Parechovirus

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Virion

Morphology:	Icosahedral
Envelope:	No
Diameter (nm):	28
Length (nm):	–
Structural components:	RNA, capsid
Buoyant density (g/mL):	1.36
Buoyant density method:	CsCl gradient
Lipid composition:	None
Additional information:	None

Genome

Nucleic Acid:	RNA
Strandedness:	Single-stranded
Polarity:	Positive-sense
Configuration:	Linear
Segment organization:	Segment no. 1 (kb):	7.33
	One segment(s):	7.33 (kb) total (calculated)
G + C content (%):	39.1
mRNA transcripts:	1
Open reading frames:	1
Additional information:	A single polyprotein is encoded and this is cleaved by virus proteases to give the final proteins (probably 10)

Replication

Entry mechanism:	Interactions between integrins avb1/avb3/avb6/avb8 and the virus RGD motif; subsequent endocytosis
Site of transcription:	n/a
Transcriptase:	n/a
Site of genome replication:	Cytoplasm, involving perinuclear replication complexes
Replicase:	Virus-encoded RNA-dependent RNA polymerase
Replication intermediate:	Negative sense RNA
Site of virion assembly:	Cytoplasm
Egress mechanism:	Cell lysis
Additional information:	Entry mechanism of non-RGD containing viruses is not known

History

Year of event	Event	References
1956	First isolation of human parechovirus 1 and 2 (then called echoviruses 22 and 23, respectively)	Wigand R, Sabin AB (1961) Arch Gesamte Virusforsch 11:224–247
1961	Distinctive cellular pathology of human parechoviruses compared to other enterovirus genus members described	Shaver DN et al (1961) Proc Soc Exp Biol Med 106:648–652
1974	Distinctive cellular effects of human parechovirus 1 observed by electron microscopy	Jamison RM (1974) Arch Gesamte Virusforsch 44:184–194
1990	Human parechoviruses not recognized by enterovirus-specific DNA probes	Auvinen P, Hyypiä T (1990) J Gen Virol 71:2133–2139
1992	Complete sequence of human parechovirus 1 reveals it belongs to a new genetic group of Picornaviridae	Hyypiä T et al (1992) Proc Natl Acad Sci USA 89:8847–8851
1994	Molecular analysis of human parechoviruses reveals further distinctive features, such as lack of VP0 cleavage	Stanway G et al (1994) J Virol 68:8232–8238
1998	Strain of human parechovirus 2 sequenced	Ghazi F et al (1998) J Gen Virol 79:2641–2650
1998	Strain of human parechovirus 2 (later designated human parechovirus 5) sequenced	Oberste MS et al (1998) Virus Res 56:217–223
1999	Viruses related to parechoviruses isolated from rodents	Niklasson B et al (1999) Virology 255:86–93
1999	Human parechoviruses officially removed from Enterovirus genus and now are type species of Parechovirus genus	King AMQ et al (1999) In: Van Regenmortel et al (eds) Virus taxonomy. Seventh Report of the International Committee for the Taxonomy of Viruses, Academic Press
2000	Parechovirus 2A shown to be distinct from other picornavirus 2As and related to cellular proteins involved in proliferation	Hughes PJ, Stanway G (2000) J Gen Virol 81:201–207
2001	Infectious clone of human parechovirus 1 produced	Boonyakiat et al (2001) J Virol 75:10000–10004
2004	A third type of human parechovirus identified and the genomic sequence revealed the lack of the RGD motif thought to be involved in receptor binding	Ito M et al (2004) J Gen Virol 85:391–398
2004	Identification of 2A as an RNA binding protein	Samuilova O et al (2004) J Biol Chem 279:37822–37831
2006	Human parechovirus type 4 identified	Benschop KS et al (2006) Emerg Infect Dis 12:1572–1575
2007	Human parechovirus type 5 identified and new criteria for typing HPeVs defined	Al-Sunaidi M et al (2007) J Virol 81:1013–1021
2007	Human parechovirus type 6 identified	Watanabe K et al (2007) Emerg Infect Dis 13:889–895
2008	Recombination observed in human parechoviruses	Benschop KS et al (2008) J Gen Virol 89:1030–1035
2009	Human parechovirus type 7 identified	Li L et al (2009) Emerg Infect Dis 15:288–291
2009	Human parechovirus type 8 identified	Drexler JF et al (2009) Emerg Infect Dis 15:310–313
2010	Human parechovirus types 9–14 identified	Harvala H et al (2010) Curr Opin Infect Dis 23:224–230

Genus Members

Species name	Synonyms	Wild-type strains/isolates	Natural host range	Experimental host range	Membership status
Human parechovirus (HPeV)	Echovirus 22; Human parechovirus 1 Harris (HPeV1); Human parechovirus 2 Williamson (HPeV2); Human parechovirus 3 A308/99 (HPeV3); Human parechovirus 4 K251176-02 (HPeV4); Human parechovirus 5 CT86-6760 (HPeV5); Human parechovirus 6 NII561-2000 (HPeV6); Human parechovirus 7 PAK5045 (HPeV7); Human parechovirus 8 BR/217/2006 (HPeV8); Human parechovirus 9 BAN2004-10902 (HPeV9); Human parechovirus 10 BAN2004-10903 (HPeV10); Human parechovirus 11 BAN2004-10905 (HPeV11); Human parechovirus 12 BAN2004-10904 (HPeV12); Human parechovirus 13 BAN2005-10901 (HPeV13); Human parechovirus 14 451564 (HPeV14)		Humans	Mammals	Type species
Ljungan virus (LV)		145SL	Bank voles	Mammals	Approved member

Nucleotide Sequences

Genomic region	Species	Strain	Nucleotides	Access number	References
Complete genome	Human parechovirus	HPeV1 Harris	7,339	L02971	Hyypiä T et al (1992) Proc Natl Acad Sci USA 89:8847–8851
Complete genome	Human parechovirus	HPeV2 Williamson	7,348	AJ005695	Ghazi F et al (1998) J Gen Virol 79: 2641–2650
Complete genome	Human parechovirus	HPeV3 A308/99	7,321	AB084913	Ito M et al (2004) J Gen Virol 85:391–398
Complete genome	Human parechovirus	HPeV4 K251176-02	7,366	DQ315670	Benschop KS et al (2006) Emerg Infect Dis 12:1572–1575
Complete genome	Human parechovirus	HPeV5 CT86-6760	7,352	AF055846	Oberste MS et al (1998) Virus Res 56: 217–223
Complete genome	Human parechovirus	HPeV6 NII561-2000	7347	AB252582	Watanabe K et al (2007) Emerg Infect Dis 13:889–895
Complete genome	Human parechovirus	HPeV7 PAK5045	7,146	EU556224	Li L et al (2009) Emerg Infect Dis 15:288–291
Complete genome	Human parechovirus	HPeV8 BR/217/2006	7,353	EU716175	Drexler JF et al (2009) Emerg Infect Dis 15:310–313
VP1	Human parechovirus	HPeV14 451564	624	FJ373179	Benschop K et al (2008) J Clin Microbiol 46:3965–3970
Complete genome	Ljungan virus	145SL	7,592	AF327922	Lindberg AM, Johansson S (2002) Virus Res 85:61–70
Complete genome	Ljungan virus	174 F	7,591	AF327921	Lindberg AM, Johansson S (2002) Virus Res 85:61–70
Complete genome	Ljungan virus	87-012	7590	AF327920	Lindberg AM, Johansson S (2002) Virus Res 85:61–70
Complete genome	Ljungan virus	M1146	7,495	AF538689	Johansson ES et al (2003) J Gen Virol 84:837–844
Complete genome	Ljungan virus	64-7855	7,436	EU854568	Tolf C et al (2009) J Gen Virol 90:843–853

Proteins

Protein name	Protein name abbreviation	Number of amino acids	Molecular weight (kDa)	Time of expression	Accession numbers	Additional information
Capsid protein VP0	1AB	289	38.0	Not known	AAA72291	Not cleaved in parechoviruses
Capsid protein VP3	1 C	253	30.0	Not known	AAA72291	Has unique, highly basic N-terminal extension
Capsid protein VP1	1D	234	30.5	Not known	AAA72291	Has RGD motif in most human parechoviruses
Non-structural protein 2A	2A	147	17.4	Not known	AAA72291	Not a protease; may affect cell growth: RNA binding
Non-structural protein 2B	2B	122	14.2	Not known	AAA72291	Affects membrane permeability
Non-structural protein 2 C	2 C	329	38.2	Not known	AAA72291	Function unknown, but may be a helicase
Non-structural protein 3A	3A	117	13.5	Not known	AAA72291	Probably involved in RNA replication
VPg	3B	20	2.3	Not known	AAA72291	Attached to 5′ terminus of genomic RNA; primer for RNA replication
Protease 3 Cpro	3 C	200	23.2	Not known	AAA72291	Probably responsible for all polyprotein cleavage events
RNA-dependent RNA polymerase 3Dpol	3D	469	53.8	Not known	AAA72291	Performs synthesis of positive and negative RNA strands

Biology

Species	Permissive cell lines	Tissue tropism	Cytopathic effects	Additional information
Human parechovirus	GMK; A549; RD; avb6/ avb8-transfected SW480 cells	Respiratory and gastrointestinal tracts, CNS	Detachment and lysis of infected cells in culture	Changes to nucleus sometimes reported

Diseases

Disease	Causative agent	Affected organisms	Disease characteristics	Transmission route/vector	Treatment	Geographic distribution
Diarrhea	Human parechoviruses	Humans	Usually seen in young children	Fecal-oral	Palliative	World-wide
Respiratory disease	Human parechoviruses	Humans	Usually seen in young children	Unknown	Palliative	World-wide
Infections of CNS	Human parechoviruses	Humans	Paralysis and encephalitis reported	Probably fecal-oral	Palliative	World-wide

Vector Constructs

Vector name	Backbone strain	Application	Insertion capacity (kb)	Additional information	Reference
pHPeV1	Human parechovirus 1 strain Harris	Cloning	N/A	Complete, infectious cDNA copy of virus genome	Boonyakiat et al (2001) J Virol 75:10000–10004

Parechovirus. Fig. 1

Picture of purified virions, negatively stained with uranyl acetate, taken at 120 kV with a Philips CM120 microscope. Length of bar (nm): 50 (Picture kindly provided by Li Xing and Holland Cheng)

Organization of the parechovirus genome, as exemplified by Human parechovirus 1. Fig. 2

Untranslated regions are shaded grey; the regions of the single open reading frame encoding the final proteins are labeled 1AB-3D; protein functions, where known, are indicated below the map