icterus, weakness, anorexia, fever, and urinary discomfort. Physical examination revealed icterus and hepatosplenomegaly. Lymphomonocytosis, elevated erythrocyte sedimentation rate and abnormal liver functions had been detected in laboratory tests. Brucella melitensis was isolated from prostatic fluid and blood cultures.
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PMID:Prostatitis and hepatitis due to Brucella melitensis: a case report. 951 79


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