Zika Virus Requires the Expression of Claudin-7 for Optimal Replication in Human Endothelial Cells
Zika virus (ZIKV) infection has been associated with a series of neurological pathologies. In patients with ZIKV-induced neurological disorders, the virus is detectable in the central nervous system. Thus, ZIKV is capable of neuroinvasion, presumably through infection of the endothelial cells that c...
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doaj-73ad345137a8441aba427fd784e266b12021-09-20T05:50:09ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2021-09-011210.3389/fmicb.2021.746589746589Zika Virus Requires the Expression of Claudin-7 for Optimal Replication in Human Endothelial CellsJim Zoladek0Vincent Legros1Vincent Legros2Patricia Jeannin3Maxime Chazal4Nathalie Pardigon5Pierre-Emmanuel Ceccaldi6Antoine Gessain7Nolwenn Jouvenet8Philippe V. Afonso9Unité Épidémiologie et Physiopathologie des Virus Oncogènes, Institut Pasteur, Centre National de la Recherche Scientifique UMR 3569, Université de Paris, Paris, FranceUnité Épidémiologie et Physiopathologie des Virus Oncogènes, Institut Pasteur, Centre National de la Recherche Scientifique UMR 3569, Université de Paris, Paris, FranceVetAgro Sup, Centre International de Recherche en Infectiologie (CIRI), Lyon, FranceUnité Épidémiologie et Physiopathologie des Virus Oncogènes, Institut Pasteur, Centre National de la Recherche Scientifique UMR 3569, Université de Paris, Paris, FranceUnité Signalisation Antivirale, Institut Pasteur, Centre National de la Recherche Scientifique UMR 3569, Paris, FranceGroupe Arbovirus, Unité Environnement et Risques Infectieux, Institut Pasteur, Paris, FranceUnité Épidémiologie et Physiopathologie des Virus Oncogènes, Institut Pasteur, Centre National de la Recherche Scientifique UMR 3569, Université de Paris, Paris, FranceUnité Épidémiologie et Physiopathologie des Virus Oncogènes, Institut Pasteur, Centre National de la Recherche Scientifique UMR 3569, Université de Paris, Paris, FranceUnité Signalisation Antivirale, Institut Pasteur, Centre National de la Recherche Scientifique UMR 3569, Paris, FranceUnité Épidémiologie et Physiopathologie des Virus Oncogènes, Institut Pasteur, Centre National de la Recherche Scientifique UMR 3569, Université de Paris, Paris, FranceZika virus (ZIKV) infection has been associated with a series of neurological pathologies. In patients with ZIKV-induced neurological disorders, the virus is detectable in the central nervous system. Thus, ZIKV is capable of neuroinvasion, presumably through infection of the endothelial cells that constitute the blood-brain barrier (BBB). We demonstrate that susceptibility of BBB endothelial cells to ZIKV infection is modulated by the expression of tight-junction protein claudin-7 (CLDN7). Downregulation of CLDN7 reduced viral RNA yield, viral protein production, and release of infectious viral particles in several endothelial cell types, but not in epithelial cells, indicating that CLDN7 implication in viral infection is cell-type specific. The proviral activity of CLDN7 in endothelial cells is ZIKV-specific since related flaviviruses were not affected by CLDN7 downregulation. Together, our data suggest that CLDN7 facilitates ZIKV infection in endothelial cells at a post-internalization stage and prior to RNA production. Our work contributes to a better understanding of the mechanisms exploited by ZIKV to efficiently infect and replicate in endothelial cells and thus of its ability to cross the BBB.https://www.frontiersin.org/articles/10.3389/fmicb.2021.746589/fullflavivirusZika virusclaudinendothelial cellsinfectionblood-brain barrier |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jim Zoladek Vincent Legros Vincent Legros Patricia Jeannin Maxime Chazal Nathalie Pardigon Pierre-Emmanuel Ceccaldi Antoine Gessain Nolwenn Jouvenet Philippe V. Afonso |
spellingShingle |
Jim Zoladek Vincent Legros Vincent Legros Patricia Jeannin Maxime Chazal Nathalie Pardigon Pierre-Emmanuel Ceccaldi Antoine Gessain Nolwenn Jouvenet Philippe V. Afonso Zika Virus Requires the Expression of Claudin-7 for Optimal Replication in Human Endothelial Cells Frontiers in Microbiology flavivirus Zika virus claudin endothelial cells infection blood-brain barrier |
author_facet |
Jim Zoladek Vincent Legros Vincent Legros Patricia Jeannin Maxime Chazal Nathalie Pardigon Pierre-Emmanuel Ceccaldi Antoine Gessain Nolwenn Jouvenet Philippe V. Afonso |
author_sort |
Jim Zoladek |
title |
Zika Virus Requires the Expression of Claudin-7 for Optimal Replication in Human Endothelial Cells |
title_short |
Zika Virus Requires the Expression of Claudin-7 for Optimal Replication in Human Endothelial Cells |
title_full |
Zika Virus Requires the Expression of Claudin-7 for Optimal Replication in Human Endothelial Cells |
title_fullStr |
Zika Virus Requires the Expression of Claudin-7 for Optimal Replication in Human Endothelial Cells |
title_full_unstemmed |
Zika Virus Requires the Expression of Claudin-7 for Optimal Replication in Human Endothelial Cells |
title_sort |
zika virus requires the expression of claudin-7 for optimal replication in human endothelial cells |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Microbiology |
issn |
1664-302X |
publishDate |
2021-09-01 |
description |
Zika virus (ZIKV) infection has been associated with a series of neurological pathologies. In patients with ZIKV-induced neurological disorders, the virus is detectable in the central nervous system. Thus, ZIKV is capable of neuroinvasion, presumably through infection of the endothelial cells that constitute the blood-brain barrier (BBB). We demonstrate that susceptibility of BBB endothelial cells to ZIKV infection is modulated by the expression of tight-junction protein claudin-7 (CLDN7). Downregulation of CLDN7 reduced viral RNA yield, viral protein production, and release of infectious viral particles in several endothelial cell types, but not in epithelial cells, indicating that CLDN7 implication in viral infection is cell-type specific. The proviral activity of CLDN7 in endothelial cells is ZIKV-specific since related flaviviruses were not affected by CLDN7 downregulation. Together, our data suggest that CLDN7 facilitates ZIKV infection in endothelial cells at a post-internalization stage and prior to RNA production. Our work contributes to a better understanding of the mechanisms exploited by ZIKV to efficiently infect and replicate in endothelial cells and thus of its ability to cross the BBB. |
topic |
flavivirus Zika virus claudin endothelial cells infection blood-brain barrier |
url |
https://www.frontiersin.org/articles/10.3389/fmicb.2021.746589/full |
work_keys_str_mv |
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