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

Jie Xu,Rodney J Nash,Teryl K Frey

doi:10.1186/1756-0500-7-757

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.

Highlights

Sindbis virus (SINV) causes age-dependent encephalitis in mice, and serves as a model to study viral encephalitis
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
Findings hNPCs are fully permissive to SINV infection To determine the permissiveness of hNPCs to SINV infection, we plated them onto Matrigel-coated plates and infected them with SINV at an m.o.i of 1

Summary

Introduction

Sindbis virus (SINV) causes age-dependent encephalitis in mice, and 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; the toxicity and side effects of this vector have rarely been discussed. Sindbis virus (SINV), a positive strand RNA virus in the genus Alphavirus of the Togaviridae family, causes rash and fever in humans and age-dependent encephalitis in mice. The high and rapid expression of foreign genes from SINV vector is accomplished at the cost of shutting off protein nsP2 synthesis in the infected host cells. As SINV gains popularity in neurotherapy as an ideal vector for gene transfer into neural stem/progenitor cells, the toxicity, as well as other side effects of these vectors, needs to be addressed [3,10]

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