doi: 10.1038/srep35296.
ZIKA virus reveals broad tissue and cell tropism during the first trimester of pregnancy
Affiliations
- PMID:27759009
- PMCID: PMC5069472
- DOI: 10.1038/srep35296
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ZIKA virus reveals broad tissue and cell tropism during the first trimester of pregnancy
Hicham El Costa et al. Sci Rep..
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Abstract
The outbreak of the Zika Virus (ZIKV) and its association with fetal abnormalities have raised worldwide concern. However, the cellular tropism and the mechanisms of ZIKV transmission to the fetus during early pregnancy are still largely unknown. Therefore, we ex vivo modeled the ZIKV transmission at the maternal-fetal interface using organ culture from first trimester pregnancy samples. Here, we provide evidence that ZIKV strain circulating in Brazil infects and damages tissue architecture of the maternal decidua basalis, the fetal placenta and umbilical cord. We also show that ZIKV replicates differentially in a wide range of maternal and fetal cells, including decidual fibroblasts and macrophages, trophoblasts, Hofbauer cells as well as umbilical cord mesenchymal stem cells. The striking cellular tropism of ZIKV and its cytopathic-induced tissue injury during the first trimester of pregnancy could provide an explanation for the irreversible congenital damages.
Conflict of interest statement
The authors declare no competing financial interests.
Figures
(a) Decidua explants were infected with 6.1010 copies/mL of ZIKV. Viral titer was determined in culture supernatant by qRT-PCR. Data are represented as the mean of three biological replicates for each donor (n = 6). (b) Histopathological analysis of H&E-stained sections prepared from mock- and ZIKV-infected deciuda organ. Arrowhead point to ZIKV-induced cytopathic effect (top). Scale bar, 100 μm. Enlarged micrograph shows vacuolar cytoplasm and nuclear changes illustrated by karyorrhexis (bottom, arrowheads). Scale bar, 25 μm. (c) Kinetic of ZIKV replication in decidual fibroblasts (dFibroblasts) as determined by qRT-PCR (n = 6). (d) Representative large field view of mock- or ZIKV-infected dFibroblasts (ZIKV-env) at day 1 (d1) and day 3 (d3) post-infection. Bar graph represents the mean values determined from ten fields of view for each donor (n = 4). (e) 3D reconstitution of confocal microscopy of ZIKV-infected dFibroblasts at d3. Two representative profiles of ZIKV envelope staining. Scale bar, 20 μm. (f) Kinetic of ZIKV replication in decidual macrophages (dMacrophages) as determined by qRT-PCR (n = 6). (g) Representative large field view of mock- or ZIKV-infected dMacrophages (ZIKV-env) at day 3 (d3) and day 5 (d5) post-infection. Bar graph represents the mean values determined from ten fields of view for each donor. (n = 4). (h) 3D reconstitution of confocal microscopy of ZIKV-infected dMacrophages at d5. Scale bar, 20 μm. Primary cells were infected with ZIKV at a MOI of 1. Mean ± s.e.m. of n independent donors are represented. Friedman’s test with Dunn’s multiple comparison post-test was used. (*) represents statistical comparison between day 0 and other time points (#) represents statistical comparison between different time points. (*p < 0.05, ***p < 0.001,#p < 0.05).
(a) Placenta explants were infected with 6.1010 copies/mL of ZIKV. Viral titer was determined in culture supernatant by qRT-PCR. Data are represented as the mean of three biological replicates for each donor (n = 7). (b) Histopathological analysis of H&E-stained sections prepared from mock- and ZIKV-infected placental organ. Arrowhead point to gross alterations of tissue architecture with changes in trophoblast layers at the surface of the villi (Top). Scale bar, 100 μm. Enlarged micrograph shows nuclear changes illustrated by karyorrhexis and karyolysis (bottom, arrowheads). Scale bar, 25 μm. (c) Representative large field view of mock- or ZIKV-infected placental cells (ZIKV-env) at day 5 (d5) post-infection. Bar graph represents the mean values determined from ten fields of view for each donor (n = 4). (d) 3D reconstitution of confocal microscopy of ZIKV-infected mesenchymal/fibroblast-like cells (upper left micrograph), CTBs (lower left micrograph) and STBs (right micrograph) at d5. Scale bar, 20 μm. (e) Kinetic of ZIKV replication in Hofbauer cells as determined by qRT-PCR. (n = 6). (f) Representative large field view of mock- or ZIKV-infected Hofbauer cells (ZIKV-env) at day 5 (d5) post-infection. Bar graph represents the mean values determined from ten fields of view for each donor (n = 4). (g) 3D reconstitution of confocal microscopy of ZIKV-infected Hofbauer cells at d5. Scale bar, 20 μm. Primary cells were infected at a MOI of 1. Mean ± s.e.m. of n independent donors are represented. Friedman’s test with Dunn’s multiple comparison post-test was used. (*) represents statistical comparison between day 0 and other time points (*p < 0.05, ***p < 0.001).
(a) Umbilical cord (UC) rings were infected with 6.1010 copies/mL ZIKV and viral titer was determined in culture supernatant by qRT-PCR. Data are represented as the mean of three biological replicates for each donor (n = 7). (b) Relief phase contrast image of cell cluster and rapidly expanding adherent spindle-shaped fibroblast-like cells compatible with undifferentiated mesenchymal stem cells (MSC) morphology. Scale bar, 200 μm. (c) Representative flow cytometry histograms of UCMSC phenotype using CD31, CD45, CD90 and CD105 markers. Specific staining (blue) and control (red). (d) Kinetic of ZIKV replication in UCMSC as determined by qRT-PCR (n = 7). (e) Representative large field view of mock- or ZIKV-infected UCMSC (ZIKV-env) at day 5 (d5) post-infection. Bar graph represents the mean values determined from ten fields of view for each donor (n = 4). (f) 3D reconstitution of confocal microscopy of ZIKV-infected UCMSC at d5. Scale bar, 20 μm. (g) 3D reconstitution of confocal microscopy of ZIKV-infected UCMSC-organized cluster at d5. Scale bar, 200 μm. Primary cells were infected with ZIKV at a MOI of 1. Mean ± s.e.m. of n independent donors are represented. Friedman’s test with Dunn’s multiple comparison post-test was used. (*) represents statistical comparison between day 0 and other time points (*p < 0.05, **p < 0.01, ***p < 0.001).
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