Phenotypic Differences between Asian and African Lineage Zika Viruses in Human Neural Progenitor Cells

ABSTRACT Recent Zika virus (ZIKV) infections have been associated with a range of neurological complications, in particular congenital microcephaly. Human neural progenitor cells (hNPCs) are thought to play an important role in the pathogenesis of microcephaly, and experimental ZIKV infection of hNP...

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Autores principales:	Fatih Anfasa, Jurre Y. Siegers, Mark van der Kroeg, Noreen Mumtaz, V. Stalin Raj, Femke M. S. de Vrij, W. Widagdo, Gülsah Gabriel, Sara Salinas, Yannick Simonin, Chantal Reusken, Steven A. Kushner, Marion P. G. Koopmans, Bart Haagmans, Byron E. E. Martina, Debby van Riel
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2017
Materias:	African strains Asian strains growth kinetics human neural progenitor cells neuronal cells one-step growth curve Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/7de9006b5bb9498794ea49c3ad3ebc00
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spelling	oai:doaj.org-article:7de9006b5bb9498794ea49c3ad3ebc002021-11-15T15:22:04ZPhenotypic Differences between Asian and African Lineage Zika Viruses in Human Neural Progenitor Cells10.1128/mSphere.00292-172379-5042https://doaj.org/article/7de9006b5bb9498794ea49c3ad3ebc002017-08-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00292-17https://doaj.org/toc/2379-5042ABSTRACT Recent Zika virus (ZIKV) infections have been associated with a range of neurological complications, in particular congenital microcephaly. Human neural progenitor cells (hNPCs) are thought to play an important role in the pathogenesis of microcephaly, and experimental ZIKV infection of hNPCs has been shown to induce cell death. However, the infection efficiency and rate of cell death have varied between studies, which might be related to intrinsic differences between African and Asian lineage ZIKV strains. Therefore, we determined the replication kinetics, including infection efficiency, burst size, and ability to induce cell death, of two Asian and two African ZIKV strains. African ZIKV strains replicated to higher titers in Vero cells, human glioblastoma (U87MG) cells, human neuroblastoma (SK-N-SH) cells, and hNPCs than Asian ZIKV strains. Furthermore, infection with Asian ZIKV strains did not result in significant cell death early after infection, whereas infection with African ZIKV strains resulted in high percentages of cell death in hNPCs. The differences between African and Asian lineage ZIKV strains highlight the importance of including relevant ZIKV strains to study the pathogenesis of congenital microcephaly and caution against extrapolation of experimental data obtained using historical African ZIKV strains to the current outbreak. Finally, the fact that Asian ZIKV strains infect only a minority of cells with a relatively low burst size together with the lack of early cell death induction might contribute to its ability to cause chronic infections within the central nervous system (CNS). IMPORTANCE The mechanism by which ZIKV causes a range of neurological complications, especially congenital microcephaly, is not well understood. The fact that congenital microcephaly is associated with Asian lineage ZIKV strains raises the question of why this was not discovered earlier. One possible explanation is that Asian and African ZIKV strains differ in their abilities to infect cells of the CNS and to cause neurodevelopmental problems. Here, we show that Asian ZIKV strains infect and induce cell death in human neural progenitor cells—which are important target cells in the development of congenital microcephaly—less efficiently than African ZIKV strains. These features of Asian ZIKV strains likely contribute to their ability to cause chronic infections, often observed in congenital microcephaly cases. It is therefore likely that phenotypic differences between ZIKV strains could be, at least in part, responsible for the ability of Asian ZIKV strains to cause congenital microcephaly.Fatih AnfasaJurre Y. SiegersMark van der KroegNoreen MumtazV. Stalin RajFemke M. S. de VrijW. WidagdoGülsah GabrielSara SalinasYannick SimoninChantal ReuskenSteven A. KushnerMarion P. G. KoopmansBart HaagmansByron E. E. MartinaDebby van RielAmerican Society for MicrobiologyarticleAfrican strainsAsian strainsgrowth kineticshuman neural progenitor cellsneuronal cellsone-step growth curveMicrobiologyQR1-502ENmSphere, Vol 2, Iss 4 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	African strains Asian strains growth kinetics human neural progenitor cells neuronal cells one-step growth curve Microbiology QR1-502
spellingShingle	African strains Asian strains growth kinetics human neural progenitor cells neuronal cells one-step growth curve Microbiology QR1-502 Fatih Anfasa Jurre Y. Siegers Mark van der Kroeg Noreen Mumtaz V. Stalin Raj Femke M. S. de Vrij W. Widagdo Gülsah Gabriel Sara Salinas Yannick Simonin Chantal Reusken Steven A. Kushner Marion P. G. Koopmans Bart Haagmans Byron E. E. Martina Debby van Riel Phenotypic Differences between Asian and African Lineage Zika Viruses in Human Neural Progenitor Cells
description	ABSTRACT Recent Zika virus (ZIKV) infections have been associated with a range of neurological complications, in particular congenital microcephaly. Human neural progenitor cells (hNPCs) are thought to play an important role in the pathogenesis of microcephaly, and experimental ZIKV infection of hNPCs has been shown to induce cell death. However, the infection efficiency and rate of cell death have varied between studies, which might be related to intrinsic differences between African and Asian lineage ZIKV strains. Therefore, we determined the replication kinetics, including infection efficiency, burst size, and ability to induce cell death, of two Asian and two African ZIKV strains. African ZIKV strains replicated to higher titers in Vero cells, human glioblastoma (U87MG) cells, human neuroblastoma (SK-N-SH) cells, and hNPCs than Asian ZIKV strains. Furthermore, infection with Asian ZIKV strains did not result in significant cell death early after infection, whereas infection with African ZIKV strains resulted in high percentages of cell death in hNPCs. The differences between African and Asian lineage ZIKV strains highlight the importance of including relevant ZIKV strains to study the pathogenesis of congenital microcephaly and caution against extrapolation of experimental data obtained using historical African ZIKV strains to the current outbreak. Finally, the fact that Asian ZIKV strains infect only a minority of cells with a relatively low burst size together with the lack of early cell death induction might contribute to its ability to cause chronic infections within the central nervous system (CNS). IMPORTANCE The mechanism by which ZIKV causes a range of neurological complications, especially congenital microcephaly, is not well understood. The fact that congenital microcephaly is associated with Asian lineage ZIKV strains raises the question of why this was not discovered earlier. One possible explanation is that Asian and African ZIKV strains differ in their abilities to infect cells of the CNS and to cause neurodevelopmental problems. Here, we show that Asian ZIKV strains infect and induce cell death in human neural progenitor cells—which are important target cells in the development of congenital microcephaly—less efficiently than African ZIKV strains. These features of Asian ZIKV strains likely contribute to their ability to cause chronic infections, often observed in congenital microcephaly cases. It is therefore likely that phenotypic differences between ZIKV strains could be, at least in part, responsible for the ability of Asian ZIKV strains to cause congenital microcephaly.
format	article
author	Fatih Anfasa Jurre Y. Siegers Mark van der Kroeg Noreen Mumtaz V. Stalin Raj Femke M. S. de Vrij W. Widagdo Gülsah Gabriel Sara Salinas Yannick Simonin Chantal Reusken Steven A. Kushner Marion P. G. Koopmans Bart Haagmans Byron E. E. Martina Debby van Riel
author_facet	Fatih Anfasa Jurre Y. Siegers Mark van der Kroeg Noreen Mumtaz V. Stalin Raj Femke M. S. de Vrij W. Widagdo Gülsah Gabriel Sara Salinas Yannick Simonin Chantal Reusken Steven A. Kushner Marion P. G. Koopmans Bart Haagmans Byron E. E. Martina Debby van Riel
author_sort	Fatih Anfasa
title	Phenotypic Differences between Asian and African Lineage Zika Viruses in Human Neural Progenitor Cells
title_short	Phenotypic Differences between Asian and African Lineage Zika Viruses in Human Neural Progenitor Cells
title_full	Phenotypic Differences between Asian and African Lineage Zika Viruses in Human Neural Progenitor Cells
title_fullStr	Phenotypic Differences between Asian and African Lineage Zika Viruses in Human Neural Progenitor Cells
title_full_unstemmed	Phenotypic Differences between Asian and African Lineage Zika Viruses in Human Neural Progenitor Cells
title_sort	phenotypic differences between asian and african lineage zika viruses in human neural progenitor cells
publisher	American Society for Microbiology
publishDate	2017
url	https://doaj.org/article/7de9006b5bb9498794ea49c3ad3ebc00
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Phenotypic Differences between Asian and African Lineage Zika Viruses in Human Neural Progenitor Cells

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