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Title: Sialic acid-dependent cell entry of human enterovirus D68

Human enterovirus D68 (EV-D68) is a causative agent of childhood respiratory diseases and has now emerged as a global public health threat. Nevertheless, knowledge of the tissue tropism and pathogenesis of EV-D68 has been hindered by a lack of studies on the receptor-mediated EV-D68 entry into host cells. Here we demonstrate that cell surface sialic acid is essential for EV-D68 to bind to and infect susceptible cells. Crystal structures of EV-D68 in complex with sialylated glycan receptor analogues show that they bind into the ‘canyon’ on the virus surface. The sialic acid receptor induces a cascade of conformational changes in the virus to eject a fatty-acid-like molecule that regulates the stability of the virus. Furthermore, virus binding to a sialic acid receptor and to immunoglobulin-like receptors used by most other enteroviruses share a conserved mechanism for priming viral uncoating and facilitating cell entry.
Authors:
 [1] ;  [1] ;  [2] ;  [1] ;  [3] ;  [2] ;  [2] ;  [1]
  1. Purdue Univ., West Lafayette, IN (United States)
  2. Utrecht Univ., Utrecht (The Netherlands)
  3. Univ. of Texas at El Paso, El Paso, TX (United States)
Publication Date:
Grant/Contract Number:
AC02-06CH11357
Type:
Accepted Manuscript
Journal Name:
Nature Communications
Additional Journal Information:
Journal Volume: 6; Journal ID: ISSN 2041-1723
Publisher:
Nature Publishing Group
Research Org:
Purdue Univ., West Lafayette, IN (United States)
Sponsoring Org:
USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22)
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; biological sciences; virology
OSTI Identifier:
1239678

Liu, Yue, Sheng, Ju, Baggen, Jim, Meng, Geng, Xiao, Chuan, Thibaut, Hendrik J., van Kuppeveld, Frank J. M., and Rossmann, Michael G.. Sialic acid-dependent cell entry of human enterovirus D68. United States: N. p., Web. doi:10.1038/ncomms9865.
Liu, Yue, Sheng, Ju, Baggen, Jim, Meng, Geng, Xiao, Chuan, Thibaut, Hendrik J., van Kuppeveld, Frank J. M., & Rossmann, Michael G.. Sialic acid-dependent cell entry of human enterovirus D68. United States. doi:10.1038/ncomms9865.
Liu, Yue, Sheng, Ju, Baggen, Jim, Meng, Geng, Xiao, Chuan, Thibaut, Hendrik J., van Kuppeveld, Frank J. M., and Rossmann, Michael G.. 2015. "Sialic acid-dependent cell entry of human enterovirus D68". United States. doi:10.1038/ncomms9865. https://www.osti.gov/servlets/purl/1239678.
@article{osti_1239678,
title = {Sialic acid-dependent cell entry of human enterovirus D68},
author = {Liu, Yue and Sheng, Ju and Baggen, Jim and Meng, Geng and Xiao, Chuan and Thibaut, Hendrik J. and van Kuppeveld, Frank J. M. and Rossmann, Michael G.},
abstractNote = {Human enterovirus D68 (EV-D68) is a causative agent of childhood respiratory diseases and has now emerged as a global public health threat. Nevertheless, knowledge of the tissue tropism and pathogenesis of EV-D68 has been hindered by a lack of studies on the receptor-mediated EV-D68 entry into host cells. Here we demonstrate that cell surface sialic acid is essential for EV-D68 to bind to and infect susceptible cells. Crystal structures of EV-D68 in complex with sialylated glycan receptor analogues show that they bind into the ‘canyon’ on the virus surface. The sialic acid receptor induces a cascade of conformational changes in the virus to eject a fatty-acid-like molecule that regulates the stability of the virus. Furthermore, virus binding to a sialic acid receptor and to immunoglobulin-like receptors used by most other enteroviruses share a conserved mechanism for priming viral uncoating and facilitating cell entry.},
doi = {10.1038/ncomms9865},
journal = {Nature Communications},
number = ,
volume = 6,
place = {United States},
year = {2015},
month = {11}
}