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)

MHV-A59 produces acute encephalitis, acute hepatitis and chronic demyelination in infected mice. MHV-2 produces only hepatitis and mild meningitis but without encephalitis or demyelination. We have previously studied a set of recombinant viruses between these two strains. The common denominator of viruses that produced encephalitis was a membrane (M) gene derived from MHV-A59. Thus to study the potential contribution of the M gene to acute encephalitis, chimeric viruses were produced in which the M gene of MHV-A59 was substituted with the M gene of MHV-2 by targeted recombination. A control virus was produced in which the M gene of A59 was recombined back into an A59 background. Viruses were then analyzed for their biologic properties and compared with the phenotypes of MHV-A59 and MHV-2 by histopathology and plaque assays for viral titers in organs following intracerebral (IC) inoculation. All three chimeric viruses had a phenotype similar to MHV-A59. Thus, the replacement of the M gene of MHV-A59 with that of MHV-2 is insufficient to produce a phenotype that lacks encephalitis similar to MHV-2.
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PMID:Targeted recombination between MHV-2 and MHV-A59 to study neurotropic determinants of MHV. 978 27

Between 1986 and 1996, 263 patients, 156 females and 107 males, affected by oral lichen planus (OLP), were followed at the Division of Oral Medicine and Pathology, University of Naples 'Federico II', Italy, and at the Institute of Dentistry and Maxillofacial Surgery, University of Bari, Italy. During this follow-up, the possible association of OLP with oral squamous cell carcinoma (SCC), together with the possible association of OLP, oral SCC and chronic HCV-hepatitis, were investigated. 14 cases (5.32%) were known to have developed oral SCC: 10 (3.8%) in an area of pre-existing OLP, 3 (1.14%) in other sites, in 1 case the diagnosis of OLP and SCC was synchronous (0.38%). 3 patients were positive for anti-HCV antibody. Many carcinomas were in areas of reticular/plaque OLP. 3 patients had multiple simultaneous sites of oral involvement (21.42%); 5 patients developed oral SCC in different sites during the follow-up period (35.71%). These data, together with a clear histological evidence of progression to carcinoma within OLP lesions, suggest the probability of some cases of at least OLP having an intrinsic property predisposing to neoplastic transformation, confirming previous studies. For these reasons, the authors think that it is necessary to follow-up the patients regularly at least annually and possibly for life for the early diagnosis of a possible neoplastic degeneration. These consideration are particularly important in the case of atrophic or erosive OLP, and plaque OLP, especially when involving the dorsum of tongue.
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PMID:The possible association between oral lichen planus and oral squamous cell carcinoma: a clinical evaluation on 14 cases and a review of the literature. 981 16

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

The mouse hepatitis virus (MHV) spike glycoprotein, S, has been implicated as a major determinant of viral pathogenesis. In the absence of a full-length molecular clone, however, it has been difficult to address the role of individual viral genes in pathogenesis. By using targeted RNA recombination to introduce the S gene of MHV4, a highly neurovirulent strain, into the genome of MHV-A59, a mildly neurovirulent strain, we have been able to directly address the role of the S gene in neurovirulence. In cell culture, the recombinants containing the MHV4 S gene, S4R22 and S4R21, exhibited a small-plaque phenotype and replicated to low levels, similar to wild-type MHV4. Intracranial inoculation of C57BL/6 mice with S4R22 and S4R21 revealed a marked alteration in pathogenesis. Relative to wild-type control recombinant viruses (wtR13 and wtR9), containing the MHV-A59 S gene, the MHV4 S gene recombinants exhibited a dramatic increase in virulence and an increase in both viral antigen staining and inflammation in the central nervous system. There was not, however, an increase in the level of viral replication in the brain. These studies demonstrate that the MHV4 S gene alone is sufficient to confer a highly neurovirulent phenotype to a recombinant virus deriving the remainder of its genome from a mildly neurovirulent virus, MHV-A59. This definitively confirms previous findings, suggesting that the spike is a major determinant of pathogenesis.
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PMID:Pathogenesis of chimeric MHV4/MHV-A59 recombinant viruses: the murine coronavirus spike protein is a major determinant of neurovirulence. 1043 65

A complete DNA copy of the genome of a Jeryl Lynn strain of mumps virus (15,384 nucleotides) was assembled from cDNA fragments such that an exact antigenome RNA could be generated following transcription by T7 RNA polymerase and cleavage by hepatitis delta virus ribozyme. The plasmid containing the genome sequence, together with support plasmids which express mumps virus NP, P, and L proteins under control of the T7 RNA polymerase promoter, were transfected into A549 cells previously infected with recombinant vaccinia virus (MVA-T7) that expressed T7 RNA polymerase. Rescue of infectious virus from the genome cDNA was demonstrated by amplification of mumps virus from transfected-cell cultures and by subsequent consensus sequencing of reverse transcription-PCR products generated from infected-cell RNA to verify the presence of specific nucleotide tags introduced into the genome cDNA clone. The only coding change (position 8502, A to G) in the cDNA clone relative to the consensus sequence of the Jeryl Lynn plaque isolate from which it was derived, resulting in a lysine-to-arginine substitution at amino acid 22 of the L protein, did not prevent rescue of mumps virus, even though an amino acid alignment for the L proteins of paramyxoviruses indicates that lysine is highly conserved at that position. This system may provide the basis of a safe and effective virus vector for the in vivo expression of immunologically and biologically active proteins, peptides, and RNAs.
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PMID:Rescue of mumps virus from cDNA. 1077 22

A-2 plaque virus (A2 virus) was originally isolated from the icteric-phase sera of US servicemen with viral hepatitis in the 1960s, but apart from a preliminary characterization little is known about the agent. We have now successfully cloned and sequenced the complete viral genome. A2 viral RNA consists of 7312 nucleotides, excluding the 62 nucleotide poly(A) tract at the 3' end, with one large open reading frame. Although clearly a member of the Picornaviridae, there is low homology to the available sequences, suggesting it is only loosely related to the classic rhino/enterovirus genus. In addition, there was no reactivity with group specific monoclonal antibody blends against polioviruses, enteroviruses 70 and 71, coxsackievirus B, and echoviruses. Two tamarins were inoculated with A2 virus to study viral pathogenesis. Both animals that received A2 virus became transiently viremic 1 week after the infection, as determined by RT-PCR, and they developed an antibody response to A2 virus. However, no physical signs or biochemical abnormalities, including elevated liver transaminases, were observed. In addition, no liver samples from patients with fulminant hepatitis (n = 7) or controls (n = 7) were positive for A2 viral RNA nor was anti-A2 neutralizing antibody detected in sera from hepatitis patients (n = 14), healthy laboratory donors (n = 14), or US blood donors (n = 33); however, most sera contained antibodies reactive with A2 virus proteins. These results suggest that A2 virus is a new member of the Picornaviridae but that its pathogenicity in nonhuman primates and association with human disease still need to be determined.
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PMID:Sequencing and characterization of A-2 plaque virus: A new member of the Picornaviridae family. 1087 59

A recombinant mesogenic NDV strain, Beaudette C, and an engineered recombinant NDV expressing an additional gene were generated entirely from cloned cDNAs. For this purpose, a full-length cDNA clone of the virus genome, represented in eight different subgenomic fragments, was assembled in a transcription plasmid between a T7 RNA polymerase promoter and a hepatitis delta virus ribozyme sequence. Infectious NDV could be generated in the cells infected with recombinant vaccinia virus, which expressed T7 RNA polymerase, by simultaneous expression of antigenome-sense NDV RNA from the full-length plasmid and NDV NP, P, and L proteins from cotransfected plasmids. Recombinant virus was then amplified and recovered, either after inoculation of transfection supernatant into the allantoic cavity of embryonated specific-pathogen-free eggs or after further passage in cell culture. Characterization of the recombinant NDV showed similarities in growth and pathogenicity to that of the parental wild-type virus. By using this system, a recombinant NDV containing a foreign gene encoding chloramphenicol acetyltransferase (CAT) was generated. To do this, the CAT transcription cassette containing the CAT open reading frame, flanked by NDV gene start and gene end sequence motifs, was inserted into the region between the HN and L genes of the full-length cDNA. This construct was then used in the generation of a recombinant NDV expressing CAT protein. The CAT gene was maintained stably for at least eight passages without any detectable loss of the gene from the recombinant. Generation of the recombinant virus, however, was associated with reduced plaque size, slower replication kinetics, and more than 100-fold decrease in yield. In addition, the virus showed an increase in mean death time for eggs and a lower intracerebral pathogenicity index in day-old chicks, implicating attenuation of the recombinant virus. Thus, introduction of an additional gene into the NDV genome represents a method to achieve growth retardation and attenuation. These results also indicate that NDV can be engineered to express foreign protein stably and can be manipulated in the future for use as a vaccine vector.
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PMID:Recovery of a virulent strain of newcastle disease virus from cloned cDNA: expression of a foreign gene results in growth retardation and attenuation. 1111 92

A novel method was developed to assemble a full-length infectious cDNA of the group II coronavirus mouse hepatitis virus strain A59 (MHV-A59). Seven contiguous cDNA clones that spanned the 31.5-kb MHV genome were isolated. The ends of the cDNAs were engineered with unique junctions and assembled with only the adjacent cDNA subclones, resulting in an intact MHV-A59 cDNA construct of approximately 31.5 kb in length. The interconnecting restriction site junctions that are located at the ends of each cDNA are systematically removed during the assembly of the complete full-length cDNA product, allowing reassembly without the introduction of nucleotide changes. RNA transcripts derived from the full-length MHV-A59 construct were infectious, although transfection frequencies were enhanced 10- to 15-fold in the presence of transcripts encoding the nucleocapsid protein N. Plaque-purified virus derived from the infectious construct replicated efficiently and displayed similar growth kinetics, plaque morphology, and cytopathology in murine cells as did wild-type MHV-A59. Molecularly cloned viruses recognized the MHV receptor (MHVR) for docking and entry, and pretreatment of cells with monoclonal antibodies against MHVR blocked virus entry and replication. Cells infected with molecularly cloned MHV-A59 virus expressed replicase (gene 1) proteins identical to those of laboratory MHV-A59. Importantly, the molecularly cloned viruses contained three marker mutations that had been derived from the engineered component clones. Full-length infectious constructs of MHV-A59 will permit genetic modifications of the entire coronavirus genome, particularly in the replicase gene. The method has the potential to be used to construct viral, microbial, or eukaryotic genomes approaching several million base pairs in length and used to insert restriction sites at any given nucleotide in a microbial genome.
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PMID:Systematic assembly of a full-length infectious cDNA of mouse hepatitis virus strain A59. 1236 49

The targeted RNA recombination was attempted to substitute the membrane (M) protein gene and part of the nucleocapsid (N) protein gene of mouse hepatitis virus with the corresponding sequences from bovine coronavirus. Using a defective interfering (DI) RNA-like cDNA construct derived from pMH54, 690 nucleotides representing the entire M gene and the 5' most 915 nucleotides of the N gene of the mouse hepatitis virus Albany 4 mutant were attempted to be replaced. Upon infection of cells with Albany 4 followed by transfection with synthetic RNA transcribed from the DI-like cDNA construct, recombinant mouse hepatitis viruses as the large plaque forming phenotype were isolated by plaque assays at the non-permissive temperature of 391 degrees C. By RT-PCR and sequencing, those large plaque phenotypes were confirmed to have contained the thermostable phenotype marker derived from the transfected RNA, demonstrating that recombination occurred between the Albany 4 genomic RNA and the in vitro RNA transcripts. Further analysis of the recombinant viruses indicated that there combination had taken place within the region of 222 nucleotides between positions 916 and 1,137 of the N gene. This is the region immediately downstream of the replacement sequence and the start of the temperature resistant phenotype marker. The results suggest that the M and part of the N genes of bovine coronavirus may not be able to complement the function of those of mouse hepatitis virus. This study redirects our current approach of utilizing the MHV targeted RNA recombination as a means to study bovine coronavirus genetics towards the construction of an infectious cDNA clone.
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PMID:Targeted RNA recombination of the membrane and nucleocapsid protein genes between mouse hepatitis virus and bovine coronavirus. 1244 93

The pathogenicity of serotype 8 group I avian adenovirus (GIAAV) strains (TR630 and Saga97 strains) from inclusion body hepatitis (IBH) against cyclophosphamide (CY)-treated 3-wk-old specific-pathogen-free (SPF) chickens was examined. SPF chickens were inoculated intramuscularly with 10(7) plaque-forming units of viruses. Both strains from IBH could produce hydropericardium and mortality in CY-treated chickens as hydropericardium syndrome (HPS) that serotype 4 GIAAV strains cause, although they could not induce either hydropericardium or mortality in nontreated chickens. Histologically, hepatocytic necrosis with intranuclear inclusions, pancreatic acinar necrosis with intranuclear inclusions, and epicardial edema were seen in CY-treated chickens inoculated with GIAAV from IBH. Immunohistochemically, these inclusions were positive against GIAAV antigen. There were neither histologic lesions nor positive reactions against GIAAV antigen in nontreated chickens inoculated with GIAAV from IBH. From the present findings, pathogenic characteristics of IBH strains and HPS strains in the chickens were essentially the same.
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PMID:Reproduction of hydropericardium syndrome in three-week-old cyclophosphamide-treated specific-pathogen-free chickens by adenoviruses from inclusion body hepatitis. 1271 73


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