Ex vivo model of congenital cytomegalovirus infection and new combination therapies

التفاصيل البيبلوغرافية
العنوان: Ex vivo model of congenital cytomegalovirus infection and new combination therapies
المؤلفون: D. Andouard, William D. Rawlinson, Y. Aubard, Sébastien Hantz, Claude-Alain Calliste, Marie-Cécile Ploy, Sophie Alain, L. Morère, F. Esclaire, F. Labrousse, Sébastien Cotin, F. Saade
المساهمون: Anti-infectieux : supports moléculaires des résistances et innovations thérapeutiques (RESINFIT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-CHU Limoges, Service de Bactériologie, Virologie, Hygiène [CHU Limoges], CHU Limoges, Service d'Hématologie biologique [CHU Limoges], Laboratoire de Chimie des Substances Naturelles (LCSN), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503), Service de Gynécologie-Obstétrique [CHU Limoges], Virology Division, SEALS Microbiology and SOMS, BABS UNSW, Service d'Histologie, cytologie, cytogénétique, biologie cellulaire [CHU Limoges]
المصدر: Placenta
Placenta, Elsevier, 2015, 36 (1), pp.41-47. ⟨10.1016/j.placenta.2014.11.003⟩
بيانات النشر: Elsevier BV, 2015.
سنة النشر: 2015
مصطلحات موضوعية: Adult, Human cytomegalovirus, Artesunate, [SDV.MHEP.GEO]Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, Antiviral Agents, Rubella, chemistry.chemical_compound, Placental infection, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Pregnancy, Placenta, medicine, Humans, Pregnancy Complications, Infectious, Fetus, biology, Parvovirus, Obstetrics and Gynecology, Maribavir, medicine.disease, biology.organism_classification, Virology, Artemisinins, Trophoblasts, 3. Good health, medicine.anatomical_structure, Reproductive Medicine, chemistry, Cytomegalovirus Infections, Flavanones, Immunology, Benzimidazoles, Female, Ribonucleosides, Flavonoïds, Ex vivo model, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Ex vivo, Developmental Biology
الوصف: Introduction Congenital human cytomegalovirus (HCMV) infection is a major public health problem due to severe sequelae in the fetus and newborns. Currently, due to their toxicity anti-CMV treatments cannot be administered to pregnant women. We thus developed an ex vivo model of 1st trimester placental CMV infection to observe the route of infection across the placenta and to test the efficacy of various new drugs targeting different stages of viral cycle. Methods After validation of the viability of floating villi explants by ELISA β-HCG, the kinetics of placental infection were determined by immunochemistry and qPCR in this ex vivo model. Antiviral susceptibility was determined in vitro using focus reduction assay and by qPCR in the ex vivo model. Results The ex vivo model showed viral infection in trophoblasts and mesenchymal space of floating villi. In vitro, antiviral combinations of maribavir with baicalein or artesunate inhibited viral infection by more than 90%. On the other hand, in ex vivo model, infection was reduced by 40% in presence of maribavir and artesunate. The synergistic effect observed in vitro was not observed ex vivo. Discussion This model allowed us to understand the CMV spread in 1st trimester floating villi better and to analyze the anti-CMV efficacy and toxicity of new drugs that could be administered to pregnant women, either alone or in combination. Conclusions Such an ex vivo model could be applied to other viruses such as rubella or parvovirus B19 and in new drug development.
تدمد: 0143-4004
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::621536515a825e1a5defdbee035f317a
https://doi.org/10.1016/j.placenta.2014.11.003
حقوق: CLOSED
رقم الأكسشن: edsair.doi.dedup.....621536515a825e1a5defdbee035f317a
قاعدة البيانات: OpenAIRE