Receptors for enterovirus 71

Yamayoshi, Seiya; Fujii, Ken; Koike, Sachiko

doi:10.1038/emi.2014.49

Cited by 70 publications

(59 citation statements)

References 71 publications

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“…Recently, several molecules that act as cell surface receptors for EV71 have been identified, such as scavenger receptor B2 (SCARB2), P-selection glycoprotein ligand 1 (PSGL-1), annexin II (Anx2), sialylated glycan, and heparan sulfate353649). SCARB2 plays major roles in attachment, viral entry, and uncoating, and it can enable effective EV71 infection35).…”

Section: Pathophysiology Of Pulmonary Hemorrhage/edema In Ev71 Brainsmentioning

confidence: 99%

“…In addition, SCARB2 plays key roles in the development of EV71 neurological disease in vivo . PSGL-1, Anx2, sialylated glycan, and heparan sulfate are attachment receptors, which potentiate viral infection3649). However, despite the discovery of these receptors, the reason for EV71 neurotropism on the brainstem is still unknown.…”

Section: Pathophysiology Of Pulmonary Hemorrhage/edema In Ev71 Brainsmentioning

confidence: 99%

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Enterovirus 71 infection and neurological complications

Lee

2016

Korean J Pediatr

122

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Since the outbreak of the enterovirus 71 (EV71) infection in Malaysia in 1997, large epidemics of EV71 have occurred in the Asia-Pacific region. Many children and infants have died from serious neurological complications during these epidemics, and EV71 infection has become a serious public health problem in these areas. EV71 infection causes hand, foot and mouth disease (HFMD) in children, and usually resolves spontaneously. However, EV71 occasionally involves the central nervous system (CNS), and induces diverse neurological complications such as brainstem encephalitis, aseptic meningitis, and acute flaccid paralysis. Among those complications, brainstem encephalitis is the most critical neurological manifestation because it can cause neurogenic pulmonary hemorrhage/edema leading to death. The characteristic clinical symptoms such as myoclonus and ataxia, cerebrospinal fluid (CSF) pleocytosis, and brainstem lesions on magnetic resonance imaging, in conjunction with the skin rash of HFMD and the isolation of EV71 from a stool, throat-swab, or CSF sample are typical findings indicating CNS involvement of EV71 infection. Treatment with intravenous immunoglobulin and milrinone are recommended in cases with severe neurological complications from EV71 infection, such as brainstem encephalitis. Despite the recent discovery of receptors for EV71 in human cells, such as the scavenger receptor B2 and P-selection glycoprotein ligand 1, it is not known why EV71 infection predominantly involves the brainstem. Recently, 3 companies in China have completed phase III clinical trials of EV71 vaccines. However, the promotion and approval of these vaccines in various countries are problems yet to be resolved.

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Section: Pathophysiology Of Pulmonary Hemorrhage/edema In Ev71 Brainsmentioning

confidence: 99%

Section: Pathophysiology Of Pulmonary Hemorrhage/edema In Ev71 Brainsmentioning

confidence: 99%

Enterovirus 71 infection and neurological complications

Lee

2016

Korean J Pediatr

122

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“…All keratinocytes were also SCARB2-positive (Fig. 3O) confirming the ubiquitous distribution of SCARB2 in most cells and tissues181920. Other HFMD-causing, SCARB2-associated enteroviruses such as coxsackievirus A7 (CVA-7), CVA-14 and CVA-1621 may likewise infect squamous cells but so far there is no evidence for this.…”

Section: Discussionmentioning

confidence: 71%

Squamous epitheliotropism of Enterovirus A71 in human epidermis and oral mucosa

Phyu

Ong

Kong

et al. 2017

Sci Rep

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Hand-foot-and-mouth disease is a self-limiting paediatric infectious disease commonly caused by Enterovirus A71 (Genus: Enterovirus, Family: Picornaviridae). Typical lesions in and around the hands, feet, oral cavity and other places may rarely be complicated by acute flaccid paralysis and acute encephalomyelitis. Although virus is readily cultured from skin vesicles and oral secretions, the cellular target/s of Enterovirus A71 in human skin and oral mucosa are unknown. In Enterovirus A71-infected human skin and oral mucosa organotypic cultures derived from the prepuce and lip biopsies, focal viral antigens and viral RNA were localized to cytoplasm of epidermal and mucosal squamous cells as early as 2 days post-infection. Viral antigens/RNA were associated with cytoplasmic vacuolation and cellular necrosis. Infected primary prepuce epidermal keratinocyte cultures showed cytopathic effects with concomitant detection of viral antigens from 2 days post-infection. Supernatant and/or tissue homogenates from prepuce skin organotypic cultures and primary prepuce keratinocyte cultures showed viral titres consistent with active viral replication. Our data strongly support Enterovirus A71 squamous epitheliotropism in the human epidermis and oral mucosa, and suggest that these organs are important primary and/or secondary viral replication sites that contribute significantly to oral and cutaneous viral shedding resulting in person-to-person transmission, and viraemia, which could lead to neuroinvasion.

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“…Hence, we believe our MAb interferes with EV-A71 binding to hSCARB2 receptor. The low neutralizing titers observed in RD cells could be related to the existence of several alternative viral-binding receptors such as Pselectin glycoprotein ligand-1, sialylated glycan, nucleolin, heparan sulfate, annexin II or other unindentified receptor(s) as demonstrated previously (Yamayoshi et al, 2014). The hSCARB2 receptor appears to bind to the canyon of the VP1 protein of EV-A71 around the residue Gln-172 (Yamayoshi et al, 2014).…”

Section: Discussionmentioning

confidence: 82%

A monoclonal antibody to ameliorate central nervous system infection and improve survival in a murine model of human Enterovirus-A71 encephalomyelitis

et al. 2016

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Keywords:Enterovirus A71 Monoclonal antibody Therapeutic used Mouse model of human EV-A71 encephalomyelitis a b s t r a c t Background: Enterovirus A71 (EV-A71) encephalomyelitis is an often fatal disease for which there is no specific treatment available. Passive immunization with a specific monoclonal antibody to EV-A71 was used on a murine model of EV-A71 encephalomyelitis to evaluate its therapeutic effectiveness before and after established central nervous system (CNS) infection. Methods: Mice were intraperitoneally-infected with a mouse-adapted EV-A71 strain and treated with a dose of monoclonal antibody (MAb) daily for 3 days on day 1, 2 and 3 post-infection or for 3 days on 3, 4 and 5 post-infection. Treatment effectiveness was evaluated by signs of infection and survival rate. Histopathology and qPCR analyses were performed on mice sacrificed a day after completing treatment. Results: In mock-treated mice, CNS infection was established from day 3 post-infection. All mice treated before established CNS infection, survived and recovered completely without CNS infection. All mice treated after established CNS infection survived with mild paralysis, and viral load and antigens/RNA at day 6 post-infection were significantly reduced. Conclusions: Passive immunization with our MAb could prevent CNS infection in mice if given early before the establishment of CNS infection. It could also ameliorate established CNS infection if optimal and repeated doses were given.

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Receptors for enterovirus 71

Cited by 70 publications

References 71 publications

Enterovirus 71 infection and neurological complications

Enterovirus 71 infection and neurological complications

Squamous epitheliotropism of Enterovirus A71 in human epidermis and oral mucosa

A monoclonal antibody to ameliorate central nervous system infection and improve survival in a murine model of human Enterovirus-A71 encephalomyelitis

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