enterovirus 71

Human enterovirus 71 genome polyprotein is a member of the picornaviruses polyprotein family. It contains two peptidase C3 domains, one RdRp catalytic domain, one SF3 helicase domain. Genome polyprotein is cleaved into the following 12 chains: Protein VP (VP4-VP2), Protein VP4 (P1A), Protein VP2 (P1B), Protein VP3 (P1C), Protein VP1 (P1D), Picornain 2A (P2A), Protein 2B (P2B), Protein 2C (P2C), Protein 3A (P3A), Protein 3B (P3B), Picornain 3C (Protease 3C) and RNA-directed RNA polymerase 3D-POL (P3D-POL). VP precursor is a component of immature procapsids. Capsid proteins VP1, VP2, VP3 and VP4 form a closed capsid enclosing the viral positive strand RNA genome. VP4 lies on the inner surface of the protein shell formed by VP1, VP2 and VP3. All the three latter proteins contain a beta-sheet structure called beta-barrel jelly roll. Together they form an icosahedral capsid composed of 6 copies of each VP1, VP2, and VP3, with a diameter of approximately 3 Angstroms. VP1 is situated at the 12 fivefold axes, whereas VP2 and VP3 are located at the quasi-sixfold axes.

Scavenger Receptor Class B Member 2 (SCARB2) is a type III multi-pass membrane glycoprotein that is located primarily in limiting membranes of lysosomes and endosomes on all tissues and cell types so far examined. Earlier studies in mice and rat suggested that this protein may participate in membrane transportation and the reorganization of endosomal/lysosomal compartment. The protein deficiency in mice was reported to impair cell membrane transport processes and cause pelvic junction obstruction, deafness, and peripheral neuropathy. Further studies in human showed that this protein is identified as a receptor for EV71 (human enterovirus species A, Enterovirus 71) and CVA16 (coxsackievirus A16) which are most frequently associated with hand, foot and mouth disease (HFMD). Mutations in this gene caused an autosomal recessive progressive myoclonic epilepsy-4 (EPM4), also known as action myoclonus-renal failure syndrome (AMRF). Alternatively spliced transcript variants encoding different isoforms have been found for this gene. In addition, SCARB2 also has been shown to bind thrombospondin-1, may contribute to the pro-adhesive changes of activated platelets during coagulation, and inflammation.

Protein with pleiotropic attributes mediated in a cell-compartment- and tissue-specific manner, which include the plasma membrane-associated cell signaling functions, mitochondrial chaperone, and transcriptional co-regulator of transcription factors in the nucleus. Plays a role in adipose tissue and glucose Homeostasis in a sex-specific manner. Contributes to pulmonary vascular remodeling by accelerating proliferation of pulmonary arterial smooth muscle cells.; In the mitochondria, together with PHB2, forms large ring complexes (prohibitin complexes) in the inner mitochondrial membrane (IMM) and functions as chaperone protein that stabilizes mitochondrial respiratory enzymes and maintains mitochondrial integrity in the IMM, which is required for mitochondrial morphogenesis, neuronal survival, and normal lifespan (Probable). The prohibitin complex, with DNAJC19, regulates cardiolipin remodeling and the protein turnover of OMA1 in a cardiolipin-binding manner. Regulates mitochondrial respiration activity playing a role in cellular aging. The prohibitin complex plays a role of mitophagy receptor involved in targeting mitochondria for autophagic degradation. Involved in mitochondrial-mediated antiviral innate immunity, activates DDX58/RIG-I-mediated signal transduction and production of IFNB1 and proinflammatory cytokine IL6.; In the nucleus, acts as a transcription coregulator, enhances promoter binding by TP53, a transcription factor it activates, but reduces the promoter binding by E2F1, a transcription factor it represses. Interacts with STAT3 to affect IL17 secretion in T-helper Th17 cells.; In the plasma membrane, cooperates with CD86 to mediate CD86-signaling in B lymphocytes that regulates the level of IgG1 produced through the activation of distal signaling intermediates. Upon CD40 engagement, required to activate NF-kappa-B signaling pathway via phospholipase C and protein kinase C activation.; (Microbial infection) In neuronal cells, cell surface-expressed PHB is involved in human enterovirus 71/EV-71 entry into neuronal cells specifically, while membrane-bound mitochondrial PHB associates with the virus replication complex and facilitates viral replication. May serve as a receptor for EV71.

Lysosome membrane protein II (LIMPII)，also known as SCARB2, is a type III multi-pass membrane glycoprotein that is located primarily in limiting membranes of lysosomes and endosomes on all tissues and cell types so far examined. Earlier studies in mice and rat suggested that this protein may participate in membrane transportation and the reorganization of endosomal/lysosomal compartment. The protein deficiency in mice was reported to impair cell membrane transport processes and cause pelvic junction obstruction, deafness, and peripheral neuropathy. Further studies in human showed that this protein is identified as a receptor for EV71 (human enterovirus species A, Enterovirus 71) and CVA16 (coxsackievirus A16) which are most frequently associated with hand, foot and mouth disease (HFMD). Mutations in this gene caused an autosomal recessive progressive myoclonic epilepsy-4 (EPM4), also known as action myoclonus-renal failure syndrome (AMRF). Alternatively spliced transcript variants encoding different isoforms have been found for this gene. In addition, LIMPII also has been shown to bind thrombospondin-1, may contribute to the pro-adhesive changes of activated platelets during coagulation, and inflammation.