Human placental trophoblasts confer viral resistance to recipient cells

Proc Natl Acad Sci U S A. 2013 Jul 16;110(29):12048-53. doi: 10.1073/pnas.1304718110. Epub 2013 Jul 1.

Abstract

Placental trophoblasts form the interface between the fetal and maternal environments and serve to limit the maternal-fetal spread of viruses. Here we show that cultured primary human placental trophoblasts are highly resistant to infection by a number of viruses and, importantly, confer this resistance to nonplacental recipient cells by exosome-mediated delivery of specific microRNAs (miRNAs). We show that miRNA members of the chromosome 19 miRNA cluster, which are almost exclusively expressed in the human placenta, are packaged within trophoblast-derived exosomes and attenuate viral replication in recipient cells by the induction of autophagy. Together, our findings identify an unprecedented paracrine and/or systemic function of placental trophoblasts that uses exosome-mediated transfer of a unique set of placental-specific effector miRNAs to directly communicate with placental or maternal target cells and regulate their immunity to viral infections.

Keywords: C19MC; miR-517-3p; primary human trophoblasts.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Autophagy / genetics*
  • Cells, Cultured
  • Chromosomes, Human, Pair 19 / genetics*
  • Disease Resistance / genetics*
  • Enzyme-Linked Immunosorbent Assay
  • Exosomes / genetics
  • Exosomes / metabolism
  • Female
  • Green Fluorescent Proteins
  • Humans
  • MicroRNAs / genetics*
  • Placenta / cytology*
  • Placenta / metabolism
  • Pregnancy
  • Trophoblasts / metabolism
  • Trophoblasts / virology*
  • Virus Diseases / transmission*

Substances

  • MIRN517 microRNA, human
  • MicroRNAs
  • Green Fluorescent Proteins