Human placental trophoblasts confer viral resistance to recipient cells
Elizabeth Delorme-Axford, Rogier B Donker, Jean-Francois Mouillet, Tianjiao Chu, Avraham Bayer, Yingshi Ouyang, Tianyi Wang, Donna B Stolz, Saumendra N Sarkar, Adrian E Morelli, Yoel Sadovsky, Carolyn B Coyne, Elizabeth Delorme-Axford, Rogier B Donker, Jean-Francois Mouillet, Tianjiao Chu, Avraham Bayer, Yingshi Ouyang, Tianyi Wang, Donna B Stolz, Saumendra N Sarkar, Adrian E Morelli, Yoel Sadovsky, Carolyn B Coyne
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.
Conflict of interest statement
Conflict of interest statement: C.B.C. and Y.S. are named inventors on a pending patent application describing the use of C19MC microRNAs as therapeutics.
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Source: PubMed