Genus: Cardiovirus


Genus: Cardiovirus

Virion

Morphology

The crystal structures of mengovirus (Cardiovirus A), Theiler's murine encephalomyelitis virus (TMEV), and Saffold virus 3 (Cardiovirus B) have been resolved (Grant et al., 1992, Krishnaswamy and Rossmann 1990). 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.

Physicochemical and physical properties

Virion buoyant density in CsCl is 1.33-1.34 g cm-3. Virions are moderately stable to acidic pH.

Nucleic acid

Length of genome (Bae et al., 1989, Ohara et al., 1988, Duke et al., 1992, Law and Brown 1990): c. 7,730-8,530 nt (5'-UTR: up to 1,451 nt, ORF: 6,879-6,924 nt, 3'-UTR: 121-144 nt). Encepholomyocarditis (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 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).

Proteins

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 organization and replication

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.

Antigenicity

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 two types (Dick 1949, Warren et al., 1949, Philipps et al., 2012). 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, Pevear et al., 1988, Pevear et al., 1987, Liang et al., 2008, Ohsawa et al., 2003, Jones et al., 2007, Chiu et al., 2008, Abed and Boivin 2008, Bodewes et al., 2014). 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.

Biology

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.

Species demarcation criteria

Members of a species of the genus Cardiovirus:

  • share greater than 70% aa identity in the polyprotein,
  • share greater than 60% aa identity in P1,
  • share greater than 70% aa identity in 2C + 3CD,
  • share a natural host range,
  • share a common genome organization.

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.

Member species

SpeciesVirus name(s)Exemplar isolateExemplar accession numberExemplar RefSeq numberAvailable sequenceOther isolatesOther isolate accession numbersVirus abbreviationIsolate abbreviation
Cardiovirus Aencephalomyocarditis virus 1RueckertM81861NC_001479Complete genomeEMCV-1
Cardiovirus BTheiler's murine encephalomyeltits virusGDVIIX56019NC_001366Complete genomeTMEV
Cardiovirus CBoone cardiovirus rat/USA/2010JQ864242Complete coding genomeBCV

Virus names, the choice of exemplar isolates, and virus abbreviations, are not official ICTV designations.

Derivation of names

Cardio: from Greek kardia, "heart"