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The crystal structures of mengovirus (Cardiovirus A) and TMEV and Saffold virus 3 (Cardiovirus B) have been resolved [{Grant et al., 1992:1549565RJOHTXGrant et al., 1992, Three-dimensional structure of Theiler virus, Proceedings of the National Academy of Sciences, USA 89, 6, 2061-5RJOMREFKrishnaswamy and Rossmann 1990:2156078RJOHTXKrishnaswamy and Rossmann 1990, Structural refinement and analysis of Mengo virus, J Mol Biol, 211, 4, 803-44}]. Empty capsids are seen only rarely, if ever. When compared by mean wall thickness, surface unevenness, and chain length of the major proteins, the cardiovirus capsid is intermediate between the enteroviruses and aphthoviruses. In place of a continuous, circular canyon seen in enteroviruses, is a five-fold repeated pit. There is no pocket factor.
Virion buoyant density in CsCl is 1.33-1.34 g cm-3. Virions are moderately stable to acidic pH.
Length of genome [{Bae et al., 1989:2541543RJOHTXBae et al., 1989, Genomic differences between the diabetogenic and nondiabetogenic variants of encephalomyocarditis virus, Virology, 170, 1, 282-7RJOMREFOhara et al., 1988:2834872RJOHTXOhara et al., 1988, Molecular cloning and sequence determination of DA strain of Theiler's murine encephalomyelitis viruses, Virology, 164, 1, 245-55RJOMREFDuke et al., 1992:1310768RJOHTXDuke et al., 1992, Sequence and structural elements that contribute to efficient encephalomyocarditis virus RNA translation, J Virol, 66, 3, 1602-9RJOMREFLaw and Brown 1990:2251141RJOHTXLaw and Brown 1990, The complete nucleotide sequence of the GDVII strain of Theiler's murine encephalomyelitis virus (TMEV), Nucleic Acids Res, 18, 22, 6707-8}]: c. 7,730-8,530 nt (5'-UTR: up to 1,451 nt, ORF: 6,879-6,924 nt, 3'-UTR: 121-144 nt). EMC viruses have a poly(C) tract of variable length (usually 80-250 nt) about 150 nt from the 5′-terminus of the viral RNA, while the other cardioviruses lack this feature. EMC viruses have two pseudoknots 5′ to their poly(C) tracts. The IRES is of type II. The cre is located in the 1B region of both EMCV-1 and TMEV. The nt sequence identity over the entire genome for different species of the genus Cardiovirus is more than 50% (e.g. TMEV has 54% nt sequence identity to EMCV).
The cardiovirus L protein is a unique picornavirus protein with Zn-finger domain (C-x-H-x6-C-x2-C) playing key roles in (i) the regulation of virus translation, (ii) phosphorylation of nucleoporins, and (iii) inhibition of interferon synthesis. It binds the cellular Ran-GTPase. The cardiovirus 2A protein contains an NPG↓P motif and additional domains facilitating nucleolar localization, rRNA binding, and inhibition of cap-dependent cellular mRNA translation.
Genome layout
Cardiovirus A, B: VPg+5'UTRIRES-II[L/1A-1B-1C-1D-2Anpgp/2B-2C/3A-3B-3C-3D]3'UTR-poly(A)
Cardiovirus C: VPg+5'UTRIRES-II[L/1A-1B-1C-1D/2A-2B-2C/3A-3B-3C-3D]3'UTR-poly(A)
The deduced polyproteins have lengths ranging from 2,292-2,307 aa. The viral genome encodes a leader (L) protein which lacks proteolytic activity. The 2A protein of members of the species Cardiovirus A and B has a length of c. 140 aa and causes NPG↓P-mediated polypeptide chain interruption at its C-terminus. The orthologous 2A protein of Boone cardioviruses (Cardiovirus C) is shorter (127 aa) and lacks an NPG↓P motif.
Four independent antigenic sites have been described. There is no evidence of an N-D conversion, nor of 'A' particles. The species Cardiovirus A consists of a two types [{*** 1949:18133621RJOHTXDick 1949, The relationship of Mengo encephalomyelitis, encephalomyocarditis, Columbia-SK and M.M. viruses, J Immunol, 62, 4, 375-86RJOMREFWarren et al., 1949:18133622RJOHTXWarren et al., 1949, The family relationship of encephalomyocarditis, Columbia-SK, M.M., and Mengo encephalomyelitis viruses, J Immunol, 62, 4, 387-98RJOMREFPhilipps et al., 2012:22824255RJOHTXPhilipps et al., 2012, Isolation and molecular characterization of a second serotype of the encephalomyocarditis virus, Vet Microbiol, 161, 1-2, 49-57}]. However, the species Cardiovirus B comprises 15 genetic types, Theiler’s murine encephalomyelitis virus (TMEV), Vilyuisk human encephalomyelitis virus (VHEV), thera virus (formerly named Theiler-like virus of rats), Saffold virus (SAFV) types 1 to 11, and genet fecal theilovirus (from Geneta geneta) [{Ohara et al., 1988:2834872RJOHTXOhara et al., 1988, Molecular cloning and sequence determination of DA strain of Theiler's murine encephalomyelitis viruses, Virology, 164, 1, 245-55RJOMREFPevear et al., 1988:2838951RJOHTXPevear et al., 1988, Insights into Theiler's virus neurovirulence based on a genomic comparison of the neurovirulent GDVII and less virulent BeAn strains, Virology, 165, 1, 1-12RJOMREFPevear et al., 1987:3033278RJOHTXPevear et al., 1987, Analysis of the complete nucleotide sequence of the picornavirus Theiler's murine encephalomyelitis virus indicates that it is closely related to cardioviruses, J Virol, 61, 5, 1507-16RJOMREFLiang et al., 2008:18815294RJOHTXLiang et al., 2008, Phylogenetic analysis of the species Theilovirus: emerging murine and human pathogens, J Virol, 82, 23, 11545-54RJOMREFOhsawa et al., 2003:12784854RJOHTXOhsawa et al., 2003, Genetic analysis of a Theiler-like virus isolated from rats, Comp Med, 53, 2, 191-6RJOMREFJones et al., 2007:17460053RJOHTXJones et al., 2007, Discovery of a novel human picornavirus in a stool sample from a pediatric patient presenting with fever of unknown origin, J Clin Microbiol, 45, 7, 2144-50RJOMREFChiu et al., 2008:18768820RJOHTXChiu et al., 2008, Identification of cardioviruses related to Theiler's murine encephalomyelitis virus in human infections, Proceedings of the National Academy of Sciences, USA 105, 37, 14124-9RJOMREFAbed and Boivin 2008:18439376RJOHTXAbed and Boivin 2008, New Saffold cardioviruses in 3 children, Canada, Emerg Infect Dis, 14, 5, 834-6RJOMREFBodewes et al., 2014:24886057RJOHTXBodewes et al., 2014, Viral metagenomic analysis of *** of wild small carnivores, Virol J, 11, 89}]. There is no cross-neutralization between TMEV and VHEV; however, the antigenic relationships between these and thera, saffold and genet fecal theiloviruses is presently not known. Species Cardiovirus C consists of two types.
Encephalomyocarditis viruses have been isolated from over 30 host species including mammals, birds and invertebrates. Clinical manifestations include encephalitis and myocarditis in mice and many other animals. TMEV can be divided into two biological subgroups which both infect mice; one causes an acute and fatal polioencephalomyelitis and the other causes a chronic persistent demyelinating infection of the white matter. VHEV was isolated (in mice) from a person suffering from a degenerative neurological disease (Vilyuisk encephalitis). Since then, however, the virus has been extensively passaged in mice during the 1950’s and it is not clear if it is of human or mouse origin. Thera virus has been isolated from clinically normal rats. Saffold viruses have been isolated from humans, especially children and have been associated with both respiratory disease and gastroenteritis. Boone cardioviruses were detected in specimens of rats. Cardiovirus infection does not cause cleavage of the host eIF-4G. The cellular receptor used by EMCV to attach to murine vascular endothelial cells has been identified as VCAM-1. However, in human cell lines an as yet unidentified sialoglycoprotein(s) is used. EMCV binds to human erythrocytes via glycophorin A. Low-neurovirulence TMEV’s use sialic acid to attach to mammalian cells, while glycosaminoglycan heparan sulphate is involved in the attachment of high-neurovirulence TMEV’s.
Members of a species of the genus Cardiovirus:
The divergence (number of differences per site between sequences) of known Cardiovirus species ranges from 0.38-0.51 for P1 and 0.4-0.47 for 3CD.
Cardio-: from Greek kardia, "heart"