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Zika Virus Infection of Cultured Human Fetal Brain Neural Stem Cells for Immunocytochemical Analysis
Published on: February 5, 2018
Cellular responses to Sindbis virus infection of neural progenitors derived from human embryonic stem cells
Jie Xu, Rodney J Nash, Teryl K Frey1
1Department of Biology, Georgia State University, Atlanta, GA, USA. tfrey@gsu.edu.
Background:
Sindbis virus (SINV) causes age-dependent encephalitis in mice, and therefore serves as a model to study viral encephalitis. SINV is used as a vector for the delivery of genes into selected neural stem cell lines; however, the toxicity and side effects of this vector have rarely been discussed. In this context, we investigated the cellular responses of human embryonic stem cell (hESCs) derived neural progenitors (hNPCs) to SINV infection by assessing susceptibility of the cells to SINV infection, analyzing the effect of infection on cell proliferation and cell death, and examining the impact of SINV infection on hNPCs markers of stemness.
Findings:
We found that hNPCs are highly susceptible to SINV infection. Upon infection, the viruses induced apoptosis to hNPCs while not affecting the expression of cell proliferation markers. Lastly, SINV infections result in significant changes in the expression of key regulators of hNPCs' plasticity and homeostasis.
Conclusion:
The robust and versatile signaling, proliferation, and other cell responses of hESCs-derived hNPCs to virus infection demonstrated that it is a good model to study the pathogenesis of viral-induced neurodevelopmental and degenerative diseases. On the other hand, the toxicity of SINV to hNPCs cells cannot be ignored, and therefore extra care should be taken when using SINV as a vector to deliver genes into human stem cell lines.
Insights
Sindbis virus (SINV) infects human neural progenitor cells (hNPCs), causing cell death but not affecting proliferation. SINV toxicity to hNPCs warrants caution when using it as a gene delivery vector.
Area of Science:
- Neuroscience
- Stem Cell Biology
- Virology
Background:
- Sindbis virus (SINV) is a model for age-dependent viral encephalitis.
- SINV is explored as a gene delivery vector for neural stem cells.
- The toxicity of SINV as a vector in human stem cells is understudied.
Purpose of the Study:
- To investigate human embryonic stem cell-derived neural progenitor cells (hNPCs) cellular responses to SINV infection.
- To assess SINV susceptibility, proliferation, cell death, and stemness markers in hNPCs.
- To evaluate SINV's impact on hNPCs plasticity and homeostasis.
Main Methods:
- Infection of hNPCs with SINV.
- Assessment of cell susceptibility to SINV.
- Analysis of cell proliferation and apoptosis markers.
- Examination of stemness marker expression in infected hNPCs.
Main Results:
- hNPCs exhibit high susceptibility to SINV infection.
- SINV infection induces apoptosis in hNPCs.
- Cell proliferation markers remain unaffected by SINV infection.
- SINV significantly alters key regulators of hNPCs plasticity and homeostasis.
Conclusions:
- hNPCs are a suitable model for studying viral-induced neurodevelopmental and degenerative diseases.
- SINV exhibits significant toxicity to hNPCs.
- Caution is advised when using SINV as a gene delivery vector for human stem cell lines.
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