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)

Replication-competent retroviral vectors (pFOV-1 to -3 and -7) were constructed on the basis of an infectious human foamy virus molecular clone which has deletions in the U3 region of the long terminal repeat and in the 3' region of the genome, previously identified to be nonessential for virus replication in vitro. The CAT and luciferase indicator genes were expressed as C-terminal fusion proteins to 215 amino acids of the viral Bet protein in the pFOV-1 vector. Introduction of the foot-and-mouth disease 2A protease sequence between the truncated bet coding sequence and the cloning site for the insertion of foreign genes in the pFOV-7 vector resulted in self-cleaving of the recombinant fusion protein. Alternatively, an internal ribosomal binding site was introduced, allowing expression of authentic foreign protein (pFOV-2 and -3 vectors). DNA fragments derived from the mouse hepatitis virus surface gene up to the length of 1.3 kb were inserted into pFOV-1. The vector constructs gave rise to viruses which were fully infectious in diploid human fibroblasts and recombinant viruses stably expressed high levels of foreign protein indicating that the pFOV vectors may be useful tools to study the effects of proteins of interest at least in tissue culture cells.
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PMID:Replicating foamy virus-based vectors directing high level expression of foreign genes. 779 69

Sequence analysis of duck hepatitis virus type 1 (DHV-1) led to its classification as the only member of a new genus, Avihepatovirus, of the family Picornaviridae, and so was renamed duck hepatitis A virus (DHAV). The 5' untranslated region (5' UTR) plays an important role in translation initiation and RNA synthesis of the picornavirus. Here, we provide evidence that the 651-nucleotide (nt)-long 5' UTR of DHAV genome contains an internal ribosome entry site (IRES) element that functions efficiently in vitro and within BHK cells. Comparative sequence analysis showed that the 3' part of the DHAV 5' UTR is similar to the porcine teschovirus 1 (PTV-1) IRES in sequence and predicted secondary structure. Further mutational analyses of the predicted domain IIId, domain IIIe, and pseudoknot structure at the 3' end of the DHAV IRES support our predicted secondary structure. However, unlike the case for the PTV-1 IRES element, analysis of various deletion mutants demonstrated that the optimally functional DHAV IRES element with a size of approximately 420 nt is larger than that of PTV-1 and contains other peripheral domains (Id and Ie) that do not exist within the type IV IRES elements. The domain Ie, however, could be removed without significant loss of activity. Surprisingly, like the hepatitis A virus (HAV) IRES element, the activity of DHAV IRES could be eliminated by expression of enterovirus 2A protease. These findings indicate that the DHAV IRES shares common features with type IV picornavirus IRES elements, whereas it exhibits significant differences from type IV IRESs. Therefore, we propose that DHAV possesses a distinct type IV IRES element of picornavirus.
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PMID:Duck Hepatitis A virus possesses a distinct type IV internal ribosome entry site element of picornavirus. 2209 Jan 6

Coxsackievirus B3 (CVB3) is a causative agent of viral myocarditis, hepatitis, pancreatitis, and meningitis in humans. The adenosine-uridine (AU)-rich element RNA binding factor 1 (AUF1) is an integral component in the regulation of gene expression. AUF1 destabilizes mRNAs and targets them for degradation by binding to AU-rich elements in the 3' untranslated region (UTR) of mRNAs. The 3'-UTR of the CVB3 genome contains canonical AU-rich sequences, raising the possibility that CVB3 RNA may also be subjected to AUF1-mediated degradation. Here, we reported that CVB3 infection led to cytoplasmic redistribution and cleavage of AUF1. These events are independent of CVB3-induced caspase activation but require viral protein production. Overexpression of viral protease 2A reproduced CVB3-induced cytoplasmic redistribution of AUF1, while in vitro cleavage assay revealed that viral protease 3C contributed to AUF1 cleavage. Furthermore, we showed that knockdown of AUF1 facilitated viral RNA, protein, and progeny production, suggesting an antiviral property for AUF1 against CVB3 infection. Finally, an immunoprecipitation study demonstrated the physical interaction between AUF1 and the 3'-UTR of CVB3, potentially targeting CVB3 genome toward degradation. Together, our results suggest that cleavage of AUF1 may be a strategy employed by CVB3 to enhance the stability of its viral genome.
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PMID:Cytoplasmic redistribution and cleavage of AUF1 during coxsackievirus infection enhance the stability of its viral genome. 2357 32