Human trophoblasts confer resistance to viruses implicated in perinatal infection

被引:84
作者
Bayer, Avraham [1 ]
Delorme-Axford, Elizabeth [4 ]
Sleigher, Christie [6 ]
Frey, Teryl K. [6 ]
Trobaugh, Derek W. [2 ]
Klimstra, William B. [2 ]
Emert-Sedlak, Lori A. [4 ]
Smithgall, Thomas E. [3 ,4 ]
Kinchington, Paul R. [4 ,5 ]
Vadia, Stephen [7 ,8 ]
Seveau, Stephanie [7 ,8 ]
Boyle, Jon P. [9 ]
Coyne, Carolyn B. [4 ]
Sadovsky, Yoel [1 ,4 ]
机构
[1] Univ Pittsburgh, Dept Obstet Gynecol & Reprod Sci, Magee Womens Res Inst, Sch Med, Pittsburgh, PA 15260 USA
[2] Univ Pittsburgh, Sch Med, Ctr Vaccine Res, Pittsburgh, PA USA
[3] Univ Pittsburgh, Sch Med, Drug Discovery Inst, Pittsburgh, PA USA
[4] Univ Pittsburgh, Dept Microbiol & Mol Genet, Sch Med, Pittsburgh, PA USA
[5] Univ Pittsburgh, Dept Ophthalmol, Sch Med, Pittsburgh, PA 15260 USA
[6] Georgia State Univ, Dept Biol, Atlanta, GA USA
[7] Ohio State Univ, Ctr Microbial Interface Biol, Columbus, OH 43210 USA
[8] Ohio State Univ, Dept Microbial Infect & Immun, Columbus, OH 43210 USA
[9] Univ Pittsburgh, Dept Biol Sci, Dietrich Sch Arts & Sci, Pittsburgh, PA 15260 USA
基金
美国国家卫生研究院;
关键词
chromosome 19 microRNA cluster; conditioned medium; microRNA; trophoblasts; viruses; LISTERIA-MONOCYTOGENES; C19MC MICRORNAS; PREGNANCY; EXPRESSION; VARICELLA; ZOSTER; TYPE-1; DIFFERENTIATION; TRANSMISSION; PLACENTA;
D O I
10.1016/j.ajog.2014.07.060
中图分类号
R71 [妇产科学];
学科分类号
100211 ;
摘要
OBJECTIVE: Primary human trophoblasts were previously shown to be resistant to viral infection, and able to confer this resistance to non-trophoblast cells. Can trophoblasts protect nontrophoblastic cells from infection by viruses or other intracellular pathogens that are implicated in perinatal infection? STUDY DESIGN: Isolated primary term human trophoblasts were cultured for 48-72 hours. Diverse nonplacental human cell lines (U2OS, human foreskin fibroblast, TZM-bl, MeWo, and Caco-2) were preexposed to either trophoblast conditioned medium, nonconditioned medium, or miR-517-3p for 24 hours. Cells were infected with several viral and nonviral pathogens known to be associated with perinatal infections. Cellular infection was defined and quantified by plaque assays, luciferase assays, microscopy, and/ or colonization assays. Differences in infection were assessed by Student t test or analysis of variance with Bonferroni correction. RESULTS: Infection by rubella and other togaviruses, human immunodeficiency virus-1, and varicella zoster was attenuated in cells preexposed to trophoblast-conditioned medium (P < .05), and a partial effect by the chromosome 19 microRNA miR-517-3p on specific pathogens. The conditioned medium had no effect on infection by Toxoplasma gondii or Listeria monocytogenes. CONCLUSION: Our findings indicate that medium conditioned by primary human trophoblasts attenuates viral infection in nontrophoblastic cells. Our data point to a trophoblast-specific antiviral effect that may be exploited therapeutically.
引用
收藏
页码:71.e1 / 71.e8
页数:8
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