Zika virus causes placental pyroptosis and associated adverse fetal outcomes by activating GSDME
- State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, China
- Key Laboratory of Preventive Veterinary Medicine in Hubei Province, College of Veterinary Medicine, Huazhong Agricultural University, China
- The Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural University, China
- College of Veterinary Medicine, Huazhong Agricultural University, China
Figures
Figure 1 with 1 supplement
Zika virus (ZIKV) infection induces the gasdermin E (GSDME)-mediated pyroptosis in JEG-3 cells.
JEG-3 or GSDME-KO JEG-3 cells were infected with ZIKV at a multiplicity of infection (MOI) of 1. At indicated time post-infection, cells were subjected to microscopy, cytotoxicity, and Western blot …
-
Figure 1—source data 1
Raw data for Figure 1.
- https://cdn.elifesciences.org/articles/73792/elife-73792-fig1-data1-v1.zip
Figure 1—figure supplement 1
Gasdermin E (GSDME) does not affect Zika virus (ZIKV) replication in JEG-3 cells.
Negative control (NC), GSDME KO, GSDME-overexpressed and GFP-overexpressed JEG-3 cells were infected with ZIKV at a multiplicity of infection (MOI) of 0.1. The supernatants of ZIKV-infected cells …
-
Figure 1—figure supplement 1—source data 1
Raw data for Figure 1—figure supplement 1.
- https://cdn.elifesciences.org/articles/73792/elife-73792-fig1-figsupp1-data1-v1.xlsx
Figure 2 with 1 supplement
Both the cellular gasdermin E (GSDME) abundance and the susceptibility to Zika virus (ZIKV) infection determine the occurrence of pyroptosis.
(A–C) Relevant cells were infected with ZIKV at a multiplicity of infection (MOI) of 1. At indicated time post-infection, cells were subjected to microscopy, cytotoxicity, and Western blot analyses. …
-
Figure 2—source data 1
Raw data for Figure 2.
- https://cdn.elifesciences.org/articles/73792/elife-73792-fig2-data1-v1.zip
Figure 2—figure supplement 1
The gasdermin E (GSDME) abundance and the susceptibility to Zika virus (ZIKV) infection of different cell lines.
(A) Immunoblot analyses of GSDME-FL in indicated cell lines. (B–C) Relevant cells were infected with ZIKV at a multiplicity of infection (MOI) of 0.1. At indicated time post-infection, cells were …
-
Figure 2—figure supplement 1—source data 1
Raw data for Figure 2—figure supplement 1.
- https://cdn.elifesciences.org/articles/73792/elife-73792-fig2-figsupp1-data1-v1.zip
Figure 3 with 1 supplement
Zika virus (ZIKV) infection activates gasdermin E (GSDME) via extrinsic apoptotic pathway.
(A–C) JEG-3 cells were infected with ZIKV at a multiplicity of infection (MOI) of 1 followed by incubated with either 10 μM VX-765, 25 μM Z-DEVD-FMK, 25 μM Z-VAD-FMK, or 10 μM GSK872. At 24 hr …
-
Figure 3—source data 1
Raw data for Figure 3.
- https://cdn.elifesciences.org/articles/73792/elife-73792-fig3-data1-v1.zip
Figure 3—figure supplement 1
Zika virus (ZIKV) infection activates caspase-3 and caspase-8 in JEG-3 cells.
(A) Immunoblot analyses of GSDME-FL, GSDME-N, and casepase-3 in ZIKV-infected JEG-3 cells. (B) The grayscale analysis of Figure 3C. (C) Immunoblot analyses of GSDME-FL, GSDME-N, caspase-9, and …
-
Figure 3—figure supplement 1—source data 1
Raw data for Figure 3—figure supplement 1.
- https://cdn.elifesciences.org/articles/73792/elife-73792-fig3-figsupp1-data1-v1.zip
Figure 4 with 2 supplements
The genomic RNA of Zika virus (ZIKV) activates the gasdermin E (GSDME)-dependent pyroptosis through the RIG-I-caspase-8-caspase-3 pathway.
(A–C) JEG-3 cells were seeded in six-well plates and were transfected with 1 μg ZIKV 5’ untranslated region (UTR) or 3’ UTR. At 24 hr post-transfection, cells were subjected to microscopy (A), …
-
Figure 4—source data 1
Raw data for Figure 4.
- https://cdn.elifesciences.org/articles/73792/elife-73792-fig4-data1-v1.zip
Figure 4—figure supplement 1
The structural and non-structural proteins of Zika virus (ZIKV) are not capable of inducing pyroptosis in JEG-3 cells.
(A–B) JEG-3 cells were infected with ZIKV or UV-inactivated ZIKV at a multiplicity of infection (MOI) of 1. At 24 hr post-infection, the cleavage of gasdermin E (GSDME) (A), LDH release, and cell …
-
Figure 4—figure supplement 1—source data 1
Raw data for Figure 4—figure supplement 1.
- https://cdn.elifesciences.org/articles/73792/elife-73792-fig4-figsupp1-data1-v1.zip
Figure 4—figure supplement 2
Activation of RIG-I is sufficient to induce gasdermin E (GSDME)-dependent pyroptosis.
(A) Verification of RIG-I, TLR7, and TLR8 knockdown efficiency by immunoblotting. (B–C) JEG-3 cells were seeded in six-well plate and transfected with 7.5 μl Lipofectamine 2000 Transfection Reagent, …
-
Figure 4—figure supplement 2—source data 1
Raw data for Figure 4—figure supplement 2.
- https://cdn.elifesciences.org/articles/73792/elife-73792-fig4-figsupp2-data1-v1.zip
Figure 5 with 2 supplements
Zika virus (ZIKV) infection of pregnant immunocompetent wild-type (WT) C57BL/6N mice results in gasdermin E (GSDME)-mediated placental pyroptosis and congenital ZIKV syndrome (CZS).
(A) Scheme of infection and the follow-up analyses. The WT or Gsdme-/- female mice were mated with male mice of their respective genotypes, and the pregnant mice were infected intravenously with …
-
Figure 5—source data 1
Raw data for Figure 5.
- https://cdn.elifesciences.org/articles/73792/elife-73792-fig5-data1-v1.zip
Figure 5—figure supplement 1
Zika virus (ZIKV) infection induces the gasdermin E (GSDME)-mediated pyroptosis in mouse primary trophoblast cells (MTCs).
(A) Primary MTCs were isolated from mouse placentas, and incubated at 37°C in a 5% CO2 incubator. After 72 hr, immunofluorescence analysis was conducted by using antibody against …
-
Figure 5—figure supplement 1—source data 1
Raw data for Figure 5—figure supplement 1.
- https://cdn.elifesciences.org/articles/73792/elife-73792-fig5-figsupp1-data1-v1.zip
Figure 5—figure supplement 2
Gasdermin E (GSDME) deletion alleviates Zika virus (ZIKV)-induced abnormal pregnancy and adverse fetal outcomes.
Pregnant wild-type (WT) and Gsdme-/- dams were infected with ZIKV or Vero cell culture supernatant (Mock) as described in Figure 5A. (A) Measurements of daily weight of dams after ZIKV infection are …
-
Figure 5—figure supplement 2—source data 1
Raw data for Figure 5—figure supplement 2.
- https://cdn.elifesciences.org/articles/73792/elife-73792-fig5-figsupp2-data1-v1.zip
Figure 6 with 1 supplement
Induction of TNF-α expression contributes to placental damage in Zika virus (ZIKV)-infected pregnant mice.
(A–B) The pregnant C57BL/6N mice were mock-infected or intravenously infected with 1×106 PFU of ZIKV H/PF/2013 strain at embryonic day 9.5 (E9.5). At E16.5, placentas were collected and the mRNA …
-
Figure 6—source data 1
Raw data for Figure 6.
- https://cdn.elifesciences.org/articles/73792/elife-73792-fig6-data1-v1.zip
Figure 6—figure supplement 1
R-7050 treatment attenuates Zika virus (ZIKV)-induced adverse fetal outcomes.
The weight of fetuses from mock- and ZIKV-infected dams treated with R-7050 or vehicle at E16.5 (vehicle, n=41; vehicle + ZIKV, n=39; R-7050 + ZIKV, n=47). Data shown are median with interquartile …
-
Figure 6—figure supplement 1—source data 1
Raw data for Figure 6—figure supplement 1.
- https://cdn.elifesciences.org/articles/73792/elife-73792-fig6-figsupp1-data1-v1.xlsx
