Stem Cell-Derived Neuronal Cells for the Study of Enterovirus Neuropathogenicity

EV71 is a single strand positive RNA virus that has been frequently caused epidemics in Asia-Pacific countries. Serious neurological complications may occur and result in unfavorable outcomes. The fatality of EV71 infection is related to the occurrence of neurological complications. However, the neuropathogenesis of EV71 is unclear. Previous studies about neurotrophic viruses are hampered by difficulty in isolation and expansion of primary neurons. Thus, most neurotrophic virus studies utilized neuroblastoma or glioblastoma cell lines as host cells. However, most cell lines are derived from the cancer tissue, and thus the properties of these cells are different from the normal somatic cells. Recent advances in stem cell biology provide an approach by using the stem cell-differentiated neural cells for studying the neurotrophic virus infection. The obtained differentiated cells behave like the normal cells and possess the specific bioactivities. Therefore, these cells are appropriate to serve as host cells and be applied for virus study. We have applied the stem cell-differentiated neuronal cells to investigate the effects of EV71 infection. Our preliminary results showed that different neuronal cells have varied EV71 susceptibility. In addition, EV71 infection can trigger the enhanced expression of cytokines/chemokine. Furthermore, we can also observe the similar results in animal experiments. Thus, using the differentiated cells as cell model may serve as a better platform for EV71 study. So far, there is no similar results have been reported. To further investigate the related mechanisms may provide evidences about the neuropathogenesis of EV71 infection. In this study, we have four specific aims: (1) To differentiate human stem cells toward various neuronal cells and test their susceptibility to EV71 infection. (2) To examine the EV71 replication in neuronal cells and examine the associated host factors. (3) To elucidate the induced immune responses of susceptible neural cells in response to EV71 infection. (4) To investigate the EV71 infection of neuronal cells in vivo by using human neural stem cell transplanted mouse model.

Project ID:PC10501-1881
External Project ID:MOST104-2320-B182-024-MY3