RRC ID |
37611
|
著者 |
Nishimura Y, Shimojima M, Tano Y, Miyamura T, Wakita T, Shimizu H.
|
タイトル |
Human P-selectin glycoprotein ligand-1 is a functional receptor for enterovirus 71.
|
ジャーナル |
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.
|
巻・号 |
15(7)
|
ページ |
794-7
|
公開日 |
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
|
引用数 |
258
|
WOS 分野
|
MEDICINE, RESEARCH & EXPERIMENTAL
BIOCHEMISTRY & MOLECULAR BIOLOGY
CELL BIOLOGY
|
リソース情報 |
ヒト・動物細胞 |
Jurkat(RCB0806) |