Binding to Decay-Accelerating Factor Is Not Required for Infection of Human Leukocyte Cell Lines by Enterovirus 70

Abstract

Enterovirus 70 (EV70) is one of several human enteroviruses that exhibit a propensity for infecting the central nervous system (CNS). The mechanisms by which neurotropic enteroviruses gain access to and invade the CNS are poorly understood. One possibility is that circulating leukocytes become infected and carry neurotropic enteroviruses to the CNS. We examined the ability of EV70 to infect cell lines derived from lymphoid, myeloid, and monocytic lineages. Most leukocyte cell lines tested bound radiolabeled EV70 and were permissive for EV70 replication, suggesting that EV70, in contrast to other enteroviruses, has an in vitro tropism that includes lymphoid, monocytic, and myeloid cell lines. For some of the cell lines, virus binding and infection correlated with surface expression of decay-accelerating factor (DAF), an attachment protein for EV70 on HeLa cells. However, EV70 also adsorbed to and infected cell lines that expressed little or no DAF.In contrast to what was observed for HeLa cells, neither DAF-specific monoclonal antibodies nor phosphatidylinositol-specific phospholipase C treatment inhibited EV70 binding to permissive leukocyte cell lines, and antibody blockade of DAF had little or no effect on EV70 replication. We also found that neither the human coxsackievirus-adenovirus receptor nor intercellular cell adhesion molecule 1, which mediate the entry of coxsackie B viruses and coxsackievirus A21, respectively, functions as a receptor for EV70. EV70 binding to all cell lines was sensitive to sialidase treatment and to inhibition of O glycosylation by benzyl N-acetyl-␣-Dgalactosaminide. Taken together, these results suggest that a sialylated molecule(s) other than DAF serves as a receptor for EV70 on permissive human leukocyte cell lines.

Enterovirus 94, a proposed new serotype in human enterovirus species D

“…The other serotypes of HEV-D (EV68 and EV70) use DAF as a receptor in HeLa cells (Karnauchow et al, 1996;Blomqvist et al, 2002). EV70 also uses sialic acid-containing receptors in a variety of other human cell lines (Alexander & Dimock, 2002;Haddad et al, 2004;Nokhbeh et al, 2005). Our results suggest that EV94 does not need DAF to infect RD cells.…”

Differential permissivity of human cerebrovascular endothelial cells to enterovirus infection and specificities of serotype EV-A71 in crossing an in vitro model of the human blood–brain barrier

“…As this inflammatory disease of the subarachnoid space is common to most EV serotypes, it is assumed that viruses travel through the blood, breaching the blood-CSF barrier either directly or through infected leukocytes. A number of studies showed that PV, CV-B3 and EV-A71 could infect various immune cells (Eberle et al, 1995;Vuorinen et al, 1996;Haddad et al, 2004;Wahid et al, 2005a, b;Tabor-Godwin et al, 2010). These data suggest a role of infected leukocytes in EV dissemination to the CNS through a 'Trojan horse' process.…”

Enterovirus 70 Binds to Different Glycoconjugates Containing α2,3-Linked Sialic Acid on Different Cell Lines

“…Previously, we demonstrated that the glycosyl phosphatidylinositol (GPI)-linked protein CD55 plays a major role in EV70 binding to, and infection of, HeLa cells (35,36). However, EV70 attachment to all other human cell lines that we have tested was CD55 independent but required sialic acid, as determined by sensitivity to Vibrio cholerae sialidase, and sialidase treatment of HeLa cells also reduced EV70 binding (1,28). Like EV70, both adenovirus 37 and some avian influenza A viruses, in particular H7 subtypes, are associated with eye infections (4,5,13,24,39,64).…”