Abstract
BackgroundThe incidence of neurological complications and fatalities associated with Hand, Foot & Mouth disease has increased over recent years, due to emergence of newly-evolved strains of Enterovirus 71 (EV71). In the search for new antiviral therapeutics against EV71, accurate and sensitive in vitro cellular models for preliminary studies of EV71 pathogenesis is an essential prerequisite, before progressing to expensive and time-consuming live animal studies and clinical trials.MethodsThis study thus investigated whether neural lineages derived from pluripotent human embryonic stem cells (hESC) can fulfil this purpose. EV71 infection of hESC-derived neural stem cells (NSC) and mature neurons (MN) was carried out in vitro, in comparison with RD and SH-SY5Y cell lines.ResultsUpon assessment of post-infection survivability and EV71 production by the various types, it was observed that NSC were significantly more susceptible to EV71 infection compared to MN, RD (rhabdomyosarcoma) and SH-SY5Y cells, which was consistent with previous studies on mice. The SP81 peptide had significantly greater inhibitory effect on EV71 production by NSC and MN compared to the cancer-derived RD and SH-SY5Y cell lines.ConclusionsHence, this study demonstrates that hESC-derived neural lineages can be utilized as in vitro models for studying EV71 pathogenesis and for screening of antiviral therapeutics.
Highlights
The incidence of neurological complications and fatalities associated with Hand, Foot & Mouth disease has increased over recent years, due to emergence of newly-evolved strains of Enterovirus 71 (EV71)
In the research and development pipeline, accurate and sensitive in vitro cellular models for investigating EV71 pathogenesis are of paramount importance in the preliminary screening and testing of newly-developed antiviral agents, before progressing to expensive and time-consuming in vivo animal studies, followed by clinical trials in human patients
The objective of this study is to investigate EV71 infection of human embryonic stem cells (hESC)-derived mature neurons and neural stem cells in vitro, in comparison with RD cells that is commonlyutilized for EV71 studies [5], as well as with a neuroblastoma-derived cell line SH-SY5Y [25]
Summary
The incidence of neurological complications and fatalities associated with Hand, Foot & Mouth disease has increased over recent years, due to emergence of newly-evolved strains of Enterovirus 71 (EV71). In the search for new antiviral therapeutics against EV71, accurate and sensitive in vitro cellular models for preliminary studies of EV71 pathogenesis is an essential prerequisite, before progressing to expensive and time-consuming live animal studies and clinical trials. In the research and development pipeline, accurate and sensitive in vitro cellular models for investigating EV71 pathogenesis are of paramount importance in the preliminary screening and testing of newly-developed antiviral agents, before progressing to expensive and time-consuming in vivo animal studies, followed by clinical trials in human patients. There are inherent genetic abnormalities and karyotypic instability
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