Abstract
Zika virus (ZIKV) infection at the maternal–placental interface is associated with adverse pregnancy outcomes including fetal demise and pregnancy loss. To determine how infection impacts placental trophoblasts, we utilized rhesus macaque trophoblast stem cells (TSC) that can be differentiated into early gestation syncytiotrophoblasts (ST) and extravillous trophoblasts (EVT). TSCs and STs, but not EVTs, were highly permissive to productive infection with ZIKV strain DAK AR 41524. The impact of ZIKV on the cellular transcriptome showed that infection of TSCs and STs increased expression of immune related genes, including those involved in type I and type III interferon responses. ZIKV exposure altered extracellular vesicle (EV) mRNA, miRNA and protein cargo, including ZIKV proteins, regardless of productive infection. These findings suggest that early gestation macaque TSCs and STs are permissive to ZIKV infection, and that EV analysis may provide a foundation for identifying non-invasive biomarkers of placental infection in a highly translational model.
| Original language | English (US) |
|---|---|
| Article number | 7348 |
| Journal | Scientific reports |
| Volume | 12 |
| Issue number | 1 |
| DOIs | |
| State | Published - Dec 2022 |
Funding
Thank you to Dr. Shelby O’Connor and John James Baczenas in the Department of Pathology and Laboratory Medicine at the University of Wisconsin-Madison for sequencing the ZIKV stock used in this study. We would also like to thank Drs. Greg Barrett-Wilt and Greg Sabat at the University of Wisconsin-Madison Biotechnology Center for processing and analyzing the mass spectroscopy samples. We also thank Dr. Mark Berres at the University of Wisconsin-Madison Biotechnology Center for processing and analyzing the miRNAseq data. Thanks to Dr. Randall Massey at the University of Wisconsin-Madison Electron Microscope Core for taking the transmission electron microscope images. We would like to acknowledge Drs. Kristen Bernard and Margaret Petroff for their guidance in viral stock propagation and EV isolation, respectively. This research was funded by NIH grants F31 HD100057 to L.N.B., K99 HD099154 to J.K.S., NIH T32 GM007133 to M.C.M., R21 HD091163 and R01 AI 132519 to T.G.G, and P51 OD011106-54 to the Wisconsin National Primate Research Center. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. Thank you to Dr. Shelby O?Connor and John James Baczenas in the Department of Pathology and Laboratory Medicine at the University of Wisconsin-Madison for sequencing the ZIKV stock used in this study. We would also like to thank Drs. Greg Barrett-Wilt and Greg Sabat at the University of Wisconsin-Madison Biotechnology Center for processing and analyzing the mass spectroscopy samples. We also thank Dr. Mark Berres at the University of Wisconsin-Madison Biotechnology Center for processing and analyzing the miRNAseq data. Thanks to Dr. Randall Massey at the University of Wisconsin-Madison Electron Microscope Core for taking the transmission electron microscope images. We would like to acknowledge Drs. Kristen Bernard and Margaret Petroff for their guidance in viral stock propagation and EV isolation, respectively. This research was funded by NIH grants F31 HD100057 to L.N.B., K99 HD099154 to J.K.S., NIH T32 GM007133 to M.C.M., R21 HD091163 and R01 AI 132519 to T.G.G, and P51 OD011106-54 to the Wisconsin National Primate Research Center. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.
ASJC Scopus subject areas
- General
