Investigation of enterovirus 71 cellular receptor interactions

[Truncated abstract] Enterovirus 71 (EV71) is a member of the Human Enterovirus A species of the family Picornaviridae. Since its discovery in 1969, EV71 has caused numerous outbreaks of disease throughout the world. Infections manifest most frequently as hand, foot and mouth disease (HFMD) and in a small proportion of cases, infection can lead to severe neurological disease. Since 1997, there has been a significant increase in EV71 activity in the Asia-Pacific region with a concurrent increase in neurological sequelae. EV71 shares many similarities with poliovirus including disease outcome, pathology and epidemiological behaviour, and with the near-eradication of poliovirus, EV71 has emerged as the leading cause of childhood neurological infection. Currently there are no specific anti-viral drugs or vaccines to control EV71 infection and there is a limited understanding of its pathogenesis. The interaction of a virus with a specific receptor is the first step in a viral infection and is an important determinant of host range, tissue tropism and pathogenesis. The identification and characterisation of EV71 receptors will aid in the development of vaccines and anti-viral therapies. Recently, several receptors for EV71 have been identified, these include: scavenger receptor class B member 2 (SR-B2) (Yamayoshi et al., 2009), P-selectin glycoprotein ligand-1 (PSGL-1) (Nishimura et al., 2009) and in this study, heparan sulphate (HS). The EV71-HS interaction was characterised through a range of binding and infectivity assays using the HS analogue heparin and mutant CHO cell lines deficient in GAG expression, and EV71 entry into RD and CHO cells was found to involve HS. Combined inhibitory treatments to SR-B2, PSGL-1 and HS, indicated that EV71 could use multiple receptors and receptor usage was dependent on virus strain and cell line, highlighting the complexity of the EV71 infection process.