Human Cytomegalovirus Modifies Placental Small Extracellular Vesicle Composition to Enhance Infection of Fetal Neural Cells In Vitro

Viruses. 2022 Sep 13;14(9):2030. doi: 10.3390/v14092030.


Although placental small extracellular vesicles (sEVs) are extensively studied in the context of pregnancy, little is known about their role during viral congenital infection, especially at the beginning of pregnancy. In this study, we examined the consequences of human cytomegalovirus (hCMV) infection on sEVs production, composition, and function using an immortalized human cytotrophoblast cell line derived from first trimester placenta. By combining complementary approaches of biochemistry, electron microscopy, and quantitative proteomic analysis, we showed that hCMV infection increases the yield of sEVs produced by cytotrophoblasts and modifies their protein content towards a potential proviral phenotype. We further demonstrate that sEVs secreted by hCMV-infected cytotrophoblasts potentiate infection in naive recipient cells of fetal origin, including human neural stem cells. Importantly, these functional consequences are also observed with sEVs prepared from an ex vivo model of infected histocultures from early placenta. Based on these findings, we propose that placental sEVs could be important actors favoring viral dissemination to the fetal brain during hCMV congenital infection.

Keywords: congenital infection; cytotrophoblast; extracellular vesicles; hCMV; placenta.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cytomegalovirus / genetics
  • Cytomegalovirus Infections*
  • Extracellular Vesicles* / metabolism
  • Female
  • Humans
  • Placenta
  • Pregnancy
  • Proteomics

Grant support

This project has received financial support from the French Biomedicine Agency, and institutional grants from Inserm, CNRS, and Toulouse 3 University. This project is part of the doctorate thesis of Mathilde Bergamelli, who was funded by the Ministry of Education and Research (MESR). The TEM experiments were performed on PICT-IBiSA, Institut Curie, Paris, member of the France-BioImaging national research infrastructure, and were supported by the French National Research Agency through the “Investments for the Future” program (France-BioImaging, ANR-11-INSB-04), supported by the CelTisPhyBio Labex (N° ANR-11-LB0038) part of the IDEX PSL (N°ANR-10-IDEX-0001-02 PSL). The proteomic part of this project was supported in part by the Région Occitanie, European funds (Fonds Européens de Développement Régional, FEDER), Toulouse Métropole, and by the French Ministry of Research with the Investissement d’Avenir Infrastructures Nationales en Biologie et Santé program (ProFI, Proteomics French Infrastructure project, ANR-10-INBS-08).