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)

Human hepatocyte growth factor (hHGF) was purified from the plasma of six patients with fulminant hepatic failure due to hepatitis B in two and non-A, non-B hepatitis in four. The purified hHGF from each patient contained two major protein bands having molecular weights of 79,000 and 86,000 and several minor bands having molecular weights between 76,000 and 92,000 on sodium dodecyl sulfate-polyacrylamide gel electrophoresis performed under nonreduced conditions. After reduction with 2-mercaptoethanol, three major bands having molecular weights of 58,000, 34,500, and 31,500 were evident. In addition, a band having a molecular weight of 21,000 was detected. hHGF activity was destroyed by its reduction. The hHGF purified from patients demonstrated a dose response in terms of an increase in DNA synthesis using cultured hepatocytes. The hHGF concentration in the plasma of the patients with grade III-IV hepatic coma was calculated to be in the range of 1.8-3.0 nM. Finally the heavy chain of hHGF was not recognized by an anti-human albumin antibody, indicating that hHGF is not biliprotein, an albumin-bilirubin complex, that has been reported to be a putative liver growth factor.
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PMID:Human hepatocyte growth factor in blood of patients with fulminant hepatic failure. Basic aspects. 182 62

Each immunoglobulin G (IgG) subclass has unique physicochemical properties and, probably, unique functions. Each heavy chain is coded by a separate gene on chromosome 14. Deficient synthesis of a subclass may be associated with recurrent or chronic infections, the deficiency not being detected by measurements of levels of total serum IgG. Measurement of levels of IgG subclasses should be part of the work-up of patients who have frequent infections but have normal levels of major immunoglobulin classes. Deficiencies of IgA or IgE frequently coexist with deficiencies of IgG2 or IgG4. Patients with a subclass deficiency often benefit from replacement therapy with intramuscular or intravenous IgG or plasma from a donor free of hepatitis and HTLV-III viruses. It may be critical to provide IgG or plasma that is a good source of the missing immunoglobulin class or subclass. Sometimes it is necessary to administer a product with antibodies to the virus or bacteria responsible for a particular infection.
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PMID:IgG subclass composition of intravenous immunoglobulin preparations: clinical relevance. 309 5

Woodchuck hepatitis virus (WHV), similar to human hepatitis B virus, causes acute liver inflammation that can progress to chronic hepatitis and hepatocellular carcinoma. WHV also invades cells of the host lymphatic system, where it persists for life. We report here that acute and chronic hepadnavirus hepatitis is characterized by a profound difference in the expression of class I major histocompatibility complex (MHC) molecules on the surface of infected hepatocytes and, notably, lymphoid cells. While acute WHV infection is accompanied by the enhanced hepatocyte surface presentation of class I MHC antigen and upregulated transcription of the relevant hepatic genes, inhibition of class I antigen display on liver cells is a uniform hallmark of chronic WHV infection. This inhibition in chronic hepatitis occurs despite augmented (as in acute infection) expression of hepatic genes for class I MHC heavy chain, beta(2)-microglobulin, and transporters associated with antigen processing (TAP1 and TAP2). Further, the class I antigen inhibition is not related to the histological severity of hepatocellular injury, the extent of lymphocytic infiltrations, the level of intrahepatic gamma interferon induction, or the hepatic WHV load. Importantly, the antigen expression is also inhibited on organ lymphoid cells of chronically infected hosts. The results obtained in this study demonstrate that the defective presentation of class I MHC molecules on cells supporting persistent WHV replication is due to viral posttranscriptional interference. This event may diminish the susceptibility of infected hepatocytes to virus-specific T-cell-mediated elimination, hinder virus clearance, and deregulate the class I MHC-dependent functions of the host immune system. This multifarious effect could be critical for perpetuation of liver damage and evasion of the antiviral immunological surveillance in chronic infection and therefore could be supportive of hepadnavirus persistence.
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PMID:Posttranscriptional inhibition of class I major histocompatibility complex presentation on hepatocytes and lymphoid cells in chronic woodchuck hepatitis virus infection. 1077 84

Gamma interferon (IFN-gamma) is an important mediator with multiple functions in the host defense against viral infection. IFN-gamma, in concert with tumor necrosis factor alpha (TNF-alpha), leads to a remarkable reduction of intrahepatic replication intermediates and specific mRNAs of hepatitis B virus (HBV) by a noncytolytic mechanism in the transgenic mouse model. Thus, it is rational to evaluate the potential value of IFN-gamma for the treatment of chronic HBV infection. In the present study, we expressed recombinant woodchuck IFN-gamma (wIFN-gamma) in Escherichia coli and mammalian cells. wIFN-gamma protected woodchuck cells against infection of murine encephalomyocarditis virus in a species-specific manner. It upregulated the mRNA level of the woodchuck major histocompatibility complex class I (MHC-I) heavy chain in permanent woodchuck WH12/6 cells and regulated differentially the gene expression. However, the level of the replication intermediates and specific RNAs of woodchuck hepatitis virus (WHV) in persistently WHV-infected primary woodchuck hepatocytes did not change despite a treatment with 1,000 U of wIFN-gamma per ml or with a combination of wIFN-gamma and woodchuck TNF-alpha. Rather, hepatocytes derived from chronic carriers had an elevated level of the MHC-I heavy-chain mRNAs, most probably due to the exposure to inflammatory cytokines in vivo. Treatment with high doses of wIFN-gamma led to an abnormal cell morphology and loss of hepatocytes. Thus, wIFN-gamma regulates the gene expression in woodchuck hepatocytes but could not deplete WHV replication intermediates and mRNAs in persistently infected hepatocytes. The cellular response to wIFN-gamma may be changed in hepatocytes from chronically WHV-infected woodchucks. It should be clarified in the future whether the continuous exposure of hepatocytes to inflammatory cytokines or the presence of viral proteins leads to changes of the cellular response to wIFN-gamma.
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PMID:Woodchuck gamma interferon upregulates major histocompatibility complex class I transcription but is unable to deplete woodchuck hepatitis virus replication intermediates and RNAs in persistently infected woodchuck primary hepatocytes. 1173 71

Hepatitis B virus (HBV) is one of the main pathogens of hepatitis and hepatocarcinoma. Human plasma-derived antibody to HBV is being used as a prophylactic for postexposure to HBV and liver transplantation currently. However, it is required to replace the plasma-derived anti-HBs antibody (Ab) to a recombinant antibody because of limited availability of human plasma with high anti-HBs Ab titer and possible contamination of human pathogens. We constructed an anti-HBs Ab-enriched phage-display library from peripheral blood B cells of vaccinated volunteers and the size of library was approximately 1.0 x 10(7). The library was panned against hepatitis B surface antigen (HBsAg) and five different clones were isolated. All five clones exhibited the same heavy chain sequence; in contrast, light-chain exhibited one lambda and four different kappa sequences. The Fabs were expressed soluble in E. coli and exhibited affinities of 2.1 x 10(8) approximately 7.7 x 10(8) M(-1).
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PMID:Selection and characterization of human antibodies against hepatitis B virus surface antigen (HBsAg) by phage-display. 1247 Apr 82

The rhesus macaque ( Macaca mulatta) has become a popular animal model for several human infectious diseases, such as HIV (modeled by SIV infection), hepatitis, and malaria. Investigation of T-cell responses in experimental infectious diseases in rhesus macaques has benefited from an expanding understanding of the diversity of macaque MHC class I heavy chains and the restriction of antigen presentation by macaque class I molecules. Here we add to this understanding with the first nucleotide sequences of M. mulatta beta(2)-microglobulin (beta(2)m) mRNA, including a portion of the 3'-untranslated region (3'UTR). In pairwise comparison, the beta(2)m protein of M. mulatta differs from human and chimpanzee beta(2)m by nine amino-acid substitutions (92% identity), and from Macaca fascicularis by one amino-acid difference in the signal peptide region (99% identity). Allelic variations were identified at one site in the 3'UTR. A structural analysis of human or chimpanzee beta(2)m and M. mulatta beta(2)m suggests that the differences cluster in three solvent-exposed clusters and do not involve contacts with the class I heavy chain. We predict that human and macaque beta(2)m should bind interchangeably with the class I heavy chains of the other species, and show that four M. mulatta class I alleles form cell surface complexes with human beta(2)m. Further, we predict that W6/32 (a monoclonal antibody that recognizes a combined epitope of some class I heavy chains and beta(2)m with a subtle species dependence) should bind similarly human or macaque class I molecules that are bound with beta(2)m of either species, supported by evidence of recognition of both heterologous and homologous complexes of macaque class I heavy chains. Our findings contribute to the growing understanding of rhesus macaque histocompatibility antigens and antigen presentation, and to the phylogeny of beta(2)m in primates.
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PMID:Sequence of beta(2)-microglobulin from rhesus macaque ( Macaca mulatta) includes an allelic variation in the 3'-untranslated region. 1496 20

Presentation of class I major histocompatibility complex (MHC) is severely down-regulated on hepatocytes in chronic hepatitis caused by woodchuck hepatitis virus (WHV). To determine which of the viral proteins mediates class I MHC antigen suppression, cultured normal woodchuck hepatocytes were transfected with the complete WHV genome, sequences encoding individual virus proteins, or whole virus genomes in which transcription of selected proteins was disabled by site-specific mutagenesis. It was found that hepatocyte presentation of class I MHC antigen was significantly inhibited following transfection with complete WHV genome or with viral subgenomic fragments encoding envelope pre-S2 protein or pre-S1 protein, which naturally encompasses pre-S2 amino acid sequence. In contrast, hepatocytes transfected with WHV X gene alone demonstrated a profound enhancement in the class I antigen display, whereas those expressing virus major S protein or nucleocapsid (core) protein were not different from control hepatocytes. Analysis of the mutated WHV sequences confirmed that the envelope pre-S2 protein was responsible for inhibition of the class I MHC antigen display. Interestingly, treatment with recombinant woodchuck gamma interferon (rwIFN-gamma) restored the inhibited presentation of the class I antigen. Moreover, the class I antigen suppression was not associated with down-regulation of hepatocyte genes for class I MHC heavy chain, beta(2)-microglobulin, transporters associated with antigen processing, and proteasome subunits. These findings indicate that the defective presentation of class I MHC antigen on hepatocytes transcribing WHV is a consequence of posttranscriptional suppression exerted by virus pre-S2 protein and that this hindrance can be fully reversed by IFN-gamma.
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PMID:Inhibition by woodchuck hepatitis virus of class I major histocompatibility complex presentation on hepatocytes is mediated by virus envelope pre-S2 protein and can be reversed by treatment with gamma interferon. 1691 4

Human hepatitis delta virus (HDV) is the smallest RNA virus in genome. HDV genome is divided into a viroid-like sequence and a protein-coding sequence which could have originated from different resources and the HDV genome was eventually constituted through RNA recombination. The genome subsequently diversified through accumulation of mutations selected by interactions between the mutated RNA and proteins with host factors to successfully form the infectious virions. Therefore, we propose that the conservation of HDV nucleotide sequence is highly related with its functionality. Genome analysis of known HDV isolates shows that the C-terminal coding sequences of large delta antigen (LDAg) are the highest diversity than other regions of protein-coding sequences but they still retain biological functionality to interact with the heavy chain of clathrin can be selected and maintained. Since viruses interact with many host factors, including escaping the host immune response, how to design a program to predict RNA genome evolution is a great challenging work.
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PMID:Evolution and diversity of the human hepatitis d virus genome. 2020 73

Adeno-associated virus (AAV) has become a vector of choice for the treatment of a variety of genetic diseases that require safe and long-term delivery of a missing protein. Muscle-directed gene transfer for delivery of protective antibodies against AIDS viruses and other pathogens has been used experimentally in mice and monkeys. Here we examined a number of variations to AAV vector design for the ability to produce authentic immunoglobulin G (IgG) molecules. Expression of rhesus IgG from a single single-stranded AAV (ssAAV) vector (one vector approach) was compared to expression from two self-complementary AAV (scAAV) vectors, one for heavy chain and one for light chain (two vector approach). Both the one vector and the two vector approaches yielded considerable levels of expressed full-length IgG. A number of modifications to the ssAAV expression system were then examined for their ability to increase the efficiency of IgG expression. Inclusion of a furin cleavage sequence with a linker peptide just upstream of the 2A self-cleaving sequence from foot-and-mouth disease virus (F2A) increased IgG expression approximately 2 fold. Inclusion of these sequences also helped to ensure a proper sequence at the C-terminal end of the heavy chain. Inclusion of the post-transcriptional regulatory element from woodchuck hepatitis virus (WPRE) further increased IgG expression 1.5-2.0 fold. IgG1 versions of the two rhesus IgGs that were examined consistently expressed better than the IgG2 forms. In contrast to what has been reported for AAV2-mediated expression of other proteins, introduction of capsid mutations Y445F and Y731F did not increase ssAAV1-mediated expression of IgG as determined by transduction experiments in cell culture. Our findings provide a rational basis for AAV vector design for expression of authentic IgG.
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PMID:Recombinant AAV Vectors for Enhanced Expression of Authentic IgG. 2733 22

Hepatitis E virus (HEV), the causative agent of hepatitis E, is an important but incompletely understood pathogen causing high mortality during pregnancy and leading to chronic hepatitis in immunocompromised individuals. The underlying mechanisms leading to hepatic damage remain unknown; however, the humoral immune response is implicated. In this study, immunoglobulin (Ig) heavy chain JH -/- knockout gnotobiotic pigs were generated using CRISPR/Cas9 technology to deplete the B-lymphocyte population, resulting in an inability to generate a humoral immune response to genotype 3 HEV infection. Compared to wild-type gnotobiotic piglets, the frequencies of B lymphocytes in the Ig heavy chain JH -/- knockouts were significantly lower, despite similar levels of other innate and adaptive T-lymphocyte cell populations. The dynamic of acute HEV infection was subsequently determined in heavy chain JH -/- knockout and wild-type gnotobiotic pigs. The data showed that wild-type piglets had higher viral RNA loads in feces and sera compared to the JH -/- knockout pigs, suggesting that the Ig heavy chain JH -/- knockout in pigs actually decreased the level of HEV replication. Both HEV-infected wild-type and JH -/- knockout gnotobiotic piglets developed more pronounced lymphoplasmacytic hepatitis and hepatocellular necrosis lesions than other studies with conventional pigs. The HEV-infected JH -/- knockout pigs also had significantly enlarged livers both grossly and as a ratio of liver/body weight compared to phosphate-buffered saline-inoculated groups. This novel gnotobiotic pig model will aid in future studies into HEV pathogenicity, an aspect which has thus far been difficult to reproduce in the available animal model systems.IMPORTANCE According to the World Health Organization, approximately 20 million HEV infections occur annually, resulting in 3.3 million cases of hepatitis E and >44,000 deaths. The lack of an efficient animal model that can mimic the full-spectrum of infection outcomes hinders our ability to delineate the mechanism of HEV pathogenesis. Here, we successfully generated immunoglobulin heavy chain JH -/- knockout gnotobiotic pigs using CRISPR/Cas9 technology, established a novel JH -/- knockout and wild-type gnotobiotic pig model for HEV, and systematically determined the dynamic of acute HEV infection in gnotobiotic pigs. It was demonstrated that knockout of the Ig heavy chain in pigs decreased the level of HEV replication. Infected wild-type and JH -/- knockout gnotobiotic piglets developed more pronounced HEV-specific lesions than other studies using conventional pigs, and the infected JH -/- knockout pigs had significantly enlarged livers. The availability of this novel model will facilitate future studies of HEV pathogenicity.
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PMID:Infection Dynamics of Hepatitis E Virus in Wild-Type and Immunoglobulin Heavy Chain Knockout JH -/- Gnotobiotic Piglets. 3011 71


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