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 hemagglutinin-esterase (HE) membrane glycoprotein is present only in some members of the coronavirus family, including some strains of mouse hepatitis virus (MHV). In the JHM strain of MHV, expression of the HE gene is variable and corresponds to the number of copies of a UCUAA pentanucleotide sequence present at the 3'-end of the leader RNA. This copy number varies among MHV strains, depending on their passage history. The JHM isolates with two copies of UCUAA in their leader RNA showed a high level of HE expression, whereas the JHM isolate with three copies had a low-level expression. In this study, the analysis of HE gene expression was extended to other MHV strains. The synthesis of HE mRNA in these viruses also correlates with the copy number of UCUAA in the leader RNA and the particular intergenic sequence preceding the HE gene. In one MHV strain, MHV-1, no detectable HE mRNA was synthesized, despite the presence of a proper transcription initiation signal. This lack of HE mRNA expression was consistent with a leader RNA containing three UCUAA copies. However, mutations and deletions within the coding region of the MHV-1 HE gene have generated a stretch of sequence which resembled the transcriptional initiation motif, and was shown to initiate the synthesis of a novel smaller mRNA. These findings strengthened the theory that interactions between leader RNA and transcriptional initiation sequences regulate MHV subgenomic mRNA transcription. Sequence analysis revealed that most MHV strains, through extensive mutations, deletions, or insertions, have lost the complete HE open reading frame, thus turning HE into a pseudogene. This high degree of variation is unusual as the other three structural proteins (spike, membrane, and nucleocapsid) are well-maintained. In contrast to bovine coronavirus, which apparently requires HE for viral replication, the HE protein in MHV may be only an accessory protein which is not necessary for viral replication. JHM and MHV-S, however, have preserved the expression of HE protein.
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PMID:Heterogeneity of gene expression of the hemagglutinin-esterase (HE) protein of murine coronaviruses. 164 5

Susceptibility to autoimmune hepatitis is associated with the HLA-DR3 and DR4 haplotypes, but which genes are directly involved in the pathogenesis, has not been established. Low levels of complement component C4 and elevated frequencies of C4 null allotypes have been described in patients, suggesting that the C4 genes, which are closely linked with the HLA loci, may play a role. We therefore examined restriction fragment length polymorphisms in the C4 and 21-hydroxylase genes, and determined HLA-A and B phenotypes, and HLA-DR, DQ and DP genotypes in a large series of Caucasoid patients with autoimmune hepatitis and matched controls. A DNA deletion of the C4A gene and the 21-hydroxylase A pseudogene was found to be present in 50% of patients compared to 23% of controls (Pc < 0.005, relative risk = 3.3). This increase, however, appears to be due to linkage disequilibrium with HLA-DR52a which was most strongly associated with the disease. Complete C4A deficiency, determined by homozygosity for the deletion increased the risk to 18.1 (16% versus 1%, Pc < 0.005), suggesting an additional role for C4 in disease susceptibility. C4 deletions were associated with an increased mortality and tendency to relapse whilst on treatment but did not correlate with age of onset of disease. Our data suggest that MHC-encoded susceptibility to autoimmune hepatitis is polygenic, involving the HLA-DR genes plus other loci, and C4 deficiency may be a marker of disease susceptibility and/or severity.
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PMID:Polymorphism in the human complement C4 genes and genetic susceptibility to autoimmune hepatitis. 785 9

Interferon-alpha (IFN-alpha) is a key element in the defense against viral infection because, in addition to a direct antiviral effect, it exhibits potent immunostimulatory activity. To investigate the function of this cytokine in the woodchuck model of chronic hepatitis B, the woodchuck IFN-alpha gene (IFNA) family was cloned and examined. The data indicate that this is a multigenic family from which 12 IFNA functional sequences and four pseudogene sequences were isolated. The overall identity of the amino acid sequence among the members of the woodchuck IFN-alpha family is 85%, and the identity with the IFN-alpha family from other species such as mice and humans is 50%. The analysis of hepatic expression of IFNA genes showed that wIFNA5a was the subtype transcribed preferentially in the woodchuck liver. The wIFNA genes transcribed in the liver were tested in an eukaryotic expression system and were found to enhance 2-5-oligoadenylate synthetase (2-5-OAS) mRNA levels and to posses a potent antiviral activity. Cloning of woodchuck IFNA genes will allow testing diverse forms of IFN-alpha delivery as well as different combination therapies in woodchuck hepatitis virus infection, thus providing useful information for the design of new strategies for the treatment of patients with chronic hepatitis B.
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PMID:The woodchuck interferon-alpha system: Cloning, family description, and biologic activity. 1222 32

We report here investigation into the genetic basis of mouse hepatitis virus strain 1 (MHV-1) pneumovirulence. Sequencing of the 3' one-third of the MHV-1 genome demonstrated that the genetic organization of MHV-1 was similar to that of other strains of MHV. The hemagglutinin esterase (HE) protein was truncated, and reverse transcription-PCR (RT-PCR) studies confirmed previous work that suggested that the MHV-1 HE is a pseudogene. Targeted recombination was used to select chimeric viruses containing either the MHV-1 S gene or genes encoding all of the MHV-1 structural proteins, on an MHV-A59 background. Challenge studies in mice demonstrated that expression of the MHV-1 S gene within the MHV-A59 background (rA59/S(MHV-1)) increased the pneumovirulence of MHV-A59, and mice infected with this recombinant virus developed pulmonary lesions that were similar to those observed with MHV-1, although rA59/S(MHV-1) was significantly less virulent. Chimeras containing all of the MHV-1 structural genes on an MHV-A59 background were able to reproduce the severe acute respiratory syndrome (SARS)-like pathology observed with MHV-1 and reproducibly increased pneumovirulence relative to rA59/S(MHV-1), but were still much less virulent than MHV-1. These data suggest that important determinants of pneumopathogenicity are contained within the 3' one-third of the MHV-1 genome, but additional important virulence factors must be encoded in the genome upstream of the S gene. The severity of the pulmonary lesions observed correlates better with elevated levels of inflammatory cytokines than with viral replication in the lungs, suggesting that pulmonary disease has an important immunological component.
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PMID:Genetic determinants of mouse hepatitis virus strain 1 pneumovirulence. 2063 Nov 37