ICAM-5/Telencephalin Is a Functional Entry Receptor for Enterovirus D68.

Cell Host Microbe

First Hospital of Jilin University, Institute of Virology and AIDS Research, Changchun, Jilin Province 130021, China; Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, Ministry of Education), Second Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang 310058, China; Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe Street, Baltimore, MD 21205, USA. Electronic address:

Published: November 2016

Enterovirus D68 (EV-D68) is a member of the Picornaviridae family. Although EV-D68-associated infection was once considered rare, it has been increasing in recent years. EV-D68 infection is most frequently associated with respiratory illness. However, it has also been implicated in a polio-like neurological disorder, acute flaccid myelitis. Although sialic acid has been implicated in EV-D68 entry, the existence of a protein receptor has yet to be clarified. Here we identify neuron-specific intercellular adhesion molecule 5 (ICAM-5/telencephalin) as a cellular receptor for sialic acid-dependent and -independent EV-D68 viruses. EV-D68 bound specifically and efficiently to ICAM-5, and replication of EV-D68 in diverse cell types was inhibited by soluble ICAM-5 fragments. ICAM-5 silencing attenuated EV-D68 replication in permissive cells, and ICAM-5 expression in non-permissive cells allowed EV-D68 replication. The discovery of a neuron-specific adhesion molecule as an EV-D68 receptor has important implications for EV-D68 pathogenesis and may facilitate the development of novel intervention strategies.

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http://dx.doi.org/10.1016/j.chom.2016.09.013DOI Listing

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