Scavenger receptor B2 is a cellular receptor for enterovirus 71

Yamayoshi S., et al. Nature Medicine. 15,798 - 801 (2009)

Speaker : Chia-Ming Liu (劉佳明)                                    Time: 15:10~16:00, Sep. 16, 2009

Commentator: Dr. Shun-hua Chen (陳舜華 博士)           Place: Room 601

Abstract:

Enterovirus 71 (EV71) is a small RNA virus that belongs to human enterovirus species A of the genus Enterovirus within Picornaviridae. In 1998, EV71 infected thousands of children in Taiwan, and 320 children were hospitalized with neurologic disease as brainstem encephalitis and polio-like flaccid paralysis¹. EV71 appears to be an increasingly important neurotopic enterovirus, but its receptors facilitating cell entry is unknown. The identification of receptors for EV71 is an important step toward understanding how EV71 causes disease. In this paper, the scavenger receptor class B, member 2 (SCARB2) was identified to be a receptor for EV71. In the transformed mouse fibroblasts with human genomic DNA, two distinct transformants were found to be susceptible to EV71 infection. After human microarray analysis, one of the susceptible transformant was associated with the presence of genomic DNA encoding human SCARB2. SCARB2 is a type Ⅲ double-transmembrane protein and is mainly located in lysosomes and endosomes². In mouse fibroblasts transfected with plasmid encoding SCARB2 (L-SCARB2) cells, SCARB2 can express on the plasma membrane as that of RD cells. The growth kinetic of EV71 and cytopathic effects in L-SCARB2 cell was similar to those in RD cell. SCARB2 can specifically bind EV71 and mediated the attachment of EV71 to the cell. EV71 infection was inhibited by pretreatment with antibody to SCARB2 or the SCARB2-Fc in L-SCARB2 cells and RD cells. In addition CVA 16 was able to infect cell in SCARB2- dependent pathway. The identification of SCARB2 as an EV71 and CVA16 receptor will shed light on our understanding of this disease pathogenesis.

References:

1.    Huang, C.C. et al. Neurologic complications in children with enterovirus 71 infection. The New England Journal of Medicine. 341, 936–942 (1999).

2.    Eskelinen, E.L., et al. At the acidic edge: emerging functions for lysosomal membrane proteins. Trends in Cell Biology. 13, 137–145(2003).