Human placental trophoblasts confer viral resistance to recipient cells

被引:383
作者
Delorme-Axford, Elizabeth [1 ]
Donker, Rogier B. [2 ]
Mouillet, Jean-Francois [2 ]
Chu, Tianjiao [2 ]
Bayer, Avraham [2 ]
Ouyang, Yingshi [2 ]
Wang, Tianyi [3 ]
Stolz, Donna B. [4 ]
Sarkar, Saumendra N. [1 ,5 ]
Morelli, Adrian E. [6 ]
Sadovsky, Yoel [1 ,2 ]
Coyne, Carolyn B. [1 ]
机构
[1] Univ Pittsburgh, Dept Microbiol & Mol Genet, Pittsburgh, PA 15219 USA
[2] Univ Pittsburgh, Dept Obstet Gynecol & Reprod Sci, Magee Womens Res Inst, Pittsburgh, PA 15213 USA
[3] Univ Pittsburgh, Dept Infect Dis & Microbiol, Pittsburgh, PA 15261 USA
[4] Univ Pittsburgh, Dept Cell Biol & Physiol, Pittsburgh, PA 15261 USA
[5] Univ Pittsburgh, Inst Canc, Canc Virol Program, Pittsburgh, PA 15213 USA
[6] Univ Pittsburgh, Dept Surg, Pittsburgh, PA 15213 USA
基金
美国国家卫生研究院;
关键词
C19MC; primary human trophoblasts; miR-517-3p; HUMAN CYTOMEGALOVIRUS; DENDRITIC CELLS; MATERNAL PLASMA; VACCINIA VIRUS; MESSENGER-RNA; MICRORNAS; AUTOPHAGY; EXOSOMES; EXPRESSION; MECHANISM;
D O I
10.1073/pnas.1304718110
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:12048 / 12053
页数:6
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