title: ICAM-5/Telencephalin Is a Functional Entry Receptor for Enterovirus D68.
abstract: 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.
authors.affiliation: First Hospital of Jilin University, Institute of Virology and AIDS Research, Changchun, Jilin Province 130021, China. Electronic address: wwei6@jlu.edu.cn.
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
authors.affiliation: First Hospital of Jilin University, Institute of Virology and AIDS Research, Changchun, Jilin Province 130021, China.
authors.forename: Haoran
authors.initials: H
authors.lastname: Guo
authors.affiliation: First Hospital of Jilin University, Institute of Virology and AIDS Research, Changchun, Jilin Province 130021, China.
authors.forename: Junliang
authors.initials: J
authors.lastname: Chang
authors.affiliation: Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, Ministry of Education), Second Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang 310058, China.
authors.forename: Yingzi
authors.initials: Y
authors.lastname: Yu
authors.affiliation: First Hospital of Jilin University, Institute of Virology and AIDS Research, Changchun, Jilin Province 130021, China.
authors.forename: Guanchen
authors.initials: G
authors.lastname: Liu
authors.affiliation: First Hospital of Jilin University, Institute of Virology and AIDS Research, Changchun, Jilin Province 130021, China.
authors.forename: Nannan
authors.initials: N
authors.lastname: Zhang
authors.affiliation: Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe Street, Baltimore, MD 21205, USA; Cellphire, Inc., 9430 Key West Avenue, Rockville, MD 20850, USA.
authors.forename: Stephen H
authors.initials: SH
authors.lastname: Willard
authors.affiliation: Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, Ministry of Education), Second Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang 310058, China.
authors.forename: Shu
authors.initials: S
authors.lastname: Zheng
authors.affiliation: 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: xyu2@jhu.edu.
authors.forename: Xiao-Fang
authors.initials: XF
authors.lastname: Yu
mesh_terms: D015815:Cell Adhesion Molecules / Q000378:metabolism*; D030016:Enterovirus D, Human / Q000502:physiology*; D006801:Humans; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D011485:Protein Binding; D011991:Receptors, Virus / Q000378:metabolism*; D012794:Sialic Acids / Q000378:metabolism; D053585:Virus Attachment; D053586:Virus Internalization
chemical_list: D015815:Cell Adhesion Molecules; C086747:ICAM5 protein, human; D009419:Nerve Tissue Proteins; D011991:Receptors, Virus; D012794:Sialic Acids
keywords: EV-D68; ICAM-5/telencephalin; acute flaccid myelitis; enterovirus; entry receptor; picornaviridae; respiratory illness