Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0014070 (encephalomyelitis)
 13,017 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Vaccinia-virus (VV) recombinants encoding either the nucleocapsid (N) or the spike (S) protein of MHV-JHM were constructed to study the role of the immune response against defined coronavirus antigens. For the S-protein, a fusogenic (Sfus+) or non fusogenic variant (Sfus-) of the gene was inserted into the VV genome. A strong protection against acute encephalomyelitis (AE) was mediated in Lewis rats which were immunized by VV-Sfus+ and challenged with an otherwise lethal dose of MHV-JHM before the induction of S-specific IgG antibodies. By contrast, a VV recombinant encoding a variant non fusogenic S-protein or the N-protein was not capable conferring protection. In addition, we demonstrated that MHV-JHM S-specific IgG antibodies elicited before MHV-JHM challenge modulated the disease process, changing it from an acute disease to subacute demyelinating encephalomyelitis (SDE).
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PMID:Recombinant vaccinia viruses which express MHV-JHM proteins: protective immune response and the influence of vaccination on coronavirus-induced encephalomyelitis. 820 61

The neurotropic mouse hepatitis virus MHV-JHM induces central nervous system (CNS) demyelination in Lewis rats that pathologically resembles CNS lesions in multiple sclerosis. The mechanisms of MHV-JHM-induced demyelination remain unclear and several studies have implicated the role of the immune response in this process. We have shown previously that protective immunity against MHV-JHM-induced encephalomyelitis was induced by immunization with a vaccinia virus (VV) recombinant expressing MHV-JHM S-protein (VV-S). Here, we present evidence that the time of MHV-JHM challenge after immunization with VV-S plays a critical role in protective immunity. The induction of virus-neutralizing S-protein-specific antibodies prior to the MHV-JHM challenge modulates the disease process and a subacute encephalomyelitis based on a persistent virus infection developed. Typical pathological alterations were lesions of inflammatory demyelination. In addition, the results indicate that after seroconversion, CD8+ T cells were no longer essential for virus elimination in contrast to their role in protection during acute encephalomyelitis.
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PMID:Coronavirus-induced encephalomyelitis: balance between protection and immune pathology depends on the immunization schedule with spike protein S. 904 33

Coronaviruses display a large phenotypic variability, which may be an important factor for diversification and selection. Previous studies have demonstrated that the S-protein is an essential determinant of virulence and pathogenicity. Therefore we studied the S-gene as an indicator molecule for selection processes employing two different MHV-JHM variants. First, Lewis-rats were infected with MHV-JHM-Pi, a variant that causes demyelinating disease after several weeks p.i. It was not possible to isolate infectious MHV-JHM-Pi from such rats, although viral proteins were expressed. The S-gene was rescued directly from brain tissue employing RT-PCR technology. The amplicons were sequenced in bulk or at the level of single clones. We detected no evidence for an increase of S-gene mutants during the length of time. Only few mutations were found at the clonal level. The changes were distributed throughout the analysed S-gene fragments without a predilection in their location. The frequency of mutation remained low within a range of 0.03 to 0.5 mutations per thousand nucleotides. As a second approach, we sequenced the S-genes of viruses isolated from brain tissue infected with MHV-JHM-ts43. Infection of adult Lewis rats with that mutant resulted several weeks to months p.i. in demyelinating encephalomyelitis. The S-gene of this virus contains an insertion of 423 bp in the S1 region, which is identical to a polymorphic region described for MHV-4. In contrast to JHM-Pi, infectious MHV-JHM-ts43 was readily to isolate from brain tissue. The S-gene sequences of virus isolated 45-106 days p.i. from diseased rats were identical with that of the input virus. These results show, that during a persistent infection of Lewis-rats the S-gene was highly conserved.
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PMID:Coronavirus infection and demyelination. Sequence conservation of the S-gene during persistent infection of Lewis-rats. 978 56

Plasminogen activators (PAs) and matrix metalloproteinases (MMPs) are considered to play an important role in the pathogenesis of multiple sclerosis. Experimental autoimmune encephalomyelitis (EAE) is widely used as an animal model of multiple sclerosis. Whereas several studies have addressed the expression of various MMPs and their inhibitors in the pathogenesis of EAE, the expression of the molecules of the PA system during EAE has not been reported previously. The present study was undertaken to investigate the expression of the molecules of the PA system (tPA, uPA, PAI-1, uPAR, LRP), as well as several members of the MMP family and their inhibitors in the course of actively induced EAE in BALB/c mice. During clinical EAE, the PA system was up-regulated in the central nervous system at several levels. Induction of expression of tPA and PAI-1 transcripts was detected in activated astrocytes in the white matter. Inflammatory cells expressed uPA receptor, uPAR. In situ zymography demonstrated the presence of increased tPA and uPA activities in the areas of the inflammatory damage. Accumulation of fibrin, fibronectin, and vitronectin immunoreactivity was seen in perivascular matrices of symptomatic animals. In addition, transcription of MT1-MMP and metalloelastase (in inflammatory cells), and TIMP-1 (in activated astrocytes) was induced during EAE. Increased gelatinolytic activity was detected at the sites of inflammatory cell accumulation by in situ zymography of fluorescently labeled gelatin; substrate gel zymography identified the up-regulated gelatinolytic activity as gelatinase B. Overall, our study demonstrates concurrent induction of PA and MMP systems during active EAE, supporting further the concept that the neuroinflammatory damage in EAE involves altered balance between multiple extracellular proteases and their inhibitors.
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PMID:Coordinated induction of extracellular proteolysis systems during experimental autoimmune encephalomyelitis in mice. 1173 72

Early in the pathogenesis of multiple sclerosis, the blood-brain barrier is compromised, which leads to deposition of the plasma proteins fibronectin and vitronectin in cerebral parenchyma. In light of our previous finding that microglial activation in vitro is strongly promoted by fibronectin and vitronectin, we set out to examine the possibility that modulation of microglial activation by fibronectin or vitronectin is an important regulatory mechanism in vivo. In an experimental autoimmune encephalomyelitis mouse model of demyelination, total brain levels of fibronectin and vitronectin were strongly increased and there was a close relationship between fibronectin and vitronectin deposition, microglial activation, and microglial expression of matrix metalloproteinase-9. In murine cell culture, flow cytometry for MHC class I and gelatin zymography revealed that microglial activation and expression of pro-matrix metalloproteinase-9 were significantly increased by fibronectin and vitronectin. Function-blocking studies showed that the influence of fibronectin and vitronectin was mediated by the alpha(5)beta(1) and alpha(v)beta(5) integrins, respectively. Taken together, this work suggests that fibronectin and vitronectin deposition during demyelinating disease is an important influence on microglial activation state. Furthermore, it provides the first evidence that the alpha(5)beta(1) and alpha(v)beta(5) integrins are important mediators of microglial activation.
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PMID:Fibronectin- and vitronectin-induced microglial activation and matrix metalloproteinase-9 expression is mediated by integrins alpha5beta1 and alphavbeta5. 1754 54