Enterovirus (taxid:12059)

Enterovirus is a genus of ssRNA+ viruses in the Picornaviridae family that infect mammals. In humans, these viruses cause gastroenteritis (enteroviruses) or respiratory infections (rhinoviruses).

NB. Rhinoviruses are merged into enterovirus genus

VIRION

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Non-enveloped, spherical, about 30 nm in diameter, T=pseudo3 icosahedral capsid surrounding the naked RNA genome. The capsid consists of a densely-packed icosahedral arrangement of 60 protomers, each consisting of 4 polypeptides, VP1, VP2, VP3 and VP4. VP4 is located on the internal side of the capsid.
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GENOME

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Monopartite, linear ssRNA(+) genome of 7.2-8.5 kb, polyadenylated, composed of a single ORF encoding a polyprotein. Viral genomic RNA has a viral protein (VPg) at its 5' end instead of a methylated nucleotide cap structure. The long UTR at the 5' end contains a type I internal ribosome entry site (IRES). The P1 region encodes the structural polypeptides. The P2 and P3 regions encode the nonstructural proteins associated with replication.

GENE EXPRESSION

The virion RNA is infectious and serves as both the genome and viral messenger RNA. The IRES allows direct translation of the polyprotein. The polyprotein is initially processed by the viral proteases into three precursor proteins, P1, P2, and P3. Precursor P1 is then proteolytically cleaved to yield the structural proteins. Precursors P2 and P3 are processed into replicase, VPg, and a number of proteins that modify the host cell, ultimately leading to cell lysis. Enterovirus A, B, E, F and G genomes and around half the enterovirus C genomes encode an upstream open reading frame (uORF).

ENZYMES

REPLICATION

poliovirus replication cycle

CYTOPLASMIC

  1. Attachement of the virus to host receptors mediates endocytosis of the virus into the host cell.
  2. The capsid undergoes a conformational change and releases VP4 that opens a pore in the host endosomal membrane and the viral genomic RNA penetrates into the host cell cytoplasm (the empty capsid remains intact).
  3. VPg is removed from the viral RNA, which is then translated into a processed polyprotein.
  4. Shutoff of cellular cap-dependent translation through the cleavage of translation initiation factors by viral protease.
  5. Replication occurs in viral factories made of membrane vesicles derived from the ER. A dsRNA genome is synthesized from the genomic ssRNA(+).
  6. The dsRNA genome is transcribed/replicated thereby providing viral mRNAs/new ssRNA(+) genomes.
  7. New genomic RNA is believed to be packaged into preassembled procapsids.
  8. Cell lysis and virus release.
  9. Maturation of provirions by an unknown host protease.

Host-virus interaction

Apoptosis modulation

Picornaviruses modulate host apoptosis .

Poliovirus infection activates the apoptotic pathway, involving mitochondrial damage, cytochrome c efflux, and consecutive activation of caspases (caspase-3 caspase and -9) , whereas antiapoptotic activity has been attributed to cardiovirus leader protein .

Modulation of apoptosis depends on the host cell-type and on the time the infection because of the presence of viral pro- and anti-apoptotic factors respectively at the beginning and at the end of the infectious cycle .

Autophagy modulation

Picornaviruses subvert the cell autophagic pathway to facilitates viral infection :

- Human rhinovirus 2 activates the autophagic pathway
- Coxsackievirus and poliovirus infection induces autophagy-like vesicles

Innate immune response inhibition

Picornaviruses inhibit the host IFN-mediated response by inactivating either MDA-5, RIG-I, MAVS or IRF-3:
- Coxsackievirus B3 cleaves and inhibits MAVS
- Enteroviruses cleave and inhibit RIG-I
- Poliovirus cleaves and inhibits MDA-5

Picornaviruses inhibit Toll-like receptor 3 mediated antiviral response as well:

- Coxsackievirus B 3C and enterovirus 71 proteases 3C cleave TRIF .

Host gene expression shutoff by virus

Enteroviruses inhibit host translation by cleaving PABP (coxsackievirus and poliovirus) , eIF5B and activating 4E-BP1 .

Poliovirus also inhibits host transcription by cleaving the TATA-binding protein .

HRV14, HRV16 and poliovirus inhibit host mRNA export as well .

Matching UniProtKB/Swiss-Prot entries

(all links/actions below point to uniprot.org website)

47 entries grouped by protein

3 entries

ORF2p protein

Select_allDeselect_all
ORF2P_POL1M
Poliovirus type 1 (strain Mahoney) reference strain
ORF2P_CXB3N
Coxsackievirus B3 (strain Nancy)
ORF2P_HE71B
Human enterovirus 71 (strain USA/BrCr/1970) (EV71) (EV-71)

44 entries

Genome polyprotein

Select_allDeselect_all
POLG_HRV8A
Human rhinovirus A serotype 89 (strain 41467-Gallo) (HRV-89) reference strain
POLG_BOVEV
Bovine enterovirus (strain VG-5-27) (BEV)
POLG_CX16G
Coxsackievirus A16 (strain G-10)
POLG_CX16T
Coxsackievirus A16 (strain Tainan/5079/98)
POLG_CXA21
Coxsackievirus A21 (strain Coe)
POLG_CXA24
Coxsackievirus A24 (strain EH24/70)
POLG_CXA9
Coxsackievirus A9 (strain Griggs)
POLG_CXB1J
Coxsackievirus B1 (strain Japan)
POLG_CXB2O
Coxsackievirus B2 (strain Ohio-1)
POLG_CXB3N
Coxsackievirus B3 (strain Nancy)
POLG_CXB3W
Coxsackievirus B3 (strain Woodruff)
POLG_CXB4E
Coxsackievirus B4 (strain E2)
POLG_CXB4J
Coxsackievirus B4 (strain JVB / Benschoten / New York/51)
POLG_CXB5P
Coxsackievirus B5 (strain Peterborough / 1954/UK/85)
POLG_CXB6S
Coxsackievirus B6 (strain Schmitt)
POLG_EC01F
Echovirus 1 (strain Human/Egypt/Farouk/1951) (E-1)
POLG_EC05N
Echovirus 5 (strain Noyce)
POLG_EC06C
Echovirus 6 (strain Charles)
POLG_EC09B
Echovirus 9 (strain Barty)
POLG_EC09H
Echovirus 9 (strain Hill)
POLG_EC11G
Echovirus 11 (strain Gregory)
POLG_EC12T
Echovirus 12 (strain Travis)
POLG_EC30B
Echovirus 30 (strain Bastianni)
POLG_HE701
Human enterovirus 70 (strain J670/71) (EV70) (EV-70)
POLG_HE71
Human enterovirus 71 (EV71) (EV-71)
POLG_HE71B
Human enterovirus 71 (strain USA/BrCr/1970) (EV71) (EV-71)
POLG_HE71M
Human enterovirus 71 (strain 7423/MS/87) (EV71) (EV-71)
POLG_HED68
Human enterovirus D68 (EV68) (EV-68)
POLG_HRV15
Human rhinovirus C (strain C15) (HRV-C15)
POLG_HRV16
Human rhinovirus 16 (HRV-16)
POLG_HRV1A
Human rhinovirus 1A (HRV-1A)
POLG_HRV1B
Human rhinovirus 1B (HRV-1B)
POLG_HRV2
Human rhinovirus 2 (HRV-2)
POLG_HRV3
Human rhinovirus 3 (HRV-3)
POLG_PEV9U
Porcine enterovirus 9 (strain UKG/410/73)
POLG_POL1S
Poliovirus type 1 (strain Sabin)
POLG_POL2L
Poliovirus type 2 (strain Lansing)
POLG_POL2W
Poliovirus type 2 (strain W-2)
POLG_POL32
Poliovirus type 3 (strain 23127)
POLG_POL3L
Poliovirus type 3 (strains P3/Leon/37 and P3/Leon 12A[1]B)
POLG_SVDVH
Swine vesicular disease virus (strain H/3 '76) (SVDV)
POLG_SVDVU
Swine vesicular disease virus (strain UKG/27/72) (SVDV)