RRC ID 37611
Author Nishimura Y, Shimojima M, Tano Y, Miyamura T, Wakita T, Shimizu H.
Title Human P-selectin glycoprotein ligand-1 is a functional receptor for enterovirus 71.
Journal Nat Med
Abstract Enterovirus 71 (EV71) is a major causative agent of hand, foot and mouth disease (HFMD), a common febrile disease occurring mainly in young children. Although clinical manifestations of HFMD are usually mild and self limiting, a severe EV71 outbreak can lead to a diverse array of neurological diseases. Identification of the specific cellular receptors is crucial for elucidating the mechanism of early virus-host interactions and the pathogenesis of enteroviruses. Here we identify human P-selectin glycoprotein ligand-1 (PSGL-1; CD162), a sialomucin membrane protein expressed on leukocytes that has a major role in early stages of inflammation, as a functional receptor for EV71 using an expression cloning method by panning. The N-terminal region of PSGL-1 binds specifically to EV71. Stable PSGL-1 expression allowed EV71 entry and replication, and development of cytopathic effects in nonsusceptible mouse L929 cells. Five out of eight EV71 strains bound soluble PSGL-1 and used intact PSGL-1 as the primary receptor for infection of Jurkat T cells. Three other EV71 strains did not use PSGL-1, suggesting the presence of strain-specific replication of EV71 in leukocytes. EV71 replicated in nonleukocyte cell lines in a PSGL-1-independent manner, indicating the presence of alternative receptor(s) for EV71. The identification of PSGL-1 as a receptor for EV71 sheds new light on a role for PSGL-1-positive leukocytes in cell tropism and pathogenesis during the course of HFMD and other EV71-mediated diseases.
Volume 15(7)
Pages 794-7
Published 2009-7-1
DOI 10.1038/nm.1961
PII nm.1961
PMID 19543284
MeSH Animals Cell Line Enterovirus A, Human / pathogenicity* Enterovirus A, Human / physiology Humans Jurkat Cells Membrane Glycoproteins / analysis Membrane Glycoproteins / physiology* Mice Receptors, Virus / analysis Receptors, Virus / physiology* Virus Replication
IF 36.13
Times Cited 258
WOS Category MEDICINE, RESEARCH & EXPERIMENTAL BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY
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The most frequently cited source Patent(IFI CLAIMS)
Total number of mentions 10
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Resource
Human and Animal Cells Jurkat(RCB0806)