Infectivity in full-term placenta of Zika viruses with different lipid profiles

Among flaviviruses, Zika virus (ZIKV) is the only arbovirus officially recognized as a teratogenic agent, as a consequence of its ability to infect and cross the placental barrier causing congenital malformation in the fetus. While many studies have focused on understanding ZIKV pathogenesis during...

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Main Authors: Eva Mazzetto, Alessio Bortolami, Davide Bovo, Matteo Stocchero, Elisa Mazzacan, Alessandra Napolitan, Valentina Panzarin, Maria Rosa Tran, Gianpiero Zamperin, Adelaide Milani, Andrea Fortin, Michela Bigolaro, Paola Pirillo, Matteo Pagliari, Claudia Zanardello, Giuseppe Giordano, Maria Teresa Gervasi, Eugenio Baraldi, Calogero Terregino, Carlo Giaquinto, Francesco Bonfante
Format: Article
Language:English
Published: Elsevier 2025-02-01
Series:Virus Research
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Online Access:http://www.sciencedirect.com/science/article/pii/S0168170224002119
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author Eva Mazzetto
Alessio Bortolami
Davide Bovo
Matteo Stocchero
Elisa Mazzacan
Alessandra Napolitan
Valentina Panzarin
Maria Rosa Tran
Gianpiero Zamperin
Adelaide Milani
Andrea Fortin
Michela Bigolaro
Paola Pirillo
Matteo Pagliari
Claudia Zanardello
Giuseppe Giordano
Maria Teresa Gervasi
Eugenio Baraldi
Calogero Terregino
Carlo Giaquinto
Francesco Bonfante
author_facet Eva Mazzetto
Alessio Bortolami
Davide Bovo
Matteo Stocchero
Elisa Mazzacan
Alessandra Napolitan
Valentina Panzarin
Maria Rosa Tran
Gianpiero Zamperin
Adelaide Milani
Andrea Fortin
Michela Bigolaro
Paola Pirillo
Matteo Pagliari
Claudia Zanardello
Giuseppe Giordano
Maria Teresa Gervasi
Eugenio Baraldi
Calogero Terregino
Carlo Giaquinto
Francesco Bonfante
author_sort Eva Mazzetto
collection DOAJ
description Among flaviviruses, Zika virus (ZIKV) is the only arbovirus officially recognized as a teratogenic agent, as a consequence of its ability to infect and cross the placental barrier causing congenital malformation in the fetus. While many studies have focused on understanding ZIKV pathogenesis during pregnancy, the viral mechanisms affecting fetal development remain largely unclear. In this study, we investigated ZIKV virulence in placental trophoblasts, using viruses with distinct lipid profiles. Firstly, we propagated a ZIKV strain belonging to the Asian lineage in either mammalian or mosquito cells, obtaining two viral stocks, which were purified and analyzed to determine their genetic and lipid composition. Successively, we assessed the infectivity of the two stocks in placental cells using both immortalized cell lines and explants. We found that the two viral stocks displayed identical consensus sequences with homogeneous quasispecies composition. However, the lipid composition of their envelope significantly varied depending on the cell of origin, with the mammalian-derived viral stock characterized by a higher content of phosphatidylcholines compared to the virions originating from mosquito cells. Notably, ZIKV stock derived from mammalian cells showed a higher infectivity in immortalized villous trophoblasts and full-term placental explants of human origin. This increased infectivity was linked to enhanced fusion efficiency during the viral uncoating phase in trophoblast cells, as demonstrated using a lipophilic probe. Collectively, our data suggest a potential role of viral lipids as determinants of ZIKV infectivity in full-term placenta, underscoring the importance of lipidomic research in virology.
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spelling doaj-art-9129a0211dec41f39df7beb9124d788a2025-01-29T04:59:54ZengElsevierVirus Research1872-74922025-02-01352199518Infectivity in full-term placenta of Zika viruses with different lipid profilesEva Mazzetto0Alessio Bortolami1Davide Bovo2Matteo Stocchero3Elisa Mazzacan4Alessandra Napolitan5Valentina Panzarin6Maria Rosa Tran7Gianpiero Zamperin8Adelaide Milani9Andrea Fortin10Michela Bigolaro11Paola Pirillo12Matteo Pagliari13Claudia Zanardello14Giuseppe Giordano15Maria Teresa Gervasi16Eugenio Baraldi17Calogero Terregino18Carlo Giaquinto19Francesco Bonfante20Department of Women's and Children's Health, Padua University, Padova (PD), Italy; Department of Virology, Istituto Zooprofilattico Sperimentale delle Venezie, Legnaro (PD), Italy; Corresponding author.Department of Virology, Istituto Zooprofilattico Sperimentale delle Venezie, Legnaro (PD), ItalyLaboratory of Mass Spectrometry and Metabolomics, Department of Women's and Children's Health, Padua University, Padova (PD), ItalyDepartment of Women's and Children's Health, Padua University, Padova (PD), Italy; Laboratory of Mass Spectrometry and Metabolomics, Department of Women's and Children's Health, Padua University, Padova (PD), ItalyDepartment of Virology, Istituto Zooprofilattico Sperimentale delle Venezie, Legnaro (PD), ItalyDepartment of Virology, Istituto Zooprofilattico Sperimentale delle Venezie, Legnaro (PD), ItalyDepartment of Research and Innovation, Istituto Zooprofilattico Sperimentale delle Venezie, Legnaro (PD), ItalyGynaecology and Obstetrics Unit, Department of Women's and Children's Health, Padua University, Padova (PD), ItalyDepartment of Research and Innovation, Istituto Zooprofilattico Sperimentale delle Venezie, Legnaro (PD), ItalyDepartment of Research and Innovation, Istituto Zooprofilattico Sperimentale delle Venezie, Legnaro (PD), ItalyDepartment of Research and Innovation, Istituto Zooprofilattico Sperimentale delle Venezie, Legnaro (PD), ItalyDepartment of Diagnostic Services, Histopathology, Parasitology, Istituto Zooprofilattico Sperimentale delle Venezie, Legnaro (PD), ItalyDepartment of Women's and Children's Health, Padua University, Padova (PD), Italy; Laboratory of Mass Spectrometry and Metabolomics, Department of Women's and Children's Health, Padua University, Padova (PD), ItalyDepartment of Women's and Children's Health, Padua University, Padova (PD), Italy; Department of Virology, Istituto Zooprofilattico Sperimentale delle Venezie, Legnaro (PD), ItalyDepartment of Diagnostic Services, Histopathology, Parasitology, Istituto Zooprofilattico Sperimentale delle Venezie, Legnaro (PD), ItalyDepartment of Women's and Children's Health, Padua University, Padova (PD), Italy; Laboratory of Mass Spectrometry and Metabolomics, Department of Women's and Children's Health, Padua University, Padova (PD), ItalyGynaecology and Obstetrics Unit, Department of Women's and Children's Health, Padua University, Padova (PD), ItalyDepartment of Women's and Children's Health, Padua University, Padova (PD), Italy; Laboratory of Mass Spectrometry and Metabolomics, Department of Women's and Children's Health, Padua University, Padova (PD), ItalyDepartment of Virology, Istituto Zooprofilattico Sperimentale delle Venezie, Legnaro (PD), ItalyDepartment of Women's and Children's Health, Padua University, Padova (PD), ItalyDepartment of Virology, Istituto Zooprofilattico Sperimentale delle Venezie, Legnaro (PD), ItalyAmong flaviviruses, Zika virus (ZIKV) is the only arbovirus officially recognized as a teratogenic agent, as a consequence of its ability to infect and cross the placental barrier causing congenital malformation in the fetus. While many studies have focused on understanding ZIKV pathogenesis during pregnancy, the viral mechanisms affecting fetal development remain largely unclear. In this study, we investigated ZIKV virulence in placental trophoblasts, using viruses with distinct lipid profiles. Firstly, we propagated a ZIKV strain belonging to the Asian lineage in either mammalian or mosquito cells, obtaining two viral stocks, which were purified and analyzed to determine their genetic and lipid composition. Successively, we assessed the infectivity of the two stocks in placental cells using both immortalized cell lines and explants. We found that the two viral stocks displayed identical consensus sequences with homogeneous quasispecies composition. However, the lipid composition of their envelope significantly varied depending on the cell of origin, with the mammalian-derived viral stock characterized by a higher content of phosphatidylcholines compared to the virions originating from mosquito cells. Notably, ZIKV stock derived from mammalian cells showed a higher infectivity in immortalized villous trophoblasts and full-term placental explants of human origin. This increased infectivity was linked to enhanced fusion efficiency during the viral uncoating phase in trophoblast cells, as demonstrated using a lipophilic probe. Collectively, our data suggest a potential role of viral lipids as determinants of ZIKV infectivity in full-term placenta, underscoring the importance of lipidomic research in virology.http://www.sciencedirect.com/science/article/pii/S0168170224002119ZIKVLipidsPlacentaExplantsLipidomic
spellingShingle Eva Mazzetto
Alessio Bortolami
Davide Bovo
Matteo Stocchero
Elisa Mazzacan
Alessandra Napolitan
Valentina Panzarin
Maria Rosa Tran
Gianpiero Zamperin
Adelaide Milani
Andrea Fortin
Michela Bigolaro
Paola Pirillo
Matteo Pagliari
Claudia Zanardello
Giuseppe Giordano
Maria Teresa Gervasi
Eugenio Baraldi
Calogero Terregino
Carlo Giaquinto
Francesco Bonfante
Infectivity in full-term placenta of Zika viruses with different lipid profiles
Virus Research
ZIKV
Lipids
Placenta
Explants
Lipidomic
title Infectivity in full-term placenta of Zika viruses with different lipid profiles
title_full Infectivity in full-term placenta of Zika viruses with different lipid profiles
title_fullStr Infectivity in full-term placenta of Zika viruses with different lipid profiles
title_full_unstemmed Infectivity in full-term placenta of Zika viruses with different lipid profiles
title_short Infectivity in full-term placenta of Zika viruses with different lipid profiles
title_sort infectivity in full term placenta of zika viruses with different lipid profiles
topic ZIKV
Lipids
Placenta
Explants
Lipidomic
url http://www.sciencedirect.com/science/article/pii/S0168170224002119
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