Differential Type 1 IFN Gene Expression in CD14+ Placenta Cells Elicited by Zika Virus Infection During Pregnancy

Zika virus (ZIKV) is an arthropod-borne Flavivirus that can also be transmitted vertically from infected mother to fetus. Infection of the fetus during pregnancy can lead to congenital malformations and severely impact fetal brain development causing a myriad of diseases now labeled Congenital Zika...

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Autores principales:	Nicole N. Haese, Hannah Smith, Kosiso Onwuzu, Craig N. Kreklywich, Jessica L. Smith, Michael Denton, Nicholas Kreklywich, Aaron D. Streblow, Antonio E. Frias, Terry K. Morgan, Alec J. Hirsch, Benjamin N. Bimber, Victoria H. J. Roberts, Daniel N. Streblow
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	Zika virus pregnancy monocyte macrophage interferon Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/0b1682a400b24b2bbf2004af064df1b4
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spelling	oai:doaj.org-article:0b1682a400b24b2bbf2004af064df1b42021-12-01T13:24:28ZDifferential Type 1 IFN Gene Expression in CD14+ Placenta Cells Elicited by Zika Virus Infection During Pregnancy2673-818X10.3389/fviro.2021.783407https://doaj.org/article/0b1682a400b24b2bbf2004af064df1b42021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fviro.2021.783407/fullhttps://doaj.org/toc/2673-818XZika virus (ZIKV) is an arthropod-borne Flavivirus that can also be transmitted vertically from infected mother to fetus. Infection of the fetus during pregnancy can lead to congenital malformations and severely impact fetal brain development causing a myriad of diseases now labeled Congenital Zika Syndrome (CZS). The mechanisms by which ZIKV crosses the placenta into the fetal circulation and the extent of ZIKV-induced changes remain unclear. We have previously shown that ZIKV infection of pregnant rhesus macaques results in abnormal oxygen transport across the placenta which may promote uterine vasculitis and placental villous damage. Changes in immune cell frequencies and activation status were also detected, as were distinct changes in the proportions of CD14+ cell subsets with an altered ratio of classical to non-classical CD14+ monocyte cells in both the maternal decidua and placental villous from ZIKV-infected animals compare to uninfected controls. In the current study, we performed single cell RNA sequencing on CD14+ cells isolated from the decidua of animals that were ZIKV infected at 31, 51, or 115 days of gestation (where term is ~168 days) compared to pregnant, time-matched uninfected controls. Bioinformatic analysis identified unique transcriptional phenotypes between CD14+ cells of infected and uninfected animals suggesting a distinct and sustained difference in transcriptomes between infected and uninfected CD14+ cells derived from the decidua. The timing of ZIKV infection had no effect on the CD14+ cell transcriptional profiles. Interestingly, ZIKV infection caused changes in expression of genes in pathways related to cellular stress and metabolism as well as immune response activation. Type 1 interferon response genes (ISGs) were among those that were differentially expressed following infection and these included members of the ISG12 family, IFI27 and IFI6. These ISGs have been recently described as effectors of the IFN response to flaviviruses. Supplementing our animal findings, in CD14+ cells isolated from human placenta, ZIKV infection similarly induced the expression of IFI27 and IFI6. Overall, our results showed that ZIKV infection during pregnancy induces the stable expression of antiviral genes within CD14+ cells of the placenta, which may provide an immune shield to protect the placenta from further infection and damage.Nicole N. HaeseHannah SmithKosiso OnwuzuCraig N. KreklywichJessica L. SmithMichael DentonNicholas KreklywichAaron D. StreblowAntonio E. FriasAntonio E. FriasTerry K. MorganTerry K. MorganAlec J. HirschAlec J. HirschBenjamin N. BimberBenjamin N. BimberVictoria H. J. RobertsDaniel N. StreblowDaniel N. StreblowFrontiers Media S.A.articleZika viruspregnancymonocytemacrophageinterferonMicrobiologyQR1-502ENFrontiers in Virology, Vol 1 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Zika virus pregnancy monocyte macrophage interferon Microbiology QR1-502
spellingShingle	Zika virus pregnancy monocyte macrophage interferon Microbiology QR1-502 Nicole N. Haese Hannah Smith Kosiso Onwuzu Craig N. Kreklywich Jessica L. Smith Michael Denton Nicholas Kreklywich Aaron D. Streblow Antonio E. Frias Antonio E. Frias Terry K. Morgan Terry K. Morgan Alec J. Hirsch Alec J. Hirsch Benjamin N. Bimber Benjamin N. Bimber Victoria H. J. Roberts Daniel N. Streblow Daniel N. Streblow Differential Type 1 IFN Gene Expression in CD14+ Placenta Cells Elicited by Zika Virus Infection During Pregnancy
description	Zika virus (ZIKV) is an arthropod-borne Flavivirus that can also be transmitted vertically from infected mother to fetus. Infection of the fetus during pregnancy can lead to congenital malformations and severely impact fetal brain development causing a myriad of diseases now labeled Congenital Zika Syndrome (CZS). The mechanisms by which ZIKV crosses the placenta into the fetal circulation and the extent of ZIKV-induced changes remain unclear. We have previously shown that ZIKV infection of pregnant rhesus macaques results in abnormal oxygen transport across the placenta which may promote uterine vasculitis and placental villous damage. Changes in immune cell frequencies and activation status were also detected, as were distinct changes in the proportions of CD14+ cell subsets with an altered ratio of classical to non-classical CD14+ monocyte cells in both the maternal decidua and placental villous from ZIKV-infected animals compare to uninfected controls. In the current study, we performed single cell RNA sequencing on CD14+ cells isolated from the decidua of animals that were ZIKV infected at 31, 51, or 115 days of gestation (where term is ~168 days) compared to pregnant, time-matched uninfected controls. Bioinformatic analysis identified unique transcriptional phenotypes between CD14+ cells of infected and uninfected animals suggesting a distinct and sustained difference in transcriptomes between infected and uninfected CD14+ cells derived from the decidua. The timing of ZIKV infection had no effect on the CD14+ cell transcriptional profiles. Interestingly, ZIKV infection caused changes in expression of genes in pathways related to cellular stress and metabolism as well as immune response activation. Type 1 interferon response genes (ISGs) were among those that were differentially expressed following infection and these included members of the ISG12 family, IFI27 and IFI6. These ISGs have been recently described as effectors of the IFN response to flaviviruses. Supplementing our animal findings, in CD14+ cells isolated from human placenta, ZIKV infection similarly induced the expression of IFI27 and IFI6. Overall, our results showed that ZIKV infection during pregnancy induces the stable expression of antiviral genes within CD14+ cells of the placenta, which may provide an immune shield to protect the placenta from further infection and damage.
format	article
author	Nicole N. Haese Hannah Smith Kosiso Onwuzu Craig N. Kreklywich Jessica L. Smith Michael Denton Nicholas Kreklywich Aaron D. Streblow Antonio E. Frias Antonio E. Frias Terry K. Morgan Terry K. Morgan Alec J. Hirsch Alec J. Hirsch Benjamin N. Bimber Benjamin N. Bimber Victoria H. J. Roberts Daniel N. Streblow Daniel N. Streblow
author_facet	Nicole N. Haese Hannah Smith Kosiso Onwuzu Craig N. Kreklywich Jessica L. Smith Michael Denton Nicholas Kreklywich Aaron D. Streblow Antonio E. Frias Antonio E. Frias Terry K. Morgan Terry K. Morgan Alec J. Hirsch Alec J. Hirsch Benjamin N. Bimber Benjamin N. Bimber Victoria H. J. Roberts Daniel N. Streblow Daniel N. Streblow
author_sort	Nicole N. Haese
title	Differential Type 1 IFN Gene Expression in CD14+ Placenta Cells Elicited by Zika Virus Infection During Pregnancy
title_short	Differential Type 1 IFN Gene Expression in CD14+ Placenta Cells Elicited by Zika Virus Infection During Pregnancy
title_full	Differential Type 1 IFN Gene Expression in CD14+ Placenta Cells Elicited by Zika Virus Infection During Pregnancy
title_fullStr	Differential Type 1 IFN Gene Expression in CD14+ Placenta Cells Elicited by Zika Virus Infection During Pregnancy
title_full_unstemmed	Differential Type 1 IFN Gene Expression in CD14+ Placenta Cells Elicited by Zika Virus Infection During Pregnancy
title_sort	differential type 1 ifn gene expression in cd14+ placenta cells elicited by zika virus infection during pregnancy
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/0b1682a400b24b2bbf2004af064df1b4
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Differential Type 1 IFN Gene Expression in CD14+ Placenta Cells Elicited by Zika Virus Infection During Pregnancy

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