[Identification of P-selectin glycoprotein ligand-1 as one of the cellular receptors for enterovirus 71].
Enterovirus 71 (EV71) is a major causative agent of hand, foot and mouth disease (HFMD), a common febrile disease in young children. Although clinical manifestations of HFMD are usually mild and self-limiting, EV71 can cause large outbreaks of HFMD including severe neurological complications. We identified human P-selectin glycoprotein ligand-1 (PSGL-1; CD162) as a functional receptor for EV71 using an expression cloning method with a human T cell cDNA library by panning. PSGL-1 is a sialomucin membrane protein, expressed on leukocytes, that has a major role in early stages of inflammation by interacting with selections and chemokines. EV71 specifically binds to the N terminal region of PSGL-1 and the expression of human PSGL-1 allowed EV71 replication in nonsusceptible mouse cells, suggesting that PSGL-1 is a functional EV71 receptor. We found the presence of strain-specific EV71 replication in leukocytes. In addition, EV71 replicates in nonleukocyte cell lines in a PSGL-1-independent manner. Thus, further elucidation of the PSGL-1-dependent EV71 replication may provide valuable insights into the molecular basis of EV71 infection including HFMD and various neurological diseases.
Nishimura
Yorihiro
Y
Department of Virology II, National Institute of Infectious Diseases, 4-7-1 Gakuen, Musashimurayama-shi, Tokyo 208-0011, Japan. ynishi@nih.go.jp
Shimizu
Hiroyuki
H
D000818:Animals; D002493:Central Nervous System Diseases / Q000821:virology; D029821:Enterovirus A, Human / Q000472:pathogenicity / Q000502:physiology; D006232:Hand, Foot and Mouth Disease / Q000821:virology; D006801:Humans; D007962:Leukocytes / Q000821:virology; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000302:isolation & purification / Q000502:physiology; D051379:Mice; D011991:Receptors, Virus; D014779:Virus Replication
D008562:Membrane Glycoproteins; C084882:P-selectin ligand protein; D011991:Receptors, Virus