Genus: Enterovirus


Genus: Enterovirus

Virion

Morphology

Crystal structures of many enteroviruses have been resolved (Enterovirus A: coxsackie virus (CV)-A7, CV-A16, enterovirus (EV)-A71; Enterovirus B: CV-A9, CV-B3, E-1, E-7, E-11, E-12, swine vesicular disease virus (SVDV)-1; Enterovirus C: PV-1, PV-2, PV-3, CV-A21, CV-A24; Enterovirus D: EV-D68; Enterovirus E: EV-E; Rhinovirus A: RV-A1, RV-A2, RV-A16; Rhinovirus B: RV-B14; Rhinovirus C: RV-C15). CPs 1B, 1C and 1D of the human enteroviruses and rhinoviruses are among the largest in the family (VP1-3 chain lengths, 238-302 aa), and this is reflected in the typically long inter-β-strand loops, the larger than average thickness of the capsid wall (46 Å), and a surface relief that is strongly pronounced compared to most other picornaviruses. Encircling a raised area at the 5-fold axis is a 25 Å deep groove, or "canyon", into which the cellular receptor for poliovirus binds. The binding site for the pocket factor lies beneath the floor of this canyon within the 1D β-barrel. Virions can be converted by a variety of treatments (gentle heating, binding to receptor, or some neutralizing antibodies) to altered ('A') particles of 135S which lack 1A (VP4) and possess altered antigenicity.

Physicochemical and physical properties

Acid stability is variable. The virions of most enterovirus species are stable at pH 3.0, while those of the rhinovirus species are unstable below pH 5-6. Similarly, the buoyant density in CsCl of the enterovirus virions is 1.30-1.34 g cm-3, while the rhinoviruses range from 1.38 to 1.42 g cm-3. Sometimes a small proportion (about 1% of the population) of heavy particles (density: 1.43 g cm-3) can be observed in the enteroviruses. Empty capsids are often observed in virus preparations.

Nucleic acid

Length of genome (Kitamura et al., 1981, Racaniello and Baltimore 1981, van der Werf et al., 1981): c. 7,100-7,450 nt (5'-UTR: 610-822 nt; ORF: 6,417-6,645 nt; 3'-UTR: 37-99 nt). The genome contains a type I IRES and no poly(C) tract. The cre is located in 2C (EV-A viruses, EV-B, EV-C and EV-D viruses) or 2A (RV-A viruses) or 1D (RV-B viruses) or 1B (EV-C viruses). Sequence identities for different enteroviruses, or between enteroviruses and rhinoviruses are more than 50% over the genome as a whole although it may be greater or less than this for particular genomic regions. The 5′-UTR of human rhinoviruses is shorter (ca. 650 nt) than that of enteroviruses, due to a deletion of approximately 100 nt between the IRES and the translation start site. Some EV-C viruses and EV-D viruses also have smaller deletions in this region. EV-E and EV-F viruses have a non-perfect duplication of the first ~100 nucleotides allowing the formation of a second clover-leaf-like RNA structure. EV-G viruses have an insertion of about 30 nt approximately 65 nt from the 5' end of the genome resulting in a longer stem-loop D in the cloverleaf structure. Varying size deletions in the same region have been observed in some of the human enteroviruses. 

Genome organization and replication

Genome layout:

VPg+5'UTRIRES-I[1A-1B-1C-1D/2Apro-2B-2C/3A-3B-3C-3D]3'UTR-poly(A)

The deduced polyprotein of enteroviruses ranges from 2,138-2,214 amino acids. Genomes encode no L protein. 2A protein has proteinase activity (2Apro), which is related to the family of small bacterial serine proteases, cleaves the polyprotein at its own N-terminus. Certain hydrophobic molecules that bind to the capsid in competition with pocket factor exert a powerful antiviral action by interfering with receptor binding and/or uncoating. Antiviral, pocket-binding drugs have been described.

Antigenicity

Approximately 75 enterovirus serotypes and 100 rhinovirus serotypes have been classified by means of neutralization of infectivity.

Biology

Viruses multiply primarily in the gastrointestinal tract or the upper respiratory tract or sometimes both, but they can also multiply in other tissues, e.g., nerve, muscle, etc. Infection may frequently be asymptomatic. Clinical manifestations include common cold, mild meningitis, encephalitis, myelitis, myocarditis and conjunctivitis. Swine vesicular disease virus is a variant of coxsackievirus B5 and causes a vesicular disease in pigs clinically indistinguishable from foot-and-mouth disease (genus Aphthovirus) and vesicular disease in pigs caused by Seneca Valley virus (genus Senecavirus). Cap-dependent translation of host mRNA is inhibited by 2Apro, which cleaves the host eukaryotic initiation factor 4G (eIF-4G). Many different cell surface molecules, many of them uncharacterized, serve as viral receptors. Well characterized receptor/virus interactions include poliovirus receptor (PVR) / polioviruses, coxsackievirus-adenovirus receptor (CAR) / coxsackie B viruses, inter-cellular adhesion molecule 1 (ICAM-l) / major-group rhinoviruses and some members of the Enterovirus C species, low-density lipoprotein receptor (LDLR) / minor-group rhinoviruses, decay-accelerating factor (DAF) / various enteroviruses, integrin VLA-2 / echovirus 1, and sialic acid / enterovirus D70. Poliovirus type 2 of Enterovirus C species is believed to have been eradicated by humans from circulation in human populations.

Species demarcation criteria

Members of a species of the genus Enterovirus:

  • share greater than 70% aa identity in the polyprotein,
  • share greater than 60% aa identity in P1,
  • share greater than 70% aa identity in the non-structural proteins 2C + 3CD
  • utilize a limited range of host cell receptors,
  • infect a limited natural host range,
  • have a genome base composition (G+C) which varies by no more than 2.5%,
  • share a significant degree of compatibility in proteolytic processing, replication, encapsidation and genetic recombination.
  • share a common genome organization.

The divergence (number of differences per site between sequences) of known Enterovirus species ranges from 0.29-0.59 for P1 and 0.1-0.48 for 3CD.

More than 300 virus types have been characterized genetically by phylogenetic clustering (Oberste et al., 1999, Palmenberg et al., 2009, Simmonds et al., 2010, McIntyre et al., 2013). Enterovirus A: 25 types, Enterovirus B: 63 types, Enterovirus C: 23 types, Enterovirus D: 5 types, Enterovirus E: 5 types, Enterovirus F: 7 types, Enterovirus G: 20 types, Enterovirus H: 1 type, Enterovirus I: 1 type, Enterovirus J: 6 types, Rhinovirus A: 80 types, Rhinovirus B: 32 types, Rhinovirus C: 55 types; at least 3 types await classification. 

Member Species

SpeciesVirus name(s)Exemplar isolateExemplar accession numberExemplar RefSeq numberAvailable sequenceOther isolatesOther isolate accession numbersVirus Abbreviation(s)Isolate Abbreviation
Enterovirus Acoxsackievirus A2FleetwoodAY421760Complete genomeCV-A2
Enterovirus Bcoxsackievirus B3M88483Complete genomeCV-B3
Enterovirus Cpoliovirus 1MahoneyV01149NC_002058Complete genomePV-1
Enterovirus Denterovirus D68FermonAY426531Complete genomeEV-D68
Enterovirus Eenterovirus E; bovine enterovirus 1VG-5-27D00214NC_001859Complete genomeEV-E
Enterovirus Fenterovirus F, bovine enterovirus 2BEV-261, M2, RM2DQ092770NC_021220Complete genomeEV-F
Enterovirus Genterovirus G1, porcine enterovirus 9UKG-410-73AF363453NC_004441Complete genomeEV-G
Enterovirus Henterovirus H; simian enterovirus1715UWBAF326759Complete genomeEV-H
Enterovirus Ienterovirus I, dromedary camel enterovirus19CCKP345887Complete genomeEV-I
Enterovirus Jenterovirus JSV6-1631AF326766NC_010415Complete genomeEV-J
Enterovirus Kenterovirus K1Rodent/Ee/PicoV/NX2015KX156158Complete coding genomeEV-K
Enterovirus Lenterovirus L1Macaca mulatta/SEV-gx/2014/ChinaKU587555NC_029905Complete genomeEV-L
Rhinovirus Arhinovirus A1VR-1559FJ445111Complete genomeRV-A1
Rhinovirus Brhinovirus B3DQ473485Complete genomeRV-B3
Rhinovirus Crhinovirus C1NAT001EF077279Complete genomeRV-C1

Virus names, the choice of exemplar isolates, and virus abbreviations, are not official ICTV designations.
Download GenBank/EMBL query for sequences listed in the table here.

Certain viruses initially reported as novel echoviruses (E) were later shown to have been misidentified. Thus E-8 is the same serotype as E-1, E-10 is now reovirus 1, E-28 is now human rhinovirus 1A, E-22 is now human parechovirus 1, E-23 is now human parechovirus 2. Similarly, CV-A23 is the same serotype as E-9, and CV-A15 is the same serotype as CV-A11, and CV-A18 is the same as serotype as CV-A13. Hepatitis A virus (genus Hepatovirus) was previously assigned the name enterovirus 72. Human rhinovirus 87 has been found to be a strain of EV-D68. A number of simian viruses (SV), previously listed as tentative members of the genus, have been moved to the genus Sapelovirus, species Sapelovirus B and renamed simian sapelovirus (SSV) 1 (formerly SV2), SSV-2 (formerly SV49) and SSV-3 (formerly SV16, SV18, SV42, SV44 and SV45). Simian agent 4 (SA4), SV4, SV28 and A2-plaque virus have been assigned to the species Enterovirus H. Simian enteroviruses N125 and N203 have been placed into a new type, EV-108, which has been assigned to the species Enterovirus J, along with EV-103 and SV6. Type SV-47 remains unassigned to a species. Porcine enteroviruses (PEV) belonging to CPE group I (types 1-7 and 11-13) have been moved to the genus Teschovirus, species Teschovirus A, and renamed porcine teschovirus (PTV) 1-10. Members of the defunct species Porcine enterovirus A (PEV type 8; CPE group II) has been moved to the genus Sapelovirus and renamed Sapelovirus A (serotype porcine sapelovirus 1). The defunct species Porcine enterovirus B (PEV types 9, 10; CPE group III) has been renamed Enterovirus G.

Derivation of names

Entero: from Greek enteron, 'intestine'

Related, Unclassified Viruses

Virus name

Accession number

Virus abbreviation

Simian enterovirus gx [gx/China/2014]

KU587555

SEV-gx

Rodent picornavirus [rodent/Ee/PicoV/NX2015

KX156158

 

Rodent picornavirus [rodent/McPicoV/Tibet2015]

KX156159

 

Virus names, the choice of exemplar isolates, and virus abbreviations, are not official ICTV designations.
Download GenBank/EMBL query for sequences listed in the table here.