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

Pulse-chase experiments after synchronous initiation of translation indicate that the larger Venzuelan equine encephalomyelitis (VEE) virus membrane glycoprotein E2, is derived by proteolytic cleavage of the precursor, PE2. The structural proteins of VEE virus strains representing each of the antigenic subtypes and varieties have been compared by discontinuous SDS-polyacrylamide gel electrophoresis. Nucleocapsid proteins of all isolates were similar in size (mol. wt. 35 to 36 X 10(3). The mol. wt. of E1 varied from 48 to 51 X 10(3) and the mol. wt. of E2 glycoproteins ranged from 53 to 59 X 10(3). Pixuna virus contained a third envelope glycoprotein of 59 X 10(3) mol. wt. in addition to the two major glycoproteins of mol. wt. 53 X 10(3) and 48 X 10(3) respectively. The isoelectric points (pI) of E1 and E2 for all VEE strains studied were approx. 7 and 9 respectively. Both glycoproteins of TC-83 virus induced precipitating antibodies which reacted only with the homologous purified E1 and E2 glycoproteins. Antibodies to E2 protein of each virus neutralized virus infectivity and inhibited the agglutination of goose erythrocytes by virions. Haemagglutination-inhibition tests using antisera to E2 glycoproteins of prototype viruses, representing each of the antigenic subtypes and varieties, differentiated the viruses into subtypes I, II, III and IV with subtype I divided into variants 1AB, 1C, 1D and 1E.
 ...
PMID:Biochemical and antigenic comparison of the envelope glycoproteins of Venezuelan equine encephalomyelitis virus strains. 11 35

Infections of rodents by murine coronaviruses can lead to chronic diseases of the central nervous system. These infections are interesting systems to study mechanisms which could be relevant for the pathogenesis of certain human diseases. One major factor influencing the outcome of infection is related to the virus. To understand the virological basis for neurovirulence we compared JHM-virus isolates with different biological properties. JHM-Wt causes only acute disease, JHM-Ts43 a demyelinating encephalomyelitis and a virus shedded from persistently infected cells (JHM-Pi) is not virulent at all. The spread of these viruses in glial cell cultures reflects their different neurovirulence for animals. The peplomer E2 of these viruses reveals structural and antigenic differences. We characterised the epitopes of E2 with a panel of monoclonal antibodies. Four epitopes are associated with regions important for neutralisation, cell fusion and attachment. More than five epitopes are not related to such functions. Epitopes differ in their location and accessibility on the E2 protein subunits between JHM-Wt, JHM-Ts43 and JHM-Pi. To identify epitopes in regions important for pathogenesis, we performed animal studies with variants selected by monoclonal antibodies. Variants changed in a defined epitope (E2-Ba) induce in Balb/c mice a chronic disease. Variants changed in only one of the other three neutralisation epitopes induce acute disease. These results support and extend the observation that the peplomer protein E2 is a major determinant for virulence and antigenic variability of coronaviruses 1,4,5,6,8,10,17,19,22,23. Increasing evidence had been obtained that certain structural features of this protein are important for the cell tropism of the virus. Furthermore, this protein influences strongly the type and specificity of immune responses against viral and host antigens. The highly advanced knowledge on structure and replication of coronaviruses will be of great value to analyze further mechanisms leading to inflammatory demyelinating diseases associated with a persistent virus infection.
 ...
PMID:Coronavirus JHM induced demyelinating disease: specific domains on the E2-protein are associated with neurovirulence. 244 42

Intracerebral inoculation of murine coronavirus JHM into 2- to 3-day-old Wistar Furth rats causes an acute encephalomyelitis, while inoculations at 10 days of age usually result in hind leg paralysis. To examine the distribution of viral antigens within this infected central nervous system (CNS) tissue, we used the avidin-biotin-peroxidase method to detect monoclonal and polyclonal antibodies bound to JHM structural proteins; in addition we used the Western blot technique to detect viral proteins. Our study demonstrated the following characteristics: Infected neuronal and glial cells produced viral nucleocapsid and E2 glycoprotein. The synthesis of these viral structural proteins was not restricted to cells in any particular part of the central nervous system. While JHM E2 proteins could be detected in individual cells of JHM-infected CNS tissue, the relative level of detectable E2 protein in the total CNS tissue of infected rats was reduced by more than 13-fold compared with JHM-infected tissue culture cells. Hippocampus neuronal cells provided a sensitive indication of JHM infection. These cells invariably contained antigens in both acutely and chronically infected animals. The distribution of cells containing viral antigens differed markedly for JHM-induced acute encephalitis and chronic demyelinating disease. Acutely infected brains had large lesions containing low levels of viral antigen scattered throughout the brain. One percent to ten percent of histologically normal cells in many parts of the brain contained viral antigens; in addition, more neuronal cells than glial cells were observed to be antigen-positive. The hippocampus appeared normal with hematoxylin-eosin staining; however, a scattered infection of neuronal cells was apparent.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Analysis of JHM central nervous system infections in rats. 301 91

The hemagglutination (HA) domains of the Venezuelan equine encephalomyelitis (VEE) and the eastern equine encephalomyelitis (EEE) viruses providing the interaction of virions and red blood cells were studied with the use of a panel of 17 hemagglutination inhibition (HI) monoclonal antibodies (MAbs). A highly conserved domain (C domain) forming alphavirus-group-reactive MAbs was identified in the E2 protein of the VEE and EEE viruses. These MAbs inhibited HA of the western equine encephalomyelitis, Semliki Forest, Sindbis, Getah, Aura, Chikungunya and Pixuna viruses. The involvement of amino acid residues 59 and 232 in the formation of the C region was demonstrated by sequencing the gene encoding the E2 protein of three escape variants of the VEE virus.
 ...
PMID:Analysis of the hemagglutination activity domains of the Venezuelan equine encephalomyelitis and eastern equine encephalomyelitis viruses. 858 35

Enzyme immunoassay (EIA) with sixty types of monoclonal antibodies (MAbs) was used to study cross-reactive epitopes on the attenuated and virulent strains of the Eastern equine encephalomyelitis (EEE) and Venezuelan equine encephalomyelitis (VEE) viruses. All three structural proteins of the EEE and VEE viruses were demonstrated to have both cross-reactive and specific antigenic determinants. The glycoprotein E1 of EEE and VEE viruses possesses three cross-reactive epitopes for binding to MAbs. The glycoprotein E2 has a cluster of epitopes for 20 cross-reacting MAbs produced to EEE and VEE viruses. Cross-reactive epitopes were localised within five different sites of glycoprotein E2 of VEE virus and within four sites of that of the EEE virus. There are no cross-neutralising MAbs to the VEE and EEE viruses. Only one type of the protective Mabs was able to cross-protect mice against lethal infection by the virulent strains of the VEE and EEE viruses. Eight MAbs blocked the hemagglutination activity (HA) of both viruses. Antigenic alterations of neutralising and protective sites were revealed for all attenuated strains of the VEE and EEE viruses. Comparative studies of the E2 proteins amino acid sequences show that the antigenic modifications observed with the attenuated strains of the VEE virus may be caused by multiple amino acid changes in positions 7, 62, 120, 192 and 209-213. The escape-variants of the VEE virus obtained with cross-reactive MAbs 7D1, 2D4 and 7A6 have mutations of the E2 protein at positions 59, 212-213 and 232, respectively. Amino acid sequences in these regions of the VEE and EEE viruses are not homologous. These observations indicate that cross-reactive MAbs are capable of recognising discontinuous epitopes on the E2 glycoprotein.
 ...
PMID:Glycoproteins E2 of the Venezuelan and eastern equine encephalomyelitis viruses contain multiple cross-reactive epitopes. 897 33