Abstract
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.
