Cellular responses to Sindbis virus infection of neural progenitors derived from human embryonic stem cells

Abstract

BackgroundSindbis 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.FindingsWe 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.ConclusionThe 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.

In Vitro Analyses of the Multifocal Effects of Natural Alkaloids Berberine, Matrine, and Tabersonine against the O’nyong-nyong Arthritogenic Alphavirus Infection and Inflammation

“…Its downregulation during ONNV infection was consistent with a previous report for SINV in vitro in human neural progenitor (hNPC) cells [65], and its upregulation occurred only with TAB. The downregulation of STAT3 gene expression was also established in vitro for SINV in hNPC [65], but our data were inconclusive. The NLRP3/caspase-1 pathway favors the strong pro-inflammatory mediator release (IL-18 and IL-1β) and pyroptosis [66] and is related to the severity of the alphavirus infection.…”

“…The MAPK pathway is involved in lifecycle of the cell and the inflammatory responses [ 64 ], and it was reported that CHIKV induced MAPK expression in human osteosarcoma (HOS) cells [ 45 ]. Its downregulation during ONNV infection was consistent with a previous report for SINV in vitro in human neural progenitor (hNPC) cells [ 65 ], and its upregulation occurred only with TAB. The downregulation of STAT3 gene expression was also established in vitro for SINV in hNPC [ 65 ], but our data were inconclusive.…”

Japanese encephalitis virus induces human neural stem/progenitor cell death by elevating GRP78, PHB and hnRNPC through ER stress

“… 11 We also confirmed the consequences of ER stress in hNS1 cells and found it as an executioner phenomenon leading to stem cell apoptosis. Evidences indicate neural stem cell death in many other cases of viral infection like Zika virus reducing viable number of cortical hNPCs, 12 Sindbis virus inducing apoptosis in hNPCs 13 and Cytomegalovirus promoting apoptosis in NSPCs following ER stress. 14 Zika virus is also reported to infect neural progenitors resulting in microcephaly.…”