Introduction
Enteroviruses are a genus of positive-sense single-stranded RNA viruses associated with several human and mammalian diseases. Serologic studies have distinguished 71 human enterovirus serotypes on the basis of antibody neutralization tests. Additional antigenic variants have been defined within several of the serotypes on the basis of reduced or nonreciprocal cross-neutralization between variant strains. On the basis of their pathogenesis in humans and animals, the enteroviruses were originally classified into four groups, polioviruses, Coxsackie A viruses (CA), Coxsackie B viruses (CB), and echoviruses, but it was quickly realized that there were significant overlaps in the biological properties of viruses in the different groups. Enteroviruses isolated more recently are named with a system of consecutive numbers: EV68, EV69, EV70, EV71, etc.
Research Area
Capsid protein VP1:
Forms an icosahedral capsid of pseudo T=3 symmetry with capsid proteins VP2 and VP3 (By similarity).
The capsid is 300 Angstroms in diameter, composed of 60 copies of each capsid protein and enclosing the viral positive strand RNA genome (By similarity).
Capsid protein VP1 mainly forms the vertices of the capsid (By similarity).
Capsid protein VP1, together with VP2, interacts with host cell receptor SCARB2 to provide virion attachment to target host cells. This attachment induces virion internalization predominantly through clathrin-dependent endocytosis (PubMed:20956521).
After binding to its receptor, the capsid undergoes conformational changes (By similarity).
Capsid protein VP1 N-terminus (that contains an amphipathic alpha-helix) and capsid protein VP4 are externalized (By similarity).
Together, they shape a pore in the host membrane through which viral genome is translocated to host cell cytoplasm (By similarity).
Capsid protein VP2:
Forms an icosahedral capsid of pseudo T=3 symmetry with capsid proteins VP2 and VP3 (By similarity).
The capsid is 300 Angstroms in diameter, composed of 60 copies of each capsid protein and enclosing the viral positive strand RNA genome (By similarity).
Capsid protein VP2, together with VP1, interacts with host cell receptor SCARB2 to provide virion attachment to target host cells (By similarity).
Capsid protein VP3:
Forms an icosahedral capsid of pseudo T=3 symmetry with capsid proteins VP2 and VP3 (By similarity).
The capsid is 300 Angstroms in diameter, composed of 60 copies of each capsid protein and enclosing the viral positive strand RNA genome (By similarity).
Capsid protein VP4:
Lies on the inner surface of the capsid shell (By similarity).
After binding to the host receptor, the capsid undergoes conformational changes (By similarity).
Capsid protein VP4 is released, Capsid protein VP1 N-terminus is externalized, and together, they shape a pore in the host membrane through which the viral genome is translocated into the host cell cytoplasm (By similarity).
Capsid protein VP0:
Component of immature procapsids, which is cleaved into capsid proteins VP4 and VP2 after maturation (By similarity).
Allows the capsid to remain inactive before the maturation step (By similarity).
Protease 2A:
Cysteine protease that cleaves viral polyprotein and specific host proteins (By similarity).
It is responsible for the autocatalytic cleavage between the P1 and P2 regions, which is the first cleavage occurring in the polyprotein (By similarity).
Cleaves also the host translation initiation factor EIF4G1, in order to shut down the capped cellular mRNA translation (By similarity).
Inhibits the host nucleus-cytoplasm protein and RNA trafficking by cleaving host members of the nuclear pores (By similarity).
Counteracts stress granule formation probably by antagonizing its assembly or promoting its dissassembly (PubMed:30867299).
Cleaves and inhibits host IFIH1/MDA5, thereby inhibiting the type-I IFN production and the establishment of the antiviral state (PubMed:24390337).
Cleaves and inhibits host MAVS, thereby inhibiting the type-I IFN production and the establishment of the antiviral state (PubMed:24390337, PubMed:28253362).
Protein 2B:
Plays an essential role in the virus replication cycle by acting as a viroporin. Creates a pore in the host reticulum endoplasmic and as a consequence releases Ca2+ in the cytoplasm of infected cell (By similarity).
In turn, high levels of cytoplasmic calcium may trigger membrane trafficking and transport of viral ER-associated proteins to viroplasms, sites of viral genome replication (By similarity).
Activates also the mitochondrial apoptotic pathway by activating host BAX (PubMed:27558414).
Protein 2C:
Induces and associates with structural rearrangements of intracellular membranes. Displays RNA-binding, nucleotide binding and NTPase activities. May play a role in virion morphogenesis and viral RNA encapsidation by interacting with the capsid protein VP3.
Protein 3AB:
Localizes the viral replication complex to the surface of membranous vesicles. Together with protein 3CD binds the Cis-Active RNA Element (CRE) which is involved in RNA synthesis initiation. Acts as a cofactor to stimulate the activity of 3D polymerase, maybe through a nucleid acid chaperone activity.
Protein 3A:
Localizes the viral replication complex to the surface of membranous vesicles (By similarity).
It inhibits host cell endoplasmic reticulum-to-Golgi apparatus transport and causes the disassembly of the Golgi complex, possibly through GBF1 interaction (By similarity).
This would result in depletion of MHC, trail receptors and IFN receptors at the host cell surface (By similarity).
Plays an essential role in viral RNA replication by recruiting ACBD3 and PI4KB at the viral replication sites, thereby allowing the formation of the rearranged membranous structures where viral replication takes place (Probable).
Viral protein genome-linked:
Acts as a primer for viral RNA replication and remains covalently bound to viral genomic RNA. VPg is uridylylated prior to priming replication into VPg-pUpU (By similarity).
The oriI viral genomic sequence may act as a template for this. The VPg-pUpU is then used as primer on the genomic RNA poly(A) by the RNA-dependent RNA polymerase to replicate the viral genome (By similarity).
Following genome release from the infecting virion in the cytoplasm, the VPg-RNA linkage is probably removed by host TDP2 (By similarity).
During the late stage of the replication cycle, host TDP2 is excluded from sites of viral RNA synthesis and encapsidation, allowing for the generation of progeny virions (By similarity).
Protein 3CD:
Involved in the viral replication complex and viral polypeptide maturation. It exhibits protease activity with a specificity and catalytic efficiency that is different from protease 3C. Protein 3CD lacks polymerase activity. Protein 3CD binds to the 5'UTR of the viral genome.
Protease 3C:
Major viral protease that mediates proteolytic processing of the polyprotein (By similarity).
Cleaves host EIF5B, contributing to host translation shutoff (By similarity).
Cleaves also host PABPC1, contributing to host translation shutoff (By similarity).
Disassembles host cytoplasmic stress granules by cleaving host G3BP1, although this effect is less prononced than the inhibition induced by protease 2A (PubMed:30006004, PubMed:30867299).
Cleaves host DDX58/RIG-I and thus contributes to the inhibition of type I interferon production (PubMed:24390337).
Cleaves host IRF7 and thus contributes to the inhibition of type I interferon production (PubMed:23175366).
Cleaves host HNRNPA1 thereby increasing the translation of apoptosis protease activating factor APAF1, leading to apoptosis of the host cell (PubMed:31498791).
Cleaves host NLRP1, triggers host N-glycine-mediated degradation of the autoinhibitory NLRP1 N-terminal fragment (By similarity).
RNA-directed RNA polymerase:
Replicates the viral genomic RNA on the surface of intracellular membranes. May form linear arrays of subunits that propagate along a strong head-to-tail interaction called interface-I. Covalently attaches UMP to a tyrosine of VPg, which is used to prime RNA synthesis. The positive stranded RNA genome is first replicated at virus induced membranous vesicles, creating a dsRNA genomic replication form. This dsRNA is then used as template to synthesize positive stranded RNA genomes. ss+RNA genomes are either translated, replicated or encapsidated.
Biological Process
Clathrin-dependent endocytosis of virus by host cell Source: UniProtKB-KW
DNA replication Source: UniProtKB-KW
Induction by virus of host autophagy Source: UniProtKB
Modulation by virus of host apoptotic process Source: UniProtKB-KW
Negative regulation of stress granule assembly Source: UniProtKB
Pore formation by virus in membrane of host cell Source: UniProtKB-KW
Pore-mediated entry of viral genome into host cell Source: UniProtKB-KW
Positive stranded viral RNA replication Source: UniProtKB
Protein complex oligomerization Source: UniProtKB-KW
RNA-protein covalent cross-linking Source: UniProtKB-KW
Suppression by virus of host gene expression Source: UniProtKB-KW
Suppression by virus of host MAVS activity Source: UniProtKB-KW
Suppression by virus of host MDA-5 activity Source: UniProtKB-KW
Suppression by virus of host mRNA export from nucleus Source: UniProtKB
Suppression by virus of host RIG-I activity Source: UniProtKB-KW
Suppression by virus of host translation initiation factor activity Source: UniProtKB
Transcription, DNA-templated Source: InterPro
Viral RNA genome replication Source: InterPro
Virion attachment to host cell Source: UniProtKB-KW
Cellular Location
Capsid protein VP0&VP1&VP2&VP3&Viral protein genome-linked: Virion; Host cytoplasm
Capsid protein VP4: Virion
Protein 2B&2C&3A&3AB&RNA-directed RNA polymerase: Host cytoplasmic vesicle membrane. Probably localizes to the surface of intracellular membrane vesicles that are induced after virus infection as the site for viral RNA replication. These vesicles are derived from the endoplasmic reticulum.
Protease 3C: Host cytoplasm
Protein 3CD: Host nucleus; Host cytoplasm; Host cytoplasmic vesicle membrane. Probably localizes to the surface of intracellular membrane vesicles that are induced after virus infection as the site for viral RNA replication. These vesicles are derived from the endoplasmic reticulum.
PTM
Genome polyprotein:
Specific enzymatic cleavages in vivo by the viral proteases yield processing intermediates and the mature proteins.
Capsid protein VP0:
Myristoylation is required for the formation of pentamers during virus assembly. Further assembly of 12 pentamers and a molecule of genomic RNA generates the provirion.By similarity
Capsid protein VP0:
During virion maturation, immature virions are rendered infectious following cleavage of VP0 into VP4 and VP2. This maturation seems to be an autocatalytic event triggered by the presence of RNA in the capsid and it is followed by a conformational change infectious virion.By similarity
Capsid protein VP4:
Myristoylation is required during RNA encapsidation and formation of the mature virus particle.By similarity
Viral protein genome-linked:
VPg is uridylylated by the polymerase into VPg-pUpU. This acts as a nucleotide-peptide primer for the genomic RNA replication.By similarity
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Datasheet