Scavenger receptor B2 is a cellular receptor for enterovirus 71

Abstract

Enterovirus 71 (EV71) belongs to human enterovirus species A of the genus Enterovirus within the family Picornaviridae. EV71, together with coxsackievirus A16 (CVA16), are most frequently associated with hand, foot and mouth disease (HFMD). Although HFMD is considered a mild exanthematous infection, infections involving EV71, but not CVA16, can progress to severe neurological disease, including fatal encephalitis, aseptic meningitis and acute flaccid paralysis. In recent years, epidemic and sporadic outbreaks of neurovirulent EV71 infections have been reported in Taiwan, Malaysia, Singapore, Japan and China. Here, we show that human scavenger receptor class B, member 2 (SCARB2, also known as lysosomal integral membrane protein II or CD36b like-2) is a receptor for EV71. EV71 binds soluble SCARB2 or cells expressing SCARB2, and the binding is inhibited by an antibody to SCARB2. Expression of human SCARB2 enables normally unsusceptible cell lines to support EV71 propagation and develop cytopathic effects. EV71 infection is hampered by the antibody to SCARB2 and soluble SCARB2. SCARB2 also supports the infection of the milder pathogen CVA16. The identification of SCARB2 as an EV71 and CVA16 receptor contributes to a better understanding of the pathogenicity of these viruses.

Initial evidence on differences among Enterovirus 71, Coxsackievirus A16 and Coxsackievirus B4 in binding to cell surface heparan sulphate

“…One explanation might be that this highly passaged cloned strain of EV71 might have lost its ability to interact with HS through consecutive passages. It can also be suggested that this strain of EV71 may largely utilize one of the two recently suggested candidates for cell receptors of EV71 for fibroblasts and epithelial cell lines; SCARB2 [22], or sialic acid-linked glycans [23], independent of cell surface HS. Therefore, whilst the role of HS in interacting with this cloned strain of EV71 may not be completely overlooked, the virus adsorption is not essentially and selectively dependent on cell surface HS in Vero cells.…”

“…It is noteworthy that although Human Scavenger Receptor Class B, Member 2 (SCARB2) was previously demonstrated to be the dominant EV71 receptor in epithelial cell lines [22], the presence of another minor receptor(s) in one of the tested susceptible cell lines was also suggested, which could facilitate EV71 infection through a SCARB2-independent pathway [22]. This is also in agreement with a general fact that picornaviruses easily adapt to bind to different co-receptor(s) even in the same cell type due to having the flexibility in receptor usage [1,6,24].…”

“…Therefore, it cannot be confirmed that cell surface HS serves as a selective and necessary attachment co-receptor for CVA16 adsorption. It has recently been discovered that SCARB2 can serve as an attachment receptor for CVA16 in epithelial cell lines [22]. Thus, one could propose that the clinical CVA16 might use SCARB2 or another yet to be identified cell receptor to bind to Vero cells, independent of HS.…”

Hand, Foot and Mouth Disease: A case report

“…The remaining skin part; particularly buttock, perianal and other region were free of any lesion. (PSGL-1), human scavenger receptor class B, member 2 (SCARB2), and sialic-acid-linked glycanact as functional receptors for EV71 by using different human cell lines and different cloning strategies [6,7,8].…”

Antiviral activity of acid beta-glucosidase 1 on enterovirus 71, a causative agent of hand, foot and mouth disease

“…In 2009, researchers reported the discovery of two EV71 receptors, i.e. human scavenger receptor class B, member 2 (SCARB2), also known as lysosomal integral membrane protein 2 (LIMP-2) or CD36b like-2; and P-selectin glycoprotein ligand-1 (PSGL-1), also known as CD162 [9][10][11]. SCARB2 is expressed in most cell types, whereas PSGL-1 is limited to blood cells and endothelial cells, suggesting a distinct role for these two receptors in the pathogenesis of EV71 infection in vivo [12].…”