| Title: |
Impact of congenital infection by human Cytomegalovirus on placental small extracellular vesicles secretion and consequences on fetal brain development ; Impact de l'infection congénitale par le Cytomégalovirus humain sur la sécrétion de petites vésicules extracellulaires placentaires et conséquences sur le développement cérébral fœtal |
| Authors: |
Bergamelli, Mathilde |
| Contributors: |
Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity); Université Toulouse III - Paul Sabatier (UT3); Communauté d'universités et établissements de Toulouse (Comue de Toulouse)-Communauté d'universités et établissements de Toulouse (Comue de Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS); Université Paul Sabatier - Toulouse III; Cécile Malnou |
| Source: |
https://theses.hal.science/tel-03651481 ; Virologie. Université Paul Sabatier - Toulouse III, 2021. Français. ⟨NNT : 2021TOU30179⟩. |
| Publisher Information: |
CCSD |
| Publication Year: |
2021 |
| Collection: |
Université Toulouse III - Paul Sabatier: HAL-UPS |
| Subject Terms: |
Congenital infection; Human Cytomegalovirus; Small extra-cellular vesicles; Placenta; Cytomégalovirus humain; Infection congénitale; Petites vésicules extracellulaires; [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology; [SDV.MHEP.GEO]Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics |
| Description: |
Congenital infection by human Cytomegalovirus (hCMV) is a major public health issue. In so-called developed countries, it is the leading cause of neonatal neurosensory defects of infectious origin. Infection by hCMV induces placental and fetal brain lesions of variable intensity. The pathophysiological mechanisms leading to fetal damage, however, remain poorly understood. In addition, the medical monitoring of this pregnancy infection is complicated by the lack of non-invasive diagnostic and prognostic tools. The production of certain mediators by the infected placenta could partly explain the type of fetal damages. Among these mediators, the placental small Extracellular Vesicles (sEV) transmit biological information both in maternal and fetal compartments. These lipid nanovesicles, loaded with proteins and miRNA, are therefore of particular interest in the context of congenital hCMV infection, because they could 1 / play a role in the transmission of biological information from the infected placenta to the fetus and 2 / allow, via their presence in the maternal plasma, the development of biomarkers monitoring hCMV positive pregnancies. During my thesis, I sought to evaluate these two hypotheses, by combining trophoblastic cell models, ex vivo placental explants and in vivo clinical samples. First, my results showed that infection by hCMV modifies the secretion and composition of trophoblastic sEVs, which express a protein profile theoretically facilitating infection. Subsequently, I showed that these trophoblastic sEVs modified by hCMV exert a proviral effect on fetal cells naive of any infection (fibroblasts and neural stem cells). This proviral effect on the rate of infection of naive neural stem cells is also found with sEV from early placenta infected ex vivo and with sEV from amniotic fluid from pregnant patients with hCMV seroconversion. In addition, I developed a biobank composed of different samples from patients experiencing hCMV seroconversion during pregnancy. The two objectives of this biobank are ... |
| Document Type: |
doctoral or postdoctoral thesis |
| Language: |
French |
| Relation: |
NNT: 2021TOU30179 |
| Availability: |
https://theses.hal.science/tel-03651481; https://theses.hal.science/tel-03651481v1/document; https://theses.hal.science/tel-03651481v1/file/2021TOU30179a.pdf |
| Rights: |
https://about.hal.science/hal-authorisation-v1/ ; info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.298FA09A |
| Database: |
BASE |