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Query: UMLS:C0019158 (hepatitis)
 30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Genes 4 and 5 of mouse hepatitis virus (MHV) are known to encode nonstructural proteins ns4, ns5a, and ns5b, whose function is unknown. In this study, we demonstrated that one of the MHV strains, MHV-S, did not synthesize mRNA 4 and made a smaller mRNA 5. Sequence analysis showed that the transcription initiation site for gene 4 of MHV-S was mutated from the consensus UCUAAAC to UUUAAAC, consistent with the idea that mutations in this region abolish mRNA synthesis. Furthermore, within gene 5 there were deletions totaling 307 nucleotides which deleted almost all of open reading frame 5a, but preserved open reading frame 5b of gene 5. Comparison of the growth of MHV-S with other MHV strains in DBT cells revealed no significant growth defect in MHV-S. These results suggest that ns4 and ns5a are not essential for viral replication in tissue culture cells, and thus join gene 2 and the hemagglutinin-esterase (HE) gene as nonessential viral genes in MHV.
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PMID:Mouse hepatitis virus S RNA sequence reveals that nonstructural proteins ns4 and ns5a are not essential for murine coronavirus replication. 165 56

We have inserted heterologous genetic material into the nonessential gene 4 of the coronavirus mouse hepatitis virus (MHV) in order to test the applicability of targeted RNA recombination for site-directed mutagenesis of the MHV genome upstream of the nucleocapsid (N) gene and to develop further genetic tools for site-directed mutagenesis of structural genes other than N. Initially, a 19-nucleotide tag was inserted into the start of gene 4a of MHV strain A59 with the N gene deletion mutant Alb4 as the recipient virus. In further work, the entire gene for the green fluorescent protein (GFP) was inserted in place of gene 4, creating the currently largest known RNA virus. The expression of GFP was demonstrated by Western blot analysis of infected cell lysates; however, the level of GFP expression was not sufficient to allow detection of fluorescence of viral plaques. Northern blot analysis of transcripts of GFP recombinants showed the expected alteration of the pattern of the nested MHV subgenomic mRNAs. Surprisingly, though, GFP recombinants also produced an RNA species that was the same size as wild-type mRNA4. Analysis of the 5' end of this species revealed that it was actually a collection of mRNAs originating from 10 different genomic fusion sites, none possessing a canonical intergenic sequence. The finding of these aberrant mRNAs suggests that long-range RNA or the ribonucleoprotein structure of the MHV genome can sometimes be the sole determinant of the site of initiation of transcription.
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PMID:Analysis of a recombinant mouse hepatitis virus expressing a foreign gene reveals a novel aspect of coronavirus transcription. 918 82

The genome of the coronavirus mouse hepatitis virus (MHV) contains genes which have been shown to be nonessential for viral replication and which could, in principle, be used as sites for the introduction of foreign sequences. We have inserted heterologous genetic material into gene 4 of MHV in order (i) to test the applicability of targeted RNA recombination for site-directed mutagenesis of the MHV genome upstream of the N gene; (ii) to develop further genetic tools for mutagenesis of structural genes other than N; and (iii) to examine the feasibility of using MHV as an expression vector. A DI-like donor RNA vector containing the MHV S gene and all genes distal to S was constructed. Initially, a derivative of this was used to insert a 19-nucleotide tag into the start of ORF 4a of MHV-A59 using the N gene deletion mutant A1b4 as the recipient virus. Subsequently, the entire gene for the green fluorescent protein (GFP) was inserted in place of gene 4. This heterologous gene was shown to be expressed by recombinant viruses but not at levels sufficient to allow detection of fluorescence of viral plaques. Northern blot analysis of transcripts of GFP recombinants showed the expected displacement of the mobility, relative to those of wild-type, of all subgenomic mRNAs larger than mRNA5. An unexpected result of the Northern analysis was the observation that GFP recombinants also produced an RNA species the same size as that of wild-type mRNA4. RT-PCR analysis of the 5' end of this species revealed that it was actually a collection of mRNAs originating from a cluster of 10 different sites, none of which possessed a canonical intergenic sequence. The finding of these aberrant mRNAs, all of nearly the same size as wild-type mRNA4, suggests that long range structure of the MHV genome can sometimes be the sole determinant of the site of initiation of transcription.
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PMID:Construction of a mouse hepatitis virus recombinant expressing a foreign gene. 978 95

The protein encoded by ORF 4 of mouse hepatitis virus (MHV) is not required for growth of some strains in tissue culture cells, but its role in pathogenesis in the murine host has not been defined previously in a controlled manner. MHV strain JHM causes acute and chronic neurological diseases in susceptible strains of rodents. To genetically manipulate the structural proteins of this and other strains of MHV, we have generalized an interspecies-targeted RNA recombination selection that was originally developed for the A59 strain of MHV. Using this approach, a recombinant MHV-JHM was constructed in which gene 4 was genetically inactivated. Virus lacking gene 4 expression replicated in tissue culture cells with similar kinetics to recombinant virus in which gene 4 expression was not disrupted. Both types of viruses exhibited similar virulence when analyzed in a murine model of encephalitis. These results establish a targeted recombination system for inserting mutations into MHV-JHM. Furthermore, the protein encoded by ORF 4 is not essential for growth in tissue culture cells or in the CNS of the infected host.
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PMID:Inactivation of expression of gene 4 of mouse hepatitis virus strain JHM does not affect virulence in the murine CNS. 1168 46

Targeted recombination was used to select mouse hepatitis virus isolates with stable and efficient expression of the gene encoding the enhanced green fluorescent protein (EGFP). The EGFP gene was inserted into the murine coronavirus genome in place of the nonessential gene 4. These viruses expressed the EGFP gene from an mRNA of slightly slower electrophoretic mobility than mRNA 4. EGFP protein was detected on a Western blot of infected cell lysates and EGFP activity (fluorescence) was visualized by microscopy in infected cells and in viral plaques. Expression of EGFP remained stable through at least six passages in tissue culture and during acute infection in the mouse central nervous system. These viruses replicated with similar kinetics and to similar final extents as wild-type virus both in tissue culture and in the mouse central nervous system (CNS). They caused encephalitis and demyelination in animals as wild-type virus; however, they were somewhat attenuated in virulence. Isogenic EGFP-expressing viruses that differ only in the spike gene and express either the spike gene of the highly neurovirulent MHV-4 strain or the more weakly neurovirulent MHV-A59 strain were compared; the difference in virulence and patterns of spread of viral antigen reflected the differences between parental viruses expressing each of these spike genes. Thus, EGFP-expressing viruses will be useful in the studies of murine coronavirus pathogenesis in mice.
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PMID:Enhanced green fluorescent protein expression may be used to monitor murine coronavirus spread in vitro and in the mouse central nervous system. 1240 64

Oncogenes are mutated form of normal cellular genes called as proto-oncogenes and conduce to the cancer development process. Despite the fact that so many genes have been described, new genes with oncogenic characteristic and potential or tumor supressoring activity are still being defined. Recently, Up-regulated gene 4/Upregulator of cell proliferation (URG4/URGCP), a novel gene, induced by hepatitis-Bvirus-encoded X antigen (HBxAg), has been identified. URG4/URGCP gene was registered to the National Center for Biotechnology Information-GenBank (NCBI-GenBank, Entrez GeneID: 55665 and Entrez Nucleotide ID NM_017920). URG4/URGCP is located on the short arm of chromosome 7 (7p13) and synthesizes a protein containing 922 amino acids in the cytoplas. Relationship between URG4/URGCP expression and clinicopathologic characteristics were evaluated and significant results were in various cancer types such as hepatocellular carcinoma, osteosarcoma, nasopharyngeal carcinoma, bladder cancer, gastric cancer and glioma. Although, biological activity of URG4/URGCP and its effect mechanism in malignant cells is not fully understood, all interesting and promising results shows that URG4/URGCP may be a putative oncogene that contributes to multistep carcinogenesis, cell cycle regulation and other important biological process in the cell.
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PMID:A novel oncogene URG4/URGCP and its role in cancer. 2977 49