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)

Theiler's murine encephalomyelitis virus (TMEV)-induced demyelinating disease in mice is a well established animal model for human multiple sclerosis (MS). Identification of pathogenic epitopes may be helpful in understanding the pathogenesis of this immune-mediated disease. In order to analyze the viral epitopes, we have generated approx. 150 recombinant lambda gt11 clones expressing various capsid areas of TMEV. Six predominant areas, ranging from 13-26 amino acid residues, (3 in VP1, 2 in VP2 and 1 in VP3) are readily recognized by conformation-independent antibodies from virus-infected mice. These areas have been designated as A-1A (VP1 13-27th residues), A-1B (VP1 145-167), A-1C (VP1 251-276), A-2A (VP2 2-14), A-2B (VP2 165-179), and A-3A (tentatively VP3 24-43). Antibodies from TMEV-infected susceptible SJL/J mice strongly react with A-1B, A-2A and A-2B, in contrast to antibodies from resistant BALB/c mice which mainly recognize A-1A and A-2A. Interestingly, the reactivity pattern of antibodies from TMEV-infected mice are somewhat different from that of antibodies from TMEV-immunized mice. Although the majority of antibodies in TMEV-infected mice recognizes conformation-dependent epitopes, the differential recognition of the conformation-independent antibody epitopes by susceptible mice may play a role in TMEV-induced demyelination.
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PMID:Identification and localization of a limited number of predominant conformation-independent antibody epitopes of Theiler's murine encephalomyelitus virus. 137 Dec 68

Intracerebral injection of mice with Theiler's murine encephalomyelitis virus results in chronic demyelination in susceptible strains, and serves as a model system for the study of multiple sclerosis. The role of individual epitopes in the disease process remains to be elucidated. Random fragments of DNA from the viral capsid protein genome covering the coding regions from VP1, VP2, and VP3 have been expressed in the lambda gt11 vector system. Fusion proteins from the clones were expressed and probed with antibodies from both resistant and susceptible strains of mice. Each strain displays a distinctive pattern with certain fusion proteins recognized by all of the strains and others recognized uniquely by either the susceptible or the resistant strains.
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PMID:Detection of restricted predominant epitopes of Theiler's murine encephalomyelitis virus capsid proteins expressed in the lambda gt11 system: differential patterns of antibody reactivity among different mouse strains. 169 32

Theiler's murine encephalomyelitis virus (TMEV)-induced demyelinating disease serves as a relevant animal model of human multiple sclerosis. Myelin damage induced by TMEV infection appears to be immune mediated. Disease susceptibility correlates best with the temporal development of chronic, high levels of TMEV-specific, MHC class II-restricted delayed-type hypersensitivity (DTH) responses. We have proposed a model wherein these responses result in CNS demyelination via a macrophage-mediated terminal nonspecific bystander response. As virus-specific DTH responses appear to be intimately involved in the pathogenicity of CNS demyelination, it is critical to determine the specificity of these responses so that effector T cells specific for potential pathogenic epitopes can be targeted to serve as the focus of specific immunoregulatory processes. In the current study, the capsid protein specificity of the TMEV-susceptible SJL/J and TMEV-resistant C57BL/6 mouse strains was examined. DTH and Tprlf responses in both infected and immunized SJL/J mice were found to be predominantly directed toward the VP2 capsid protein, specifically to an epitope(s) contained within the N-terminal 150 amino acids of VP2. This same epitope was also found to be dominant in priming SJL/J mice for responses to challenge with intact virions. In contrast, the T cell-mediated responses of TMEV-resistant C57BL/6 mice did not show preferential reactivity towards VP2, because all three major capsid proteins (VP1, VP2, and VP3) elicited responses with essentially equal potency. The relationship of the restricted VP2 T cell epitope to predicted neutralizing antibody sites on the VP2 protein is discussed as is the potential use of this epitope for prevention and/or treatment of TMEV-induced demyelinating disease via the induction of epitope-specific tolerance.
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PMID:Class II-restricted T cell responses in Theiler's murine encephalomyelitis virus-induced demyelinating disease. IV. Identification of an immunodominant T cell determinant on the N-terminal end of the VP2 capsid protein in susceptible SJL/J mice. 170

The structure of Mengo encephalomyelitis virus was refined at 3 A resolution with a final R-factor of 0.221 and a root-mean-square deviation from idealized bond lengths of 0.019 A for 10 A to 3 A data with F greater than or equal to 3 sigma(F). The Hendrickson-Konnert refinement was restrained by the phases derived from the molecular replacement averaging procedure and constrained by the icosahedral symmetry of the virus. The virus consists of 60 protomers each having three major subunits, VP1, VP2 and VP3, along with one smaller internal protein, VP4. The three major subunits form similar eight-stranded beta-barrel structures. Alterations in the original sequence were found at position 45 in VP1 (Arg to Ala) and at position 58 in VP3 (Met to Val). The residues in loops I and II of VP1 (82 to 102), the "FMDV loop" in VP1 (205 to 213), the flexible loop of VP3 in the putative receptor attachment site (175 to 185) as well as the terminal regions 260 to 268 in VP1, 253 to 256 in VP2 and 13 to 15 in VP4 were built or modified in regions of weak density. The variation in temperature factors at the end of the refinement is over a wide range (from 2 to 80 A2), with the disordered outer and inner regions showing high mobility. Four cis proline residues, 105 in VP1, 85 and 152 in VP2 and 59 in VP3, have been identified. The disulfide bridge Cys86 to Cys88 in VP3 has been characterized. One phosphate ion and 233 water positions were included in the refinement. It is suggested that this phosphate is associated with the receptor attachment site. There are two major hydrogen-bonding networks involving solvent atoms; one involving only the subunits of a protomer, and the other connecting the protomers in a pentamer. The distribution of atom types around the icosahedral symmetry axes shows that the 5-fold channel is more hydrophobic than that along the 3-fold axis and that there are more charged residues around the 2-fold axis. The analysis of contacts between the different subunits supports the assignment of the protomeric unit. The five protomers that form the pentameric unit are held together by interactions involving the smaller VP4 protein and the amino termini of VP1 and VP3. The pentamers are associated by means of the amino-terminal region of the VP2 subunits, the beta F strand of the VP3 subunits, the C terminus of the VP4 subunits and the electrostatic helical (alpha A) interactions of VP2 subunits across the icosahedral 2-fold axes. The superposition of the corresponding subunits of Mengo virus, human rhinovirus 14 and southern bean mosaic virus has provided an improved sequence alignment. The largest structural similarity is between the VP3 subunits of Mengo virus and rhinovirus, while the least similarity is between the VP1 subunits. The various specialized insertions in the different subunits can be associated with specific functional requirements.
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PMID:Structural refinement and analysis of Mengo virus. 215 78

Theiler murine encephalomyelitis viruses (TMEVs) are picornaviruses that cause enteric and neurological disease in mice. The GDVII strain and other members of the GDVII subgroup are highly virulent and cause an acute, fatal polioencephalomyelitis following intracerebral inoculation, whereas the DA stain and other members of the TO subgroup cause a persistent, demyelinating infection. We previously produced a full-length, infectious DA cDNA clone. We now describe the generation of a full-length, infectious GDVII cDNA clone and the subsequent production of intratypic chimeric cDNAs and intratypic recombinant viruses. Inoculation of the recombinant viruses into mice demonstrated that a major determinant of TMEV neurovirulence is within the GDVII 1B (capsid protein VP2)-2C coding region, most likely in the GDVII 1B (VP2)-2A coding region. Genomic sequences 5' to this region of GDVII RNA also contribute to expression of the full neurovirulence phenotype. These data demonstrate the multigenic nature of TMEV neurovirulence, as has been reported for other viruses.
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PMID:Neurovirulence determinants of genetically engineered Theiler viruses. 216 33

The hemagglutinating-inhibition (HI) test was used to detect antibodies for Theiler's murine encephalomyelitis virus (TMEV), and the virus was isolated from sero-positive mice derived from colonies in Japan. HI antibody was detected in conventional mice (38.7%; 137/354) at titers ranging from 1:8 to 1:512, but it not in SPF mice (0/90). To isolate the virus, weanling mice inoculated intracerebrally with samples obtained from sero-positive mice were sacrificed and 10% brain homogenates were subcultured. New isolates designated as YOC and AB strains were obtained, and their physicochemical and biological properties were characterized. The results indicated that the new isolates were similar to Theiler's original (TO) strain according to the following observations of persistent paralysis of the hind limbs, resistance to ether treatment, a particles size of 10 approximately 50 nm in diameter, stability at pH 3, a density of 1.35 g/cm3 and three major and one minor viral proteins, (VPO; 38 Kd, VP 1; 33 Kd, VP2; 32Kd, VP3; 25 Kd). Immunoblotting analysis also showed that VP 2 of YOC and encephalomyocarditis virus of the Cardiovirus group, reacted strongly with the antisera against the viruses as well as with the GDVII strain. These results suggest that TMEV infection does exist in conventional mouse colonies in Japan, and that these viruses resemble the TO strain of TMEV.
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PMID:Theiler's murine encephalomyelitis virus--characterization of newly isolated viruses from Japanese mouse colonies. 224 66

To explore structural features of the Theiler murine encephalomyelitis virion, we have constructed a three-dimensional model of the capsid proteins (VP1, VP2, and VP3) of the BeAn strain based on the atomic coordinates of the closely related Mengo virus. By superimposition of amino acid differences between BeAn virus and another Theiler virus strain, GDVII, on the three-dimensional model, clusters of differences were found in four distinct sites; the VP1 third corner, the VP2 "puff," and the VP3 first corner and "knob." These clusters, which are found on the surface of the virion, may represent neutralizing immunogenic sites that have come under selective pressure from neutralizing antibodies. Furthermore, the putative viral receptor binding site ("pit") of the two Theiler virus strains was found to be markedly conserved.
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PMID:Three-dimensional model of the capsid proteins of two biologically different Theiler virus strains: clustering of amino acid difference identifies possible locations of immunogenic sites on the virion. 245 72

No cross-reaction could be detected between purified myelin basic proteins (MBP) from mouse, rat or human origins and envelope proteins of viruses suspected of inducing demyelinating processes. In the experimental model using Theiler's murine encephalomyelitis virus, competition radioimmunoassay failed to detect any cross-reaction between MBP and VP1, VP2 and VP3 envelope antigens. In the human situation, antibodies against SV5 and measles viruses, both etiologically linked with multiple sclerosis, also failed to recognize MBP. These results rule out molecular mimicry as a cause of demyelination.
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PMID:Lack of cross-reaction between myelin basic proteins and putative demyelinating virus envelope proteins. 247 71

The spleen T cell proliferative response of SJL/J mice primed by intracerebral inoculation of Theiler's murine encephalomyelitis virus (TMEV) was characterized in vitro. A dose-response [3H]thymidine incorporation was found with TMEV, but not with unrelated viruses. The maximum response was obtained at doses of 5 X 10(5) cells per well with cultures of 96 h duration. Viral capsid proteins VP1 and VP2 carried the antigenic determinants for the T cell response, VP3 playing no role in the in vitro cellular immune response. The antibody synthesis showed the same antigenic specificity as the cellular one, as only antibodies against VP1 and VP2 could be found in the sera of the immunized animals.
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PMID:Characterization of the immune response to intracerebral inoculation of Theiler's murine encephalomyelitis virus: fine protein specificity of the splenic T cell and humoral antibody response. 254 54

Humoral antibody responses to Theiler's murine encephalomyelitis virus (TMEV) capsid proteins were examined. Rabbit antisera produced against the native BeAn strain of TMEV and against the isolated capsid proteins (VP1, VP2 and VP3) were tested for their ability to bind or neutralize virus and to inhibit the virus-induced haemagglutination of human O+ erythrocytes. Western immunoblotting analysis showed that isolated VP1, VP2 and VP3 each primed for a specific antibody response, but that native virions primed for antibodies specific for VP1 and VP2, but not VP3. Virus neutralization studies revealed that a dominant TMEV neutralizing determinant(s) lay on VP1, as did the haemagglutinating determinant. The possible location of the neutralizing epitopes are discussed on the basis of molecular modelling of the predicted amino acid sequence of TMEV from that of the closely related Mengo virus for which the three-dimensional structure is known.
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PMID:Characterization and specificity of humoral immune responses to Theiler's murine encephalomyelitis virus capsid proteins. 282 57


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