HHV-6A Infection of Endometrial Epithelial Cells Affects miRNA Expression and Trophoblast Cell Attachment

Reprod Sci. 2020 Mar;27(3):779-786. doi: 10.1007/s43032-019-00102-8. Epub 2020 Jan 1.

Abstract

We recently reported that human herpesvirus 6 (HHV-6) infection is frequently present in endometrial tissue of women with unexplained infertility, and that virus infection induces a profound remodulation of miRNA expression in human cells of different origin. Since specific miRNA patterns have been associated with specific pregnancy outcomes, we aimed to analyze the impact of HHV-6A infection on miRNAs expression and trophoblast receptivity in human endometrial cells. To this purpose, a human endometrial cell line (HEC-1A) was infected with HHV-6A and analyzed for alterations in the expression of miRNAs and for permissiveness to the attachment of a human choriocarcinoma trophoblast cell line (JEG-3). The results showed that HHV-6A infection of endometrial cells up-modulates miR22 (26-fold), miR15 (19.5-fold), and miR196-5p (12.1 fold), that are correlated with implant failure, and down-modulates miR18 (11.4 fold), miR101-3p (4.6 fold), miR181-5p (4.9 fold), miR92 (3.3 fold), and miR1207-5p (3.9 fold), characterized by a low expression in preeclampsia. Moreover, HHV-6A-infected endometrial cells infected resulted less permissive to the attachment of trophoblast cells. In conclusion, collected data suggest that HHV-6A infection could modify miRNA expression pattern and control of trophoblast cell adhesion of endometrial cells, undermining a correct trophoblast cell attachment on endometrial cells.

Keywords: Endometrium; HHV-6A; Infection; Pregnancy; miRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Adhesion*
  • Cell Line
  • Cell Line, Tumor
  • Choriocarcinoma / metabolism
  • Choriocarcinoma / virology
  • Endometrium / metabolism
  • Endometrium / virology*
  • Epithelial Cells / metabolism
  • Epithelial Cells / virology*
  • Female
  • Herpesvirus 6, Human / metabolism*
  • Humans
  • MicroRNAs / metabolism*
  • Roseolovirus Infections / metabolism*
  • Trophoblasts / metabolism
  • Trophoblasts / virology*
  • Uterine Neoplasms / metabolism
  • Uterine Neoplasms / virology

Substances

  • MicroRNAs