[Source: Cell Host & Microbe, full page: (LINK). Abstract, edited.]
ICAM-5/Telencephalin Is a Functional Entry Receptor for Enterovirus D68
Wei Wei, Haoran Guo, Junliang Chang, Yingzi Yu, Guanchen Liu, Nannan Zhang, Stephen H. Willard, Shu Zheng, Xiao-Fang Yu5
Publication stage: In Press Corrected Proof / DOI: http://dx.doi.org/10.1016/j.chom.2016.09.013
Published: October 27, 2016 – Accepted: September 21, 2016 – Received in revised form: August 5, 2016 – Received: May 13, 2016
- ICAM-5 expression is associated with host cell susceptibility to EV-D68
- EV-D68 viruses bind specifically to ICAM-5
- Soluble ICAM-5 fragments efficiently inhibit EV-D68 infection in vitro and in vivo
- ICAM-5 mediates viral infection of prototype Fermon and circulating EV-D68 strains
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.
Keywords: EV-D68, ICAM-5/telencephalin, entry receptor, acute flaccid myelitis, enterovirus, picornaviridae, respiratory illness
Received: May 13, 2016; Received in revised form: August 5, 2016; Accepted: September 21, 2016; Published: October 27, 2016
© 2016 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
Keywords: EV-D68; Acute Flaccid Myelitis; Picornavirus.