BACKGROUND: The single-stranded RNA Flavivirus, Zika virus (ZIKV), has recently 
re-emerged and spread rapidly across the western hemisphere's equatorial 
countries, primarily through Aedes mosquito transmission. While symptoms in 
adult infections appear to be self-limiting and mild, severe birth defects, such 
as microcephaly, have been linked to infection during early pregnancy. Recently, 
Tang et al. (Cell Stem Cell 2016, doi: 10.1016/j.stem.2016.02.016) demonstrated 
that ZIKV efficiently infects induced pluripotent stem cell (iPSC) derived human 
neural progenitor cells (hNPCs), resulting in cell cycle abnormalities and 
apoptosis. Consequently, hNPCs are a suggested ZIKV target.
METHODS: We analyzed the transcriptomic sequencing (RNA-seq) data (GEO: 
GSE78711) of ZIKV (Strain: MR766) infected hNPCs. For comparison to the 
ZIKV-infected hNPCs, the expression data from hNPCs infected with human 
cytomegalovirus (CMV) (Strain: AD169) was used (GEO: GSE35295). Utilizing a 
combination of Gene Ontology, database of human diseases, and pathway analysis, 
we generated a putative systemic model of infection supported by known molecular 
pathways of other highly related viruses.
RESULTS: We analyzed RNA-sequencing data for transcript expression alterations 
in ZIKV-infected hNPCs, and then compared them to expression patterns of 
iPSC-derived hNPCs infected with CMV, a virus that can also induce severe 
congenital neurological defects in developing fetuses. We demonstrate for the 
first time that many of cellular pathways correlate with clinical pathologies 
following ZIKV infection such as microcephaly, congenital nervous system 
disorders and epilepsy. Furthermore, ZIKV activates several inflammatory signals 
within infected hNPCs that are implicated in innate and acquired immune 
responses, while CMV-infected hNPCs showed limited representation of these 
pathways. Moreover, several genes related to pathogen responses are 
significantly upregulated upon ZIKV infection, but not perturbed in CMV-infected 
hNPCs.
CONCLUSION: The presented study is the first to report enrichment of numerous 
pro-inflammatory pathways in ZIKV-infected hNPCs, indicating that hNPCs are 
capable of signaling through canonical pro-inflammatory pathways following viral 
infection. By defining gene expression profiles, new factors in the pathogenesis 
of ZIKV were identified which could help develop new therapeutic strategies.