Genetic and Functional Characterization of Congenital HCMV Clinical Strains in Ex Vivo First Trimester Placental Model
Human cytomegalovirus (HCMV) is the leading cause of congenital viral infection, leading to a variety of symptoms in the unborn child that range from asymptomatic to death in utero. Our objective was to better understand the mechanisms of placental infection by HCMV clinical strains, particularly du...
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MDPI AG
2023-07-01
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| Series: | Pathogens |
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| Online Access: | https://www.mdpi.com/2076-0817/12/8/985 |
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| author | Deborah Andouard Valentin Tilloy Elodie Ribot Melissa Mayeras Daniel Diaz-Gonzalez Chahrazed El Hamel Fabienne Piras-Douce Nathalie Mantel Sophie Alain |
| author_facet | Deborah Andouard Valentin Tilloy Elodie Ribot Melissa Mayeras Daniel Diaz-Gonzalez Chahrazed El Hamel Fabienne Piras-Douce Nathalie Mantel Sophie Alain |
| author_sort | Deborah Andouard |
| collection | DOAJ |
| description | Human cytomegalovirus (HCMV) is the leading cause of congenital viral infection, leading to a variety of symptoms in the unborn child that range from asymptomatic to death in utero. Our objective was to better understand the mechanisms of placental infection by HCMV clinical strains, particularly during the first trimester of pregnancy. We thus characterized and compared the replication kinetics of various HCMV clinical strains and laboratory strains by measuring viral loads in an ex vivo model of first trimester villi and decidua, and used NGS and PCA analysis to analyze the genes involved in cell tropism and virulence factors. We observed that first trimester villi and decidua are similarly permissive to laboratory and symptomatic strains, and that asymptomatic strains poorly replicate in decidua tissue. PCA analysis allowed us to segregate our clinical strains based on their clinical characteristics, suggesting a link between gene mutations and symptoms. All these results bring forth elements that can help better understand the mechanisms that induce the appearance of symptoms or in the congenitally infected newborn. |
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| institution | Directory Open Access Journal |
| issn | 2076-0817 |
| language | English |
| last_indexed | 2024-03-10T23:40:40Z |
| publishDate | 2023-07-01 |
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| series | Pathogens |
| spelling | doaj.art-8fb319e4c9fb489b86c9cb5ab479ad802023-11-19T02:31:47ZengMDPI AGPathogens2076-08172023-07-0112898510.3390/pathogens12080985Genetic and Functional Characterization of Congenital HCMV Clinical Strains in Ex Vivo First Trimester Placental ModelDeborah Andouard0Valentin Tilloy1Elodie Ribot2Melissa Mayeras3Daniel Diaz-Gonzalez4Chahrazed El Hamel5Fabienne Piras-Douce6Nathalie Mantel7Sophie Alain8Bacteriology-Virology-Hygien Department, National Reference Center for Herpesviruses, Centre Hospitalier Universitaire de Limoges, 87000 Limoges, FranceBacteriology-Virology-Hygien Department, National Reference Center for Herpesviruses, Centre Hospitalier Universitaire de Limoges, 87000 Limoges, FranceBacteriology-Virology-Hygien Department, National Reference Center for Herpesviruses, Centre Hospitalier Universitaire de Limoges, 87000 Limoges, FranceBacteriology-Virology-Hygien Department, National Reference Center for Herpesviruses, Centre Hospitalier Universitaire de Limoges, 87000 Limoges, FranceRESINFIT—Antimicrobials: Molecular Supports of Resistances and Therapeutic Innovations, UMR Inserm 1092, University of Limoges, 87000 Limoges, FrancePediatric Department, Mother and Child Biobank (CB-HME), Hôpital de la Mère et de l’enfant, CHU Limoges, 87000 Limoges, FranceSanofi Vaccines R&D, 69280 Marcy-l’étoile, FranceSanofi Vaccines R&D, 69280 Marcy-l’étoile, FranceBacteriology-Virology-Hygien Department, National Reference Center for Herpesviruses, Centre Hospitalier Universitaire de Limoges, 87000 Limoges, FranceHuman cytomegalovirus (HCMV) is the leading cause of congenital viral infection, leading to a variety of symptoms in the unborn child that range from asymptomatic to death in utero. Our objective was to better understand the mechanisms of placental infection by HCMV clinical strains, particularly during the first trimester of pregnancy. We thus characterized and compared the replication kinetics of various HCMV clinical strains and laboratory strains by measuring viral loads in an ex vivo model of first trimester villi and decidua, and used NGS and PCA analysis to analyze the genes involved in cell tropism and virulence factors. We observed that first trimester villi and decidua are similarly permissive to laboratory and symptomatic strains, and that asymptomatic strains poorly replicate in decidua tissue. PCA analysis allowed us to segregate our clinical strains based on their clinical characteristics, suggesting a link between gene mutations and symptoms. All these results bring forth elements that can help better understand the mechanisms that induce the appearance of symptoms or in the congenitally infected newborn.https://www.mdpi.com/2076-0817/12/8/985congenital cytomegalovirusclinical strainsplacentaviral kineticsmutations |
| spellingShingle | Deborah Andouard Valentin Tilloy Elodie Ribot Melissa Mayeras Daniel Diaz-Gonzalez Chahrazed El Hamel Fabienne Piras-Douce Nathalie Mantel Sophie Alain Genetic and Functional Characterization of Congenital HCMV Clinical Strains in Ex Vivo First Trimester Placental Model Pathogens congenital cytomegalovirus clinical strains placenta viral kinetics mutations |
| title | Genetic and Functional Characterization of Congenital HCMV Clinical Strains in Ex Vivo First Trimester Placental Model |
| title_full | Genetic and Functional Characterization of Congenital HCMV Clinical Strains in Ex Vivo First Trimester Placental Model |
| title_fullStr | Genetic and Functional Characterization of Congenital HCMV Clinical Strains in Ex Vivo First Trimester Placental Model |
| title_full_unstemmed | Genetic and Functional Characterization of Congenital HCMV Clinical Strains in Ex Vivo First Trimester Placental Model |
| title_short | Genetic and Functional Characterization of Congenital HCMV Clinical Strains in Ex Vivo First Trimester Placental Model |
| title_sort | genetic and functional characterization of congenital hcmv clinical strains in ex vivo first trimester placental model |
| topic | congenital cytomegalovirus clinical strains placenta viral kinetics mutations |
| url | https://www.mdpi.com/2076-0817/12/8/985 |
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