Human placental trophoblasts confer viral resistance to recipient cells

Elizabeth Delorme‐Axford(University of Pittsburgh), Rogier B. Donker(University of Pittsburgh), Jean‐François Mouillet(University of Pittsburgh), Tianjiao Chu(University of Pittsburgh), Avraham Bayer(University of Pittsburgh), Yingshi Ouyang(University of Pittsburgh), Tianyi Wang(New York University), Donna B. Stolz(University of Pittsburgh), Saumendra N. Sarkar(University of Pittsburgh), Adrián E. Morelli(University of Pittsburgh), Yoel Sadovsky(University of Pittsburgh), Carolyn B. Coyne(University of Pittsburgh)
Proceedings of the National Academy of Sciences
July 1, 2013
Cited by 493Open Access
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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.


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