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pmid:27293547
Bioinformatic analysis reveals the expression of unique transcriptomic signatures in Zika virus infected human neural stem cells.
Alyssa J Rolfe · Dale B Bosco · Jingying Wang · Richard S Nowakowski · Jianqing Fan · Yi Ren
Cell & bioscience · 2016 doi:10.1186/s13578-016-0110-x
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Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:27293547", "kind": "science-record", "revision": 4, "content_hash": "sha256:127b9938e85e90e3639c0d048f7b3bb0bf6f412e07e12d8927382dce2de60cba", "created_at": "2026-11-01T15:40:18Z", "updated_at": "2026-11-01T21:20:33Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Bioinformatic analysis reveals the expression of unique transcriptomic signatures in Zika virus infected human neural stem cells.", "doi": "10.1186/s13578-016-0110-x", "pmid": "27293547", "authors": ["Alyssa J Rolfe", "Dale B Bosco", "Jingying Wang", "Richard S Nowakowski", "Jianqing Fan", "Yi Ren"], "journal": "Cell & bioscience", "year": 2016, "abstract": "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.\nMETHODS: 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.\nRESULTS: 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.\nCONCLUSION: 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.", "claims": [{"id": "claim-method", "statement": "Comparison of the mock-infected samples to the ZIKV-infected samples using a modified t-test yields a total of 3443 genes up-regulated and 3421 down-regulated.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:27293547", "locator": "sections[3] \"Comprehensive gene set gene ontology analysis\" paragraph 2", "quote": "Comparison of the mock-infected samples to the ZIKV-infected samples using a modified t-test yields a total of 3443 genes up-regulated and 3421 down-regulated."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets supporting the conclusions of this article are available in the gene expression omnibus (GEO) repository, http://www.ncbi.nlm.nih.gov/geo/.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:27293547", "locator": "sections[13] \"Availability of data and materials\" paragraph 2", "quote": "The datasets supporting the conclusions of this article are available in the gene expression omnibus (GEO) repository, http://www.ncbi.nlm.nih.gov/geo/."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Using a modified t-test on ZIKV-infected hNPC RNA-seq data from GEO GSE78711, with GEO GSE35295 used for CMV comparison, the study found broad enrichment of pro-inflammatory and congenital nervous system pathways in ZIKV-infected hNPCs.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:27293547", "locator": "sections[3] \"Comprehensive gene set gene ontology analysis\" paragraph 2", "quote": "Comparison of the mock-infected samples to the ZIKV-infected samples using a modified t-test yields a total of 3443 genes up-regulated and 3421 down-regulated."}, {"asset": "source:pmid:27293547", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "We analyzed the transcriptomic sequencing (RNA-seq) data (GEO: GSE78711) of ZIKV (Strain: MR766) infected hNPCs."}, {"asset": "source:pmid:27293547", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "For comparison to the ZIKV-infected hNPCs, the expression data from hNPCs infected with human cytomegalovirus (CMV) (Strain: AD169) was used (GEO: GSE35295)."}, {"asset": "source:pmid:27293547", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "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."}, {"asset": "source:pmid:27293547", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "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."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Using a modified t-test on ZIKV-infected hNPC RNA-seq data from GEO GSE78711, with GEO GSE35295 used for CMV comparison, the study found broad enrichment of pro-inflammatory and congenital nervous system pathways in ZIKV-infected hNPCs.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:27293547"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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"−2.53145", "0.00005"], ["MFI2", "4241", "Antigen p97 (melanoma associated) identified by monoclonal antibodies 133.2 and 96.5", "−2.50748", "0.00005"], ["MAPK15", "225689", "Mitogen-activated protein kinase 15", "−2.46203", "0.00005"], ["C21orf58", "54058", "Chromosome 21 open reading frame 58", "−2.39697", "0.00005"], ["SPEF1", "25876", "Sperm flagellar 1", "−2.39565", "0.00005"], ["GHRL", "51738", "Ghrelin/obestatin prepropeptide", "−2.35804", "0.00805"], ["ATG16L2", "89849", "Autophagy related 16-like 2 (S. cerevisiae)", "−2.34225", "0.00005"], ["CXCL14", "9547", "Chemokine (C-X-C motif) ligand 14", "−2.33189", "0.0015"], ["SUSD2", "56241", "Sushi domain containing 2", "−2.28898", "0.00005"], ["C6orf118", "168090", "Chromosome 6 open reading frame 118", "−2.27987", "0.00005"], ["DLX6-AS1", "285987", "DLX6 antisense RNA 1", "−2.26662", "0.00005"], ["ADAM28", "10863", "ADAM metallopeptidase domain 28", "−2.25906", "0.00005"], ["NXPH2", "11249", "Neurexophilin 2", "−2.22856", "0.00005"], ["AQP7P1", "375719", "Aquaporin 7 pseudogene 1", "−2.2255", "0.00005"], ["EFCAB1", "79645", "EF-hand calcium binding domain 1", "−2.19918", "0.00005"], ["WNT8B", "7479", "Wingless-type MMTV integration site family, member 8B", "−2.19366", "0.00005"], ["PI15", "51050", "Peptidase inhibitor 15", "−2.17615", "0.00005"], ["C1orf189", "388701", "Chromosome 1 open reading frame 189", "−2.17531", "0.01255"], ["OLFML3", "56944", "Olfactomedin-like 3", "−2.16835", "0.0016"]], "row_count": 31, "column_count": 5, "numeric_cells": 129, "header_rows": 1, "locator": "section[3]/table-wrap[2]#Tab2"}}, {"id": "asset:table:pmid:27293547:3", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:6d81d5a8deee92ee9ec056944c517beb80bea8a1b1630bd2c71d94c11b3c81dd", "bytes": 3325, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[4]/table-wrap[1]#Tab3", "version": null, "note": "Neurological clinical phenotypes associated with ZIKV DEGs", "structure": {"pmcid": "PMC4902960", "section_index": 4, "section_title": "ZIKV DEGs represented in canonical human neurological diseases", "row_count": 62, "column_count": 3}, "table": {"label": "Table 3", "caption": "Neurological clinical phenotypes associated with ZIKV DEGs", "rows": [["Disease", "Gene symbol", "Gene name"], ["Microcephaly", "DYRK1A", "Dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A"], ["MCPH1", "Microcephalin 1"], ["CASK", "Calcium/calmodulin-dependent serine protein kinase (MAGUK family)"], ["PHGDH", "Phosphoglycerate dehydrogenase"], ["ARFGEF2", "ADP-ribosylation factor guanine nucleotide-exchange factor 2"], ["ASPM", "Asp (abnormal spindle) homolog, microcephaly associated"], ["CENPJ", "Centromere protein J"], ["CEP152", "Centrosomal protein 152 kDa"], ["SLC25A19", "Solute carrier family 25 (mitochondrial thiamine pyrophosphate carrier), member 19"], ["WDR62", "WD repeat domain 62"], ["CDK5RAP2", "CDK5 regulatory subunit associated protein 2"], ["CASC5", "Cancer susceptibility candidate 5"], ["NBN", "Nibrin"], ["EFTUD2", "Elongation factor Tu GTP binding domain containing 2"], ["IER3IP1", "Immediate early response 3 interacting protein 1"], ["STIL", "SCL/TAL1 interrupting locus"], ["CEP135", "Centrosomal protein 135 kDa"], ["ZNF335", "Zinc finger protein 335"], ["NDE1", "nudE nuclear distribution E homolog 1"], ["DIAPH1", "Diaphanous homolog 1"], ["KIF11", "Kinesin family member 11"], ["Congenital nervous system disorders", "MCPH1", "Microcephalin 1"], ["ARFGEF2", "ADP-ribosylation factor guanine nucleotide-exchange factor 2 (brefeldin A-inhibited)"], ["TGIF1", "TGFB-induced factor homeobox 1"], ["GRIN2B", "Glutamate receptor, ionotropic, N-methyl d-aspartate 2B"], ["SLC12A5", "Solute carrier family 12 (potassium/chloride transporter), member 5"], ["FLNA", "Filamin A, alpha"], ["SIX3", "SIX homeobox 3"], ["SHH", "Sonic hedgehog"], ["CDK5RAP2", "CDK5 regulatory subunit associated protein 2"], ["NDE1", "nudE nuclear distribution E homolog 1"], ["WDR62", "WD repeat domain 62"], ["ASPM", "Asp (abnormal spindle) homolog, microcephaly associated"], ["CENPJ", "Centromere protein J"], ["STIL", "SCL/TAL1 interrupting locus"], ["FKTN", "Fukutin"], ["POMGNT1", "Protein O−linked mannose beta1,2−N−acetylglucosaminyltransferase"], ["CEP152", "Centrosomal protein 152 kDa"], ["POMT2", "Protein−O−mannosyltransferase 2"], ["GLI2", "GLI family zinc finger 2"], ["ZNF335", "Zinc finger protein 335"], ["Epilepsy syndrome", "CDKL5", "Cyclin−dependent kinase−like 5"], ["CSTB", "Cystatin B (stefin B)"], ["TSC1", "Tuberous sclerosis 1"], ["CACNB4", "Calcium channel, voltage−dependent, beta 4 subunit"], ["CLCN2", "Chloride channel, voltage−sensitive 2"], ["PCDH19", "Protocadherin 19"], ["KCNQ2", "Potassium voltage−gated channel, KQT−like subfamily, member 2"], ["CLN5", "Ceroid−lipofuscinosis, neuronal 5"], ["ATP1A2", "ATPase, Na +/K + transporting, 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RESULTS: We analyzed RNA-sequencing data for transcript expression alterations i", "gested ZIKV target. METHODS: We analyzed the transcriptomic sequencing (RNA-seq) data (GEO: GSE78711) of"], "order_basis": "paper_text_order:11", "id": "assay:1"}, {"role": "data_generation", "definition_id": "apoptosis_assay", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.69, "evidence": ["), resulting in cell cycle abnormalities and apoptosis. Consequently, hNPCs are a suggested ZIKV ta"], "order_basis": "paper_text_order:712", "id": "assay:2"}]}