UMLS:C0019158 - FACTA Search

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

The initial step in mouse hepatitis virus (MHV) RNA replication is the synthesis of negative-strand RNA from a positive-strand genomic RNA template. Our approach to begin studying MHV RNA replication is to identify the cis-acting signals for RNA synthesis and the proteins which recognize these signals at the 3' end of genomic RNA of MHV. To determine whether host cellular and/or viral proteins interact with the 3' end of the coronavirus genome, an RNase T1 protection/gel mobility shift electrophoresis assay was used to examine cytoplasmic extracts from mock- and MHV-JHM-infected 17Cl-1 murine cells for the ability to form complexes with defined regions of the genomic RNA. We demonstrated the specific binding of host cell proteins to multiple sites within the 3' end of MHV-JHM genomic RNA. By using a set of RNA probes with deletions at either the 5' or 3' end or both ends, two distinct binding sites were located. The first protein-binding element was mapped in the 3'-most 42 nucleotides of the genomic RNA [3' (+42) RNA], and the second element was mapped within an 86-nucleotide sequence encompassing nucleotides 171 to 85 from the 3' end of the genome (171-85 RNA). A single potential stem-loop structure is predicted for the 3' (+)42 RNA, and two stem-loop structures are predicted for the 171-85 RNA. Proteins interacting with these two elements were identified by UV-induced covalent cross-linking to labeled RNAs followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis. The RNA-protein complex formed with the 3'-most 42 nucleotides contains approximately five host polypeptides, a highly labeled protein of 120 kDa and four minor species with sizes of 103, 81, 70, and 55 kDa. The second protein-binding element, contained within a probe representing nucleotides 487 to 85 from the 3' end of the genome, also appears to bind five host polypeptides, 142, 120, 100, 55, and 33 kDa in size, with the 120-kDa protein being the most abundant. The RNA-protein complexes observed with MHV-infected cells in both RNase protection/gel mobility shift and UV cross-linking assays were identical to those observed with uninfected cells. The possible involvement of the interaction of host proteins with the viral genome during MHV replication is discussed.
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PMID:Specific binding of host cellular proteins to multiple sites within the 3' end of mouse hepatitis virus genomic RNA. 788 46

Minus-strand RNA is the first RNA species made by plus-strand RNA viruses, such as mouse hepatitis virus (MHV), and serves as a template for subsequent RNA replication and transcription. The regulation of minus-strand RNA synthesis has been difficult to study because of the paucity of minus-strand RNA. We have optimized a ribonuclease (RNase) protection assay which enabled the detection of minus-strand RNA synthesis from nonreplicating RNAs, thus clearly separating minus-strand from plus-strand RNA synthesis. We used an MHV defective interfering (DI) RNA containing a chloramphenicol acetyltransferase gene as a reporter to determine the cis-acting signal for MHV minus-strand RNA synthesis. It was found that minus-strand RNAs existed in double-stranded RNA form in the cell. By using various deletion clones, we demonstrated that the cis-acting signal for minus-strand RNA synthesis resides in the 55 nucleotides from the 3' end plus poly(A) tail of the MHV genome. This is much shorter than the 436 nucleotides previously reported for the 3'-end replication signal. No specific upstream MHV sequence was required for the initiation of minus-strand RNA synthesis. This finding suggests that the requirement for minus-strand RNA synthesis is much less stringent than that for genomic and subgenomic plus-strand RNA synthesis and that some of the minus-strand RNAs made may not be functional since they may lack the recognition signals for RNA replication or transcription. We further showed that the DI clones which actively transcribed a subgenomic mRNA from an internal intergenic sequence synthesized much less minus-strand RNA than those clones which did not transcribe subgenomic mRNAs, indicating that minus-strand RNA synthesis was inhibited by transcription from an internal promoter of the same DI RNA. This result also suggests that the regulation of the quantities of subgenomic mRNAs is not at the point of minus-strand RNA synthesis but rather at plus-strand RNA synthesis. Furthermore, the finding that the leader sequence was not required for minus-strand RNA synthesis suggests that the leader RNA regulates mRNA transcription during plus-strand RNA synthesis.
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PMID:Identification of the cis-acting signal for minus-strand RNA synthesis of a murine coronavirus: implications for the role of minus-strand RNA in RNA replication and transcription. 796 4

To investigate the mechanism by which viruses are cleared from neurons in the central nervous system, we have utilized a mouse model involving infection with a neurotropic variant of mouse hepatitis virus (OBLV60). After intranasal inoculation, OBLV60 grew preferentially in the olfactory bulbs of BALB/c mice. Using in situ hybridization, we found that viral RNA localized primarily in the outer layers of the olfactory bulb, including neurons of the mitral cell layer. Virus was cleared rapidly from the olfactory bulb between 5 and 11 days. Athymic nude mice failed to eliminate the virus, demonstrating a requirement for T lymphocytes. Immunosuppression of normal mice with cyclophosphamide also prevented clearance. Both CD4+ and CD8+ T-cell subsets were important, as depletion of either of these subsets delayed viral clearance. Gliosis and infiltrates of CD4+ and CD8+ cells were detected by immunohistochemical analysis at 6 days. The role of cytokines in clearance was investigated by using an RNase protection assay for interleukin-1 alpha (IL-1 alpha), IL-1 beta, IL-2, IL-3, IL-4, IL-5, IL-6, tumor necrosis factor alpha (TNF-alpha), TNF-beta, and gamma interferon (IFN-gamma). In immunocompetent mice there was upregulation of RNA for IL-1 alpha, IL-1 beta, IL-6, TNF-alpha, and IFN-gamma at the time of clearance. Nude mice had comparable increases in these cytokine messages, with the exception of IFN-gamma. Induction of major histocompatibility complex class I (MHC-I) molecules on cells in infected brains was demonstrated by immunohistochemical analyses in normal and nude mice, suggesting that IFN-gamma may not be necessary for induction of MHC-I on neural cells in vivo.
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PMID:Cytokine induction during T-cell-mediated clearance of mouse hepatitis virus from neurons in vivo. 805 31

Murine coronaviruses such as mouse hepatitis virus (MHV) infect mouse cells via cellular receptors that are isoforms of biliary glycoprotein (Bgp) of the carcinoembryonic antigen gene family (G. S. Dveksler, C. W. Dieffenbach, C. B. Cardellichio, K. McCuaig, M. N. Pensiero, G.-S. Jiang, N. Beauchemin, and K. V. Holmes, J. Virol. 67:1-8, 1993). The Bgp isoforms are generated through alternative splicing of the mouse Bgp1 gene that has two allelic forms called MHVR (or mmCGM1), expressed in MHV-susceptible mouse strains, and mmCGM2, expressed in SJL/J mice, which are resistant to MHV. We here report the cloning and characterization of a new Bgp-related gene designated Bgp2. The Bgp2 cDNA allowed the prediction of a 271-amino-acid glycoprotein with two immunoglobulin domains, a transmembrane, and a putative cytoplasmic tail. There is considerable divergence in the amino acid sequences of the N-terminal domains of the proteins coded by the Bgp1 gene from that of the Bgp2-encoded protein. RNase protection assays and RNA PCR showed that Bgp2 was expressed in BALB/c kidney, colon, and brain tissue, in SJL/J colon and liver tissue, in BALB/c and CD1 spleen tissue, in C3H macrophages, and in mouse rectal carcinoma CMT-93 cells. When Bgp2-transfected hamster cells were challenged with MHV-A59, MHV-JHM, or MHV-3, the Bgp2-encoded protein served as a functional MHV receptor, although with a lower efficiency than that of the MHVR glycoprotein. The Bgp2-mediated virus infection could not be inhibited by monoclonal antibody CC1 that is specific for the N-terminal domain of MHVR. Although CMT-93 cells express both MHVR and Bgp2, infection with the three strains of MHV was blocked by pretreatment with monoclonal antibody CC1, suggesting that MHVR was the only functional receptor in these cells. Thus, a novel murine Bgp gene has been identified that can be coexpressed in inbred mice with the Bgp1 glycoproteins and that can serve as a receptor for MHV strains when expressed in transfected hamster cells.
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PMID:Bgp2, a new member of the carcinoembryonic antigen-related gene family, encodes an alternative receptor for mouse hepatitis viruses. 820 27

A conserved 11-nucleotide sequence, UGAAUGAAGUU, at the 3' end of the genomic RNA of coronavirus mouse hepatitis virus was required for host protein binding and viral RNA synthesis. An RNA probe containing this 11-nucleotide sequence bound four cellular proteins with a highly labeled protein of 120 kDa and three minor species with sizes of 103, 81, and 55 kDa. Mutation of the 11-nucleotide motif abolished cellular protein binding. The RNA-protein complexes observed with cytoplasmic extracts from MHV-JHM-infected cells in both RNase protection/gel mobility shift and UV cross-linking assays were indistinguishable from those observed with extracts from uninfected cells. Both negative-strand synthesis and positive-strand replication of viral defective interfering RNAs in the presence of helper virus were affected by mutations that disrupt RNA-protein complex formation, even though the 11 mutated nucleotides were converted to the wild-type sequence, presumably by recombination with helper virus. Kinetic analysis indicated that recombination between DI RNA and helper virus occurred relatively early in the MHV replicative cycle at 5.5 to 7.5 hr postinfection, a time when viral RNA synthesis and replication of positive-strand DI RNA were at barely detectable levels. A DI RNA with a mutation upstream of the protein binding element replicated as efficiently as wild type without undergoing recombination. Thus, the 11-nucleotide conserved host protein binding motif appears to play an important role in viral RNA replication.
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PMID:A conserved motif at the 3' end of mouse hepatitis virus genomic RNA required for host protein binding and viral RNA replication. 852 8

Antibodies (Abs) hydrolyzing proteins, DNA, and RNA are detected in the blood of patients with various autoimmune diseases. In the present work, homogeneous preparations of IgG Abs from the blood of the healthy donors as well as patients with A, B, C, and delta types of viral hepatitis, influenza, pneumonia, tuberculosis, tonsillitis, duodenal ulcer, and some types of cancer were purified. For the first time, the fraction of IgG and its Fab fragments of patients with viral hepatitis were shown to have high DNA- and RNA-hydrolyzing activity. In case of Abs from the healthy donors and patients with other diseases, high activity of Abs was not detected. The data obtained by various methods indicate that the activity of hepatitis Abs is an intrinsic property of the immunoglobulins. The relative rates of hydrolysis of cCMP, poly(U), poly(A), poly(C), and tRNA(Phe) by hepatitis Abs were compared with those of RNase A and other RNases from human blood. Significant differences in activities of Abs and nucleases in hydrolysis of model substrates were demonstrated. Thus, catalytically active Abs can appear in the blood of patients not only with autoimmune disorders, but with viral diseases as well.
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PMID:DNA- and RNA-hydrolyzing antibodies from the blood of patients with various forms of viral hepatitis. 948 69

Infection of C57BL/6 mice with mouse hepatitis virus strain V5A13.1 (MHV-V5A13.1) results in an acute encephalitis followed by a chronic, progressive demyelinating disease with clinical and histological similarities to the human demyelinating disease Multiple Sclerosis (MS). Studies were undertaken to evaluate the contribution of NOS2 generated NO in demyelination in MHV-infected mice. MHV-infected animals were treated daily with either 8 mg of aminoguanidine (AG), a selective inhibitor of NOS2 activity, or PBS by intraperitoneal (i.p.) injection. MHV-infection of mice resulted in 20% mortality in both groups with surviving mice clearing virus below levels of detection, as measured by plaque assay, by day 12 postinfection (p.i.). A significant decrease in the severity of clinical disease was observed in AG-treated animals as compared to mice receiving PBS at days 7 and 12 p.i. (P< or =0.001 and 0.003, respectively) however, by day 21 p.i. AG-treated mice exhibited the same severity of clinical disease as control animals. Examination of brain and spinal cords from infected mice revealed a pronounced reduction in the severity of inflammation at day 7 p.i. in mice treated with AG as compared to control mice. By day 12 p.i. there was a significant decrease (P< or =0.02) in the severity of demyelination in AG-treated mice as compared to control animals yet both PBS and AG treated mice had a similar degree of demyelination by day 21 p.i. Analysis of chemokine mRNA transcripts by RNase protection assay revealed that AG-treated mice had significantly lower levels (P < or = 0.007) of transcripts for the C-C chemokine monocyte chemoattractant protein-1 (MCP-1) at day 7 p.i. as compared to control animals. By day 12 p.i., AG-treated mice and control mice had similar levels of chemokine transcripts. Together, these data suggest that inhibition of NOS2/NO slows the progression of MHV-induced demyelination. One potential mechanism by which this may occur is through controlling inflammation through modulation of chemokine expression in the CNS.
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PMID:Inhibition of nitric oxide synthase-2 reduces the severity of mouse hepatitis virus-induced demyelination: implications for NOS2/NO regulation of chemokine expression and inflammation. 1019 Jun 90

To evaluate the effects of chronic liver diseases on mitochondrial DNA (mtDNA) transcription and replication, nuclear respiratory factor-1 (NRF-1) mRNA, mitochondrial transcription factor A (mtTFA) mRNA, a RNA component of ribonuclease (RNase) for mitochondrial RNA processing (MRP), mitochondrial cytochrome b mRNA, and mtDNA were measured in normal, chronically viral-hepatitic and cirrhotic human livers. The mRNA levels of the regulatory factors for mitochondrial gene (NRF-1 and mtTFA) and cytochrome b were significantly increased by chronic hepatitis (160, 280, and 175%, respectively) compared with those in normal livers, but were not different between cirrhotic and normal livers. On the other hand, concentrations of mtDNA and RNA component of RNase MRP were not different among normal, chronically hepatitic, and cirrhotic livers. These results suggest that either persistent hepatitis viral infection or repeated cell necrosis and regeneration in chronically hepatitic liver may be associated with increase in mtDNA transcription.
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PMID:Effects of chronic liver diseases on mitochondrial DNA transcription and replication in human liver. 1046 82

Replication of hepatitis delta virus (HDV) RNA occurs in the nuclei of infected cells. The replication is mediated by cellular factors containing an RNA polymerase II-like enzyme activity through a double rolling-circle mechanism and is regulated by delta antigens. In this study, UV cross-linking experiments were carried out to examine interactions between HDV RNA and proteins present in HeLa nuclear extract. Cellular proteins with molecular mass of 23 (p23), 36 (p36), 38 (p38), and 58 (p58) kDa bound to full-length HDV RNA of both genomic and antigenomic strands. Deletion analysis on the antigenomic strand mapped the interacting domain within a 79-nucleotide fragment but not at the ends of the rod-shaped viral RNA structure. The specificity of the RNA-protein interactions was demonstrated by competition experiments and the specific HDV RNA-binding proteins were purified through column chromatography. Electrophoresis mobility shift assay with the purified fractions demonstrated that the interaction between p36 and HDV RNA was relatively stable even in the presence of 0.5 M NaCl. Biochemical analysis including protein microsequencing identified the p36 as glyceraldehyde 3-phosphate dehydrogenase (GAPDH). RNase footprinting indicated that the UC-rich domain between nucleotides 379 and 414 of the HDV antigenomic RNA was involved in the GAPDH binding. Functional studies further demonstrated an enhancing effect of GAPDH on the ribozyme activity of HDV antigenomic RNA. In addition, in the presence of HDV RNA cellular GAPDH relocalized from the cytoplasm to the nucleus where HDV replication occurs. These results suggest that GAPDH is involved in the replication of HDV.
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PMID:Specific interaction between the hepatitis delta virus RNA and glyceraldehyde 3-phosphate dehydrogenase: an enhancement on ribozyme catalysis. 1081 69

Coronavirus contains three envelope proteins, M, E and S, and a nucleocapsid, which consists of genomic RNA and N protein, within the viral envelope. We studied the macromolecular interactions involved in coronavirus assembly in cells infected with a murine coronavirus, mouse hepatitis virus (MHV). Coimmunoprecipitation analyses demonstrated an interaction between N protein and M protein in infected cells. Pulse-labeling experiments showed that newly synthesized, unglycosylated M protein interacted with N protein in a pre-Golgi compartment, which is part of the MHV budding site. Coimmunoprecipitation analyses further revealed that M protein interacted with only genomic-length MHV mRNA, mRNA 1, while N protein interacted with all MHV mRNAs. These data indicated that M protein interacted with the nucleocapsid, consisting of N protein and mRNA 1, in infected cells. The M protein-nucleocapsid interaction occurred in the absence of S and E proteins. Intracellular M protein-N protein interaction was maintained after removal of viral RNAs by RNase treatment. However, the M protein-N protein interaction did not occur in cells coexpressing M protein and N protein alone. These data indicated that while the M protein-N protein interaction, which is independent of viral RNA, occurred in the M protein-nucleocapsid complex, some MHV function(s) was necessary for the initiation of M protein-nucleocapsid interaction. The M protein-nucleocapsid interaction, which occurred near or at the MHV budding site, most probably represented the process of specific packaging of the MHV genome into MHV particles.
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PMID:Characterization of the coronavirus M protein and nucleocapsid interaction in infected cells. 1093 23

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