Human P-selectin glycoprotein ligand-1 is a functional receptor for enterovirus 71.
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.
Nishimura
Yorihiro
Y
Department of Virology II, National Institute of Infectious Diseases, Musashimurayama-shi, Tokyo, Japan.
Shimojima
Masayuki
M
Tano
Yoshio
Y
Miyamura
Tatsuo
T
Wakita
Takaji
T
Shimizu
Hiroyuki
H
D000818:Animals; D002460:Cell Line; D029821:Enterovirus A, Human / Q000472:pathogenicity* / Q000502:physiology; D006801:Humans; D019169:Jurkat Cells; D008562:Membrane Glycoproteins / Q000032:analysis / Q000502:physiology*; D051379:Mice; D011991:Receptors, Virus / Q000032:analysis / Q000502:physiology*; D014779:Virus Replication
D008562:Membrane Glycoproteins; C084882:P-selectin ligand protein; D011991:Receptors, Virus