Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Infection of HeLa cells by poliovirus results in an abrupt inhibition of host cell protein synthesis. It is thought that the mechanism of this inhibition involves proteolytic cleavage of the p220 component of the cap-binding protein complex, thereby causing functional inactivation of the cap-binding protein complex and preventing capped (cellular) mRNAs from binding ribosomes. Current data suggest that the viral proteinase 2A indirectly induces p220 cleavage via alteration or activation of a second proteinase of cellular origin. We present evidence that translation of poliovirus proteinase 2A sequences in vitro activates p220 cleavage. We have also aligned published picornavirus 2A amino acid sequences for maximum homology, and we show that the picornaviruses can be divided into two classes based on the presence or absence of a highly conserved 18-amino acid sequence in the carboxy-terminal portion of 2A. This conserved 2A sequence is homologous with the active site of the cysteine proteinase 3C common to all picornaviruses. We show that picornaviruses which contain the putative 2A active site sequence (e.g., enteroviruses and rhinoviruses) will induce cleavage of p220 in vivo. Conversely, we show that two cardioviruses (encephalomyocarditis virus and Theiler's encephalomyelitis virus) do not encode this putative proteinase sequence in the 2A region and do not induce cleavage of p220 in vivo. The foot-and-mouth disease virus (FMDV) 2A sequence represents an apparent deletion and consists of only 16 amino acids, most homologous with the carboxy terminus of the cardiovirus 2A sequence. It does not contain the putative cysteine proteinase active site. However, FMDV infection induces complete cleavage of BK cell p220, and translation of FMDV RNA in vitro induces an activity that cleaves HeLa cell p220. The data predict that an alternate FMDV viral protease is responsible for the induction of p220 cleavage.
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PMID:Relationship of p220 cleavage during picornavirus infection to 2A proteinase sequencing. 284 33

Sequence analysis of VP1 in the DA strain of Theiler's murine encephalomyelitis viruses (TMEV) showed that 13 of the first 23 N-terminal amino acids were identical to those in the corresponding protein of encephalomyocarditis virus. There was little similarity to the corresponding VP1 sequences of poliovirus types 1, 2 and 3, coxsackievirus B3, human rhinoviruses 2 and 14, human hepatitis A virus or foot-and-mouth disease virus. These results, as well as serological relationships detected by immunoblotting, suggest that the TMEV are more closely related to the cardioviruses than to the enteroviruses with which they are presently classified. This newly recognized relationship suggests potential for recombinant infectious cDNA studies between TMEV and cardioviruses.
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PMID:Relationship of Theiler's murine encephalomyelitis viruses to the cardiovirus genus of picornaviruses. 303 22

Statistical analyses of RNA folding in 5' nontranslated regions (5'NTR) of encephalomyocarditis virus, Theiler's murine encephalomyelitis virus, foot-and-mouth disease virus, and hepatitis A virus indicate that two highly significant folding regions occur in the 5' and 3' portions of the 5'NTR. The conserved tertiary structural elements are predicted in the unusual folding regions (UFR) for these viral RNAs. The theoretical, common structural elements predicted in the 3' parts of the 5'NTR occur in a cis-acting element that is critical for internal ribosome binding. These structural motifs are expected to be highly significant from extensive Monte Carlo simulations. Nucleotides (nt) in the conserved single-stranded polypyrimidine tract for these RNAs are involved in a distinctively tertiary interaction that is located at about 15 nt prior to the initiator AUG. Intriguingly, the proposed common tertiary structure in this study shares a similar structural feature to that proposed in human enteroviruses and rhinoviruses. Based on these common structural features, plausible base pairing models between these viral RNAs and 18 S rRNA are suggested, which are consistent with a general mechanism for regulation of internal initiation of cap-independent translation.
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PMID:Conserved tertiary structural elements in the 5' nontranslated region of cardiovirus, aphthovirus and hepatitis A virus RNAs. 838 42

The foot-and-mouth disease virus (FMDV) leader coding region (Lb) was cloned into a full-length cDNA of the DA strain of Theiler's murine encephalomyelitis virus (TMEV) replacing the complete L coding region of TMEV. This construct, pDAFSSC1-Lb, was engineered to contain cleavage sites, at the 3' end of the Lb coding region, for both the FMDV Lb and the TMEV 3C proteases. Transcripts derived from this construct were translated in a cell-free system. Analysis of the translation products showed efficient synthesis and processing of TMEV structural and nonstructural proteins as well as a major band that comigrated with FMDV Lb and was reactive with Lb antiserum. A small plaque virus was recovered from BHK-21 cells transfected with RNA derived from pDAFSSC1-Lb. RT-PCR of RNA isolated from DAFSSC1-Lb virus demonstrated a product corresponding in size and sequence to FMDV Lb. DAFSSC1-Lb virus grew slower than parental virus, DAFSSC1, and to a lower titer. The pattern of viral proteins synthesized in DAFSSC1-Lb virus-infected cells was very similar to the pattern in DAFSSC1 virus-infected cells except that significant amounts of FMDV Lb were produced. In addition, extracts from DAFSSC1-Lb-virus-infected cells cleaved an exogenous source of the translation initiation factor, p220, while DAFSSC1-virus-infected extracts did not. Chimeric viruses that contain coding regions from different picornaviral genera may be valuable tools in investigating the function of particular viral proteins and in studying disease pathogenesis.
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PMID:Construction of a chimeric Theiler's murine encephalomyelitis virus containing the leader gene of foot-and-mouth disease virus. 894 32

Mutant forms of the encephalomyocarditis virus (EMCV) internal ribosome entry site (IRES) have been produced and shown to be severely defective in directing internal initiation of protein synthesis within cells using the vaccinia/T7 RNA polymerase system. Mutants in different regions of the IRES were complemented in trans by coexpression of the intact EMCV IRES but not by coexpression of the related IRES elements from Theiler's murine encephalomyelitis virus (another cardiovirus) or from foot-and-mouth disease virus. Distinct, truncated regions of the EMCV IRES, insufficient to direct internal initiation, were also shown to complement defective EMCV IRES elements. It was necessary for the complementing molecule, whether truncated or full length, to be expressed in the positive sense orientation. RT-PCR analysis provided no support for the idea that any recombination event was responsible for the complementation. The data suggest that multiple activities are performed by distinct functional entities within the IRES in the process of internal initiation of protein synthesis. At least some of these different functions may be achieved by different molecules acting in trans.
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PMID:Complementation of defective picornavirus internal ribosome entry site (IRES) elements by the coexpression of fragments of the IRES. 900 58

The primary 2A/2B polyprotein cleavage of aphtho-and cardioviruses is mediated by their 2A proteins cleaving C-terminally. Whilst the aphthovirus 2A region is only 16 aa (possibly 18 aa) long, the cardiovirus 2A protein is some 150 aa. We have previously shown that foot-and-mouth disease virus (FMDV) 2A is able to mediate cleavage in an artificial (chloramphenicol acetyltransferase/FMDV 2A/beta-glucuronidase [CAT-2A-GUS]) polyprotein system devoid of any other FMDV sequences with high (approximately 85%), although not complete, cleavage. In this paper we show that insertion of upstream FMDV capsid protein 1 D sequences increases the activity. In addition, we have demonstrated that the cardiovirus Theiler's murine encephalomyelitis virus(TME) 2A protein, when linked to GUS in a single ORF, is able to cleave at its own C terminus with high efficiency--if not completely. The C-terminal 19 aa of TME 2A, together with the N-terminal proline residue of protein 2B, were inserted into the CAT/GUS artificial polyprotein system (in a single ORF). This recombinant [CAT-deltaTME2A-GUS] polyprotein was able to mediate cleavage with high (approximately 85%) efficiency--directly comparable to the activity observed when FMDV 2A was inserted. A similar insertion into [CAT-GUS] of the C-terminal 19 aa of the cardiovirus encephalomyocarditis virus (EMC) 2A, together with the N-terminal proline residue of protein 2B, produced a [CAT-delta EMC2A-GUS] polyprotein which also mediated cleavage at approximately 85%. Analysis of the products of expression of these artificial polyproteins in a prokaryotic translation system did not, apparently, reveal any GUS cleavage product.
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PMID:The cleavage activities of aphthovirus and cardiovirus 2A proteins. 901 Feb 80

The translational control involving internal ribosome binding occurs in poliovirus (PV), human rhinoviruses (HRV), encephalomyocarditis virus (EMCV), foot-and-mouth disease virus (FMDV), and hepatitis A virus (HAV). Internal ribosome binding utilizes cis-acting genetic elements of approximately 450 nucleotides (nt) termed the internal ribosome entry sites (IRES) found in these picornaviral 5'-untranslated region (5'UTR). Although these IRES elements are quite different in their primary sequence, a similar folding structure with a conserved 3' structural core exists in the IRES. Phylogenetic analysis and RNA folding of the 5' UTR of picornaviruses, including PV types 1-3, coxsackievirus types A and B, swine vesicular disease virus, echoviruses, enteroviruses (human and bovine), HRV, HAV, EMCV, mengovirus, Theiler's murine encephalomyelitis viruses, FMDV, and equine rhinoviruses, indicates that the predicted conserved structural core is indeed a general structural feature for all members of the picornavirus family. The evolution of a common structural core likely occurred by the gradual addition or deletion of structural domains and elements to preserve a similar tertiary structure that facilitates the utilization of the IRES in specific host-cell environments.
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PMID:Evolution of a common structural core in the internal ribosome entry sites of picornavirus. 956 89

During an outbreak of hand-foot-mouth disease caused by enterovirus 71 (EV-71) in 1997, 4 children presented with sudden cardiopulmonary collapse and minimal neurologic features. All children received cardiopulmonary resuscitation but died within a few hours of admission. Postmortem studies showed infection by EV-71 with extensive damage to the medulla and pons. We postulate an etiologic link between EV-71 and brainstem encephalomyelitis as the cause of pulmonary edema and death.
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PMID:Fatal enterovirus 71 encephalomyelitis. 984 48

Cap-independent translation initiation on picornavirus mRNAs is mediated by an internal ribosomal entry site (IRES) in the 5' untranslated region (5' UTR) and requires both eukaryotic initiation factors (eIFs) and IRES-specific cellular trans-acting factors (ITAFs). We show here that the requirements for trans-acting factors differ between related picornavirus IRESs and can account for cell type-specific differences in IRES function. The neurovirulence of Theiler's murine encephalomyelitis virus (TMEV; GDVII strain) was completely attenuated by substituting its IRES by that of foot-and-mouth disease virus (FMDV). Reconstitution of initiation using fully fractionated translation components indicated that 48S complex formation on both IRESs requires eIF2, eIF3, eIF4A, eIF4B, eIF4F, and the pyrimidine tract-binding protein (PTB) but that the FMDV IRES additionally requires ITAF(45), also known as murine proliferation-associated protein (Mpp1), a proliferation-dependent protein that is not expressed in murine brain cells. ITAF(45) did not influence assembly of 48S complexes on the TMEV IRES. Specific binding sites for ITAF(45), PTB, and a complex of the eIF4G and eIF4A subunits of eIF4F were mapped onto the FMDV IRES, and the cooperative function of PTB and ITAF(45) in promoting stable binding of eIF4G/4A to the IRES was characterized by chemical and enzymatic footprinting. Our data indicate that PTB and ITAF(45) act as RNA chaperones that control the functional state of a particular IRES and that their cell-specific distribution may constitute a basis for cell-specific translational control of certain mRNAs.
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PMID:A cell cycle-dependent protein serves as a template-specific translation initiation factor. 1095 Aug 67

We report a fatal case of enterovirus type 71 (EV 71) infection in an 8-year-old girl during a summer outbreak of hand, foot, and mouth disease in 1998 in Taiwan. The clinical course was rapidly progressive, with manifestations of hand, foot, and mouth disease, aseptic meningitis, encephalomyelitis, and pulmonary edema. The patient died 24 hours after admission. Postmortem study revealed extensive inflammation in the meninges and central nervous system and marked pulmonary edema with focal hemorrhage. Brain stem and spinal cord were most severely involved. The inflammatory infiltrates consisted largely of neutrophils involving primarily the gray matter with perivascular lymphocytic cuffing, and neuronophagia. The lungs and heart showed no evidence of inflammation. EV 71 was isolated from the fresh brain tissues and identified by immunofluorescence method with type-specific EV 71 monoclonal antibody. It was also confirmed by neutralization test and reverse-transcriptase polymerase chain reaction with sequence analysis. The present case was the first example in which EV 71 was demonstrated to be the causative agent of fatal encephalomyelitis during its epidemic in Taiwan.
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PMID:Acute encephalomyelitis during an outbreak of enterovirus type 71 infection in Taiwan: report of an autopsy case with pathologic, immunofluorescence, and molecular studies. 1110 77


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