Zika Virus Infects Human Cortical Neural Progenitors and Attenuates Their Growth
Open accessAbstract
The suspected link between infection by Zika virus (ZIKV), a re-emerging flavivirus, and microcephaly is an urgent global health concern. The direct target cells of ZIKV in the developing human fetus are not clear. Here we show that a strain of the ZIKV, MR766, serially passaged in monkey and mosquito cells efficiently infects human neural progenitor cells (hNPCs) derived from induced pluripotent stem cells. Infected hNPCs further release infectious ZIKV particles. Importantly, ZIKV infection increases cell death and dysregulates cell-cycle progression, resulting in attenuated hNPC growth. Global gene expression analysis of infected hNPCs reveals transcriptional dysregulation, notably of cell-cycle-related pathways. Our results identify hNPCs as a direct ZIKV target. In addition, we establish a tractable experimental model system to investigate the impact and mechanism of ZIKV on human brain development and provide a platform to screen therapeutic compounds.
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One study using 2D iPSC-derived neural progenitor cells and two later studies using both 2D neural precursor cells and brain organoids demonstrated the association between Zika virus and neural progenitor targeting.
“A study using 2D iPSC-derived neural progenitor cells68 and two later studies69,70 that used both 2D neural precursor cells (NPCs) and brain organoids demonstrated this association.”
From The use of brain organoids to investigate neural development and disease (2017) · cites this paper as [68]
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Cites
Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources
Huang, D. W., Sherman, B. T., & Lempicki, R. A. (2009) · Nature Protocols · doi:10.1038/nprot.2008.211 · Cited by 35,890 · see citing works
Trapnell, C., Roberts, A., Goff, L. A., Pertea, G. M., Kim, D., Kelley, D. R., Pimentel, H., Salzberg, S. L., Rinn, J. L., & Pachter, L. S. (2012) · Nature Protocols · doi:10.1038/nprot.2012.016 · Cited by 11,930 · see citing works
Zika Virus Associated with Microcephaly
Mlakar, J., Korva, M., Tul, N., Popović, M., Poljšak-Prijatelj, M., Mraz, J., Kolenc, M., Resman Rus, K., Vesnaver Vipotnik, T., Fabjan Vodušek, V., et al. (2016) · New England Journal of Medicine · doi:10.1056/nejmoa1600651 · Cited by 2,884 · see citing works
Zika Virus (I). Isolations and serological specificity
Dick, G. W. A., Kitchen, S. F., & Haddow, A. J. (1952) · Transactions of the Royal Society of Tropical Medicine and Hygiene · doi:10.1016/0035-9203(52)90042-4 · Cited by 2,698 · see citing works
Biology of Zika Virus Infection in Human Skin Cells
Hamel, R., Dejarnac, O., Wichit, S., Ekchariyawat, P., Neyret, A., Luplertlop, N., Perera-Lecoin, M., Surasombatpattana, P., Talignani, L., Frédéric Thomas, A., et al. (2015) · Journal of Virology · doi:10.1128/jvi.00354-15 · Cited by 1,199 · see citing works
Calvet, G. A., Aguiar, R. S., Melo, A., Sampaio, S. A., de Filippis, I., Fabri, A. D. A., de Araújo, E. S. M., de Sequeira, P. C., de Mendonça, M. C. L., de Oliveira, L., et al. (2016) · The Lancet Infectious Diseases · doi:10.1016/s1473-3099(16)00095-5 · Cited by 1,164 · see citing works
Adult Mammalian Neural Stem Cells and Neurogenesis: Five Decades Later
Bond, A. M., Ming, G.-L., & Song, H. (2015) · Cell Stem Cell · doi:10.1016/j.stem.2015.09.003 · Cited by 791 · see citing works
Self-citationSynaptic dysregulation in a human iPS cell model of mental disorders
Wen, Z., Nguyen, H. N., Guo, Z., Lalli, M. A., Wang, X., Su, Y., Kim, N.-S., Yoon, K.-J., Shin, J., Zhang, C., et al. (2014) · Nature · doi:10.1038/nature13716 · Cited by 549 · see citing works
Self-citationWest Nile virus infection and immunity
Suthar, M. S., Diamond, M., & Gale, M. (2013) · Nature Reviews Microbiology · doi:10.1038/nrmicro2950 · Cited by 432 · see citing works
Zika virus and microcephaly: why is this situation a PHEIC?
Heymann, D. L., Hodgson, A., Sall, A. A., Freedman, D. O., Staples, J. E., Althabe, F., Baruah, K., Mahmud, G., Kandun, N., Vasconcelos, P. F. C., et al. (2016) · The Lancet · doi:10.1016/s0140-6736(16)00320-2 · Cited by 415 · see citing works
Petersen, E., Wilson, M. E., Touch, S., McCloskey, B., Mwaba, P., Bates, M., Dar, O. A., Mattes, F. M., Kidd, M., Ippolito, G., et al. (2016) · International Journal of Infectious Diseases · doi:10.1016/j.ijid.2016.02.001 · Cited by 362 · see citing works
Membranous Replication Factories Induced by Plus-Strand RNA Viruses
Romero‐Brey, I., & Bartenschlager, R. F. W. (2014) · Viruses · doi:10.3390/v6072826 · Cited by 275 · see citing works
Yoon, K.-J., Nguyen, H. N., Ursini, G., Zhang, F., Kim, N.-S., Wen, Z., Makri, G., Nauen, D., Shin, J. H., Park, Y., et al. (2014) · Cell Stem Cell · doi:10.1016/j.stem.2014.05.003 · Cited by 240 · see citing works
Self-citationZika virus infection of the central nervous system of mice
Bell, T., Field, E. J., & Narang, H. K. (1971) · Archives of Virology · doi:10.1007/bf01249709 · Cited by 213 · see citing works
Chiang, C.-H. J., Su, Y.-J., Wen, Z.-X., Yoritomo, N., Ross, C. A., Margolis, R., Song, H.-J., & Guo, L.-M. (2011) · Molecular Psychiatry · doi:10.1038/mp.2011.13 · Cited by 199 · see citing works
Self-citationWu, X., Robotham, J. M., Lee, E., Dalton, S., Kneteman, N. M., Gilbert, D. M., & Tang, H. (2012) · PLoS Pathogens · doi:10.1371/journal.ppat.1002617 · Cited by 166 · see citing works
Self-citationReplication in Cells of Hematopoietic Origin Is Necessary for Dengue Virus Dissemination
Pham, A. M., Langlois, R. A., & tenOever, B. R. (2012) · PLoS Pathogens · doi:10.1371/journal.ppat.1002465 · Cited by 96 · see citing works
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Azevedo, R. S. S., de Sousa, J. R., Araujo, M. T. F., Martins Filho, A. J., de Alcantara, B. N., Araujo, F. M. C., Queiroz, M. G. L., Cruz, A. C. R., Vasconcelos, B. H. B., Chiang, J. O., et al. (2018) · Scientific Reports · doi:10.1038/s41598-017-17765-5 · Cited by 3,478 · see citing works
Brain-Region-Specific Organoids Using Mini-bioreactors for Modeling ZIKV Exposure
Qian, X., Nguyen, H. N., Song, M. M., Hadiono, C., Ogden, S. C., Hammack, C., Yao, B., Hamersky, G. R., Jacob, F., Zhong, C., et al. (2016) · Cell · doi:10.1016/j.cell.2016.04.032 · Cited by 2,127 · see citing works
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Cugola, F. R., Fernandes, I. R., Russo, F. B., Freitas, B. C., Dias, J. L. M., Guimarães, K. P., Benazzato, C., Almeida, N., Pignatari, G. C., Romero, S., et al. (2016) · Nature · doi:10.1038/nature18296 · Cited by 1,326 · see citing works
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Garcez, P. P., Loiola, E. C., Madeiro da Costa, R., Higa, L. M., Trindade, P., Delvecchio, R., Nascimento, J. M., Brindeiro, R., Tanuri, A., & Rehen, S. K. (2016) · Science · doi:10.1126/science.aaf6116 · Cited by 1,184 · see citing works
A Mouse Model of Zika Virus Pathogenesis
Lazear, H. M., Govero, J., Smith, A. M., Platt, D. J., Fernandez, E., Miner, J. J., & Diamond, M. S. (2016) · Cell Host & Microbe · doi:10.1016/j.chom.2016.03.010 · Cited by 909 · see citing works
The use of brain organoids to investigate neural development and disease
Di Lullo, E., & Kriegstein, A. R. (2017) · Nature Reviews Neuroscience · doi:10.1038/nrn.2017.107 · Cited by 788 · see citing works
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Li, C., Xu, D., Ye, Q., Hong, S., Jiang, Y., Liu, X., Zhang, N., Shi, L., Qin, C.-F., & Xu, Z. (2016) · Cell Stem Cell · doi:10.1016/j.stem.2016.04.017 · Cited by 749 · see citing works
Dang, J., Tiwari, S. K., Lichinchi, G., Qin, Y., Patil, V. S., Eroshkin, A. M., & Rana, T. M. (2016) · Cell Stem Cell · doi:10.1016/j.stem.2016.04.014 · Cited by 731 · see citing works
Bershteyn, M., Nowakowski, T. J., Pollen, A. A., Di Lullo, E., Nene, A., Wynshaw-Boris, A., & Kriegstein, A. R. (2017) · Cell Stem Cell · doi:10.1016/j.stem.2016.12.007 · Cited by 566 · see citing works
Expression Analysis Highlights AXL as a Candidate Zika Virus Entry Receptor in Neural Stem Cells
Nowakowski, T. J., Pollen, A. A., Di Lullo, E., Sandoval-Espinosa, C., Bershteyn, M., & Kriegstein, A. R. (2016) · Cell Stem Cell · doi:10.1016/j.stem.2016.03.012 · Cited by 529 · see citing works
Zika virus cell tropism in the developing human brain and inhibition by azithromycin
Retallack, H., Di Lullo, E., Arias, C., Knopp, K. A., Laurie, M. T., Sandoval-Espinosa, C., Mancia Leon, W. R., Krencik, R., Ullian, E. M., Spatazza, J., et al. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1618029113 · Cited by 506 · see citing works
Induction of Expansion and Folding in Human Cerebral Organoids
Li, Y., Muffat, J., Omer, A., Bosch, I., Lancaster, M. A., Sur, M., Gehrke, L., Knoblich, J. A., & Jaenisch, R. (2017) · Cell Stem Cell · doi:10.1016/j.stem.2016.11.017 · Cited by 436 · see citing works
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Watanabe, M., Buth, J. E., Vishlaghi, N., de la Torre-Ubieta, L., Taxidis, J., Khakh, B. S., Coppola, G., Pearson, C. A., Yamauchi, K., Gong, D., et al. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.09.047 · Cited by 401 · see citing works
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Bredenoord, A. L., Clevers, H., & Knoblich, J. A. (2017) · Science · doi:10.1126/science.aaf9414 · Cited by 334 · see citing works
Building Models of Brain Disorders with Three-Dimensional Organoids
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Li, H., Saucedo-Cuevas, L., Regla-Nava, J. A., Chai, G., Sheets, N., Tang, W., Terskikh, A. V., Shresta, S., & Gleeson, J. G. (2016) · Cell stem cell · doi:10.1016/j.stem.2016.08.005 · Cited by 293 · see citing works
Onorati, M., Li, Z., Liu, F., Sousa, A. M. M., Nakagawa, N., Li, M., Dell’Anno, M. T., Gulden, F. O., Pochareddy, S., Tebbenkamp, A. T. N., et al. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.08.038 · Cited by 292 · see citing works
Wu, K.-Y., Zuo, G.-L., Li, X.-F., Ye, Q., Deng, Y.-Q., Huang, X.-Y., Cao, W.-C., Qin, C.-F., & Luo, Z.-G. (2016) · Cell Research · doi:10.1038/cr.2016.58 · Cited by 283 · see citing works
Wells, M. F., Salick, M. R., Wiskow, O., Ho, D. J., Worringer, K. A., Ihry, R. J., Kommineni, S., Bilican, B., Klim, J. R., Hill, E. J., et al. (2016) · Cell Stem Cell · doi:10.1016/j.stem.2016.11.011 · Cited by 269 · see citing works
Zhou, T., Tan, L., Cederquist, G. Y., Fan, Y., Hartley, B. J., Mukherjee, S., Tomishima, M., Brennand, K. J., Zhang, Q., Schwartz, R. E., et al. (2017) · Cell stem cell · doi:10.1016/j.stem.2017.06.017 · Cited by 263 · see citing works
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Hua, Y., Dai, X., Xu, Y., Xing, G., Liu, H., Lu, T., Chen, Y., & Zhang, Y. (2022) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2022.114239 · Cited by 232 · see citing works
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Lasso, G., Mayer, S. V., Winkelmann, E. R., Chu, T., Elliot, O., Patino-Galindo, J. A., Park, K., Rabadan, R., Honig, B., & Shapira, S. D. (2019) · Cell · doi:10.1016/j.cell.2019.08.005 · Cited by 133 · see citing works
Tristan, C. A., Ormanoglu, P., Slamecka, J., Malley, C., Chu, P.-H., Jovanovic, V. M., Gedik, Y., Jethmalani, Y., Bonney, C., Barnaeva, E., et al. (2021) · Stem Cell Reports · doi:10.1016/j.stemcr.2021.11.004 · Cited by 80 · see citing works
Contributions of maternal and fetal antiviral immunity in congenital disease
Yockey, L. J., Lucas, C., & Iwasaki, A. (2020) · Science · doi:10.1126/science.aaz1960 · Cited by 68 · see citing works
Long-term alterations in brain and behavior after postnatal Zika virus infection in infant macaques
Raper, J., Kovacs-Balint, Z., Mavigner, M., Gumber, S., Burke, M. W., Habib, J., Mattingly, C., Fair, D., Earl, E., Feczko, E., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-16320-7 · Cited by 67 · see citing works
Genome Editing in iPSC-Based Neural Systems: From Disease Models to Future Therapeutic Strategies
McTague, A., Rossignoli, G., Ferrini, A., Barral, S., & Kurian, M. A. (2021) · Frontiers in Genome Editing · doi:10.3389/fgeed.2021.630600 · Cited by 67 · see citing works
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Astick, M., & Vanderhaeghen, P. (2018) · Current Topics in Developmental Biology · doi:10.1016/bs.ctdb.2018.02.011 · Cited by 34 · see citing works
Overview on the Current Status of Zika Virus Pathogenesis and Animal Related Research
Pawitwar, S. S., Dhar, S., Tiwari, S., Ojha, C. R., Lapierre, J., Martins, K., Rodzinski, A., Parira, T., Paudel, I., Li, J., et al. (2017) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-017-9743-8 · Cited by 30 · see citing works
Advances in Cerebral Organoid Systems and their Application in Disease Modeling
Liu, F., Huang, J., Zhang, L., Chen, J., Zeng, Y., Tang, Y., & Liu, Z. (2019) · Neuroscience · doi:10.1016/j.neuroscience.2018.12.013 · Cited by 27 · see citing works
- Authors
- Tang, H., Hammack, C., Ogden, S. C., Wen, Z., Qian, X., Li, Y., Yao, B., Shin, J., Zhang, F., Lee, E. M., Christian, K. M., Didier, R. A., Jin, P., Song, H., & Ming, G.-L.
- Affiliations
- Florida State University (US)
- Johns Hopkins University (US)
- Emory University (US)
- Corresponding author
- Tang, Hengli
- Song, Hongjun
- Ming, Guo-li
- ORCID
- Venue
- Cell Stem Cell
- Publisher
- Elsevier BV
- Published
- 2016-05
- Volume
- 18
- Issue
- 5
- Pages
- 587-590
- ISSN
- 1875-9777 (ISSN-L)
- 1934-5909
- PMC
- PMC5299540
- OpenAlex
- W2292422784
- Cited by
- 1,292
- References
- 17
- Citations by year
- 2026: 37 · 2025: 55 · 2024: 52 · 2023: 77 · 2022: 96 · 2021: 128 · 2020: 130 · 2019: 139 · 2018: 159 · 2017: 224 · 2016: 192 · 2015: 2
- FWCI
- 234.63
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell stem cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Florida State University
- Directorate for Biological Sciences
- National Institute of Mental Health (R01MH102690)
- National Institute of Allergy and Infectious Diseases (R21AI119530, R21AI111250)
- National Institute of Neurological Disorders and Stroke (R01NS047344, R01NS048271, R21NS095348, R37NS047344, R56NS047344)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Mosquito-borne diseases and control
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Health Sciences › Medicine › Epidemiology › Virology and Viral Diseases
- Keywords
- Zika virus, neural progenitor cells, microcephaly, cell cycle dysregulation, cell death, iPSC-derived neurons, viral target cells, transcriptional dysregulation, brain development, flavivirus
- MeSH terms
- Zika Virus Infection, Zika Virus, Cell Cycle, Gene Expression Regulation, Humans, Cell Death, Cell Proliferation, Induced Pluripotent Stem Cells, Neural Stem Cells
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