Sialic acid-dependent cell entry of human enterovirus D68

作者：Yue Liu, Ju Sheng, Jim Baggen, Geng Meng, Chuan Xiao, Hendrik Jan Thibaut, Frank J. M. van Kuppeveld, Michael G. Rossmann · 发表于：Nature Communications · 年份：2015 · DOI：10.1038/ncomms9865 · 被引用次数：155 · 研究领域：Viral Infections and Immunology Research、Viral gastroenteritis research and epidemiology、Cytomegalovirus and herpesvirus research

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. Thus, 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.