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Scavenger receptor B2 is a cellular receptor for enterovirus 71

Nature Medicine volume 15, pages 798–801 (2009)Cite this article

Abstract

Enterovirus 71 (EV71) belongs to human enterovirus species A of the genus Enterovirus within the family Picornaviridae1. EV71, together with coxsackievirus A16 (CVA16), are most frequently associated with hand, foot and mouth disease (HFMD)1. 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 paralysis2. In recent years, epidemic and sporadic outbreaks of neurovirulent EV71 infections have been reported in Taiwan, Malaysia, Singapore, Japan and China3,4,5,6,7. 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.

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Figure 1: Susceptibility of Ltr051 and Ltr246 cells to EV71.
Figure 2: SCARB2 confers susceptibility to EV71 to mouse L929 cells.
Figure 3: Interaction of SCARB2 with EV71.

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Acknowledgements

We thank H. Shimizu (Japan National Institute of Infectious Diseases) for providing us with all viruses used in this report and critical reading of this manuscript, Y. Kawaoka (University of Tokyo) for providing us with pCAGGS-PUR, Y. Yanagi for critical reading of this manuscript and Y. Matsumoto and K. Kohyama for supporting flow cytometry. This work was supported in part by a grant-in-aid for Scientific Research (C) (20590243) from the Japan Society for the Promotion of Science and in part by a grant-in-aid for Research on Emerging and Re-emerging Infectious Diseases from the Ministry of Health, Labour and Welfare, Japan.

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Author notes

  1. Seiya Yamayoshi, Jifen Li & Satoshi Koike

    Present address: Present addresses: Neurovirology Project, Tokyo Metropolitan Institute of Medical Science, Tokyo Metropolitan Organization for Medical Research, Tokyo, Japan (S.Y. and S.K.) and Center for Translational Medicine, Department of Medicine, Jefferson Medical College, Philadelphia, Pennsylvania, USA (J.L.).,

Authors and Affiliations

  1. Department of Microbiology and Immunology, Tokyo Metropolitan Institute for Neuroscience, Tokyo Metropolitan Organization for Medical Research, Tokyo, Japan

    Seiya Yamayoshi, Yasuko Yamashita, Jifen Li & Satoshi Koike

  2. Japan Health Sciences Foundation, Tokyo, Japan

    Seiya Yamayoshi

  3. Nanotechnology Innovation Center, National Institute for Materials Science, Ibaraki, Japan

    Nobutaka Hanagata, Takashi Minowa & Taro Takemura

  4. Biomaterials Center, National Institute for Materials Science, Ibaraki, Japan

    Nobutaka Hanagata

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Contributions

S.Y. designed and performed the majority of the experiments, analyzed the data and wrote the manuscript; Y.Y. constructed pSVA-EV71-GFP and established Ltr051 and Ltr246 cells; J.L. constructed pSVA-EV71; N.H., T.M. and T.T. performed microarray analysis; S.K. designed the project, assisted with the experiments, analyzed the data and wrote the manuscript.

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Correspondence to Satoshi Koike.

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Supplementary Figs. 1–7, Supplementary Tables 1–3 and Supplementary Methods (PDF 1527 kb)

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Yamayoshi, S., Yamashita, Y., Li, J. et al. Scavenger receptor B2 is a cellular receptor for enterovirus 71. Nat Med 15, 798–801 (2009). https://doi.org/10.1038/nm.1992

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