Chromosome 19 microRNAs exert antiviral activity independent from type III interferon signaling.

dc.contributor.author

Bayer, Avraham

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Lennemann, Nicholas J

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Ouyang, Yingshi

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Sadovsky, Elena

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Sheridan, Megan A

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Roberts, R Michael

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Coyne, Carolyn B

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Sadovsky, Yoel

dc.date.accessioned

2021-04-16T19:59:26Z

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2021-04-16T19:59:26Z

dc.date.issued

2018-01

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2021-04-16T19:59:21Z

dc.description.abstract

INTRODUCTION:Cultured primary human trophoblasts (PHT), derived from term placentas, are relatively resistant to infection by diverse viruses. The resistance can be conferred to non-trophoblastic cells by pre-exposing them to medium that was conditioned by PHT cells. This antiviral effect is mediated, at least in part, by microRNAs (miRNA) expressed from the chromosome 19 microRNA cluster (C19MC). Recently we showed that PHT cells and cells pre-exposed to PHT medium are also resistant to infection by Zika virus (ZIKV), an effect mediated by the constitutive release of the type III interferons (IFN) IFN lambda-1 and IFN lambda-2 in trophoblastic medium. We hypothesized that trophoblastic C19MC miRNA are active against ZIKV, and assessed the interaction of this pathway with IFN lambda-1 - mediated resistance. METHODS:Term PHT cells were cultured using standard techniques. An osteosarcoma cell line (U2OS) was used as non-trophoblastic cells, which were infected with either ZIKV or vesicular stomatitis virus (VSV). Trophoblastic extracellular vesicles (EVs) were produced by gradient ultracentrifugation. RT-qPCR was used to determine viral infection, cellular or medium miRNA levels and the expression of interferon-stimulated genes. RESULTS:We showed that C19MC miRNA attenuate infection of U2OS cells by ZIKV, and that C19MC miRNA or exosomes that contain C19MC miRNA did not influence the type III IFN pathway. Similarly, cell exposure to recombinant IFN lambda-1 had no effect on miRNA expression, and these pathways did not exhibit synergistic interaction. DISCUSSION:PHT cells exert antiviral activity by at least two independent mechanisms, mediated by C19MC miRNA and by type III IFNs.

dc.identifier

S0143-4004(17)31174-8

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0143-4004

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1532-3102

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https://hdl.handle.net/10161/22587

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eng

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Elsevier BV

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Placenta

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10.1016/j.placenta.2017.11.004

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Cells, Cultured

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Cell Line, Tumor

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Chromosomes, Human, Pair 19

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Trophoblasts

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Placenta

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Humans

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Interferons

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Protein Isoforms

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Recombinant Proteins

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MicroRNAs

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Culture Media, Conditioned

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Cell Differentiation

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Immunity

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Pregnancy

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Multigene Family

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Adult

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Female

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Exosomes

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Induced Pluripotent Stem Cells

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Extracellular Vesicles

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Zika Virus

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Zika Virus Infection

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Chromosome 19 microRNAs exert antiviral activity independent from type III interferon signaling.

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Journal article

duke.contributor.orcid

Coyne, Carolyn B|0000-0002-1884-6309

pubs.begin-page

33

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38

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School of Medicine

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Molecular Genetics and Microbiology

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Duke

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Basic Science Departments

pubs.publication-status

Published

pubs.volume

61

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