Vertical transmission of African-lineage Zika virus through the fetal membranes in a rhesus macaque (Macaca mulatta) model.
Zika virus (ZIKV) can be transmitted vertically from mother to fetus during pregnancy, resulting in a range of outcomes including severe birth defects and fetal/infant death. Potential pathways of vertical transmission in utero have been proposed but remain undefined. Identifying the timing and rout...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2023-08-01
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| Series: | PLoS Pathogens |
| Online Access: | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1011274&type=printable |
| _version_ | 1827104389123276800 |
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| author | Michelle R Koenig Ann M Mitzey Xiankun Zeng Leticia Reyes Heather A Simmons Terry K Morgan Ellie K Bohm Julia C Pritchard Jenna A Schmidt Emily Ren Fernanda B Leyva Jaimes Eva Winston Puja Basu Andrea M Weiler Thomas C Friedrich Matthew T Aliota Emma L Mohr Thaddeus G Golos |
| author_facet | Michelle R Koenig Ann M Mitzey Xiankun Zeng Leticia Reyes Heather A Simmons Terry K Morgan Ellie K Bohm Julia C Pritchard Jenna A Schmidt Emily Ren Fernanda B Leyva Jaimes Eva Winston Puja Basu Andrea M Weiler Thomas C Friedrich Matthew T Aliota Emma L Mohr Thaddeus G Golos |
| author_sort | Michelle R Koenig |
| collection | DOAJ |
| description | Zika virus (ZIKV) can be transmitted vertically from mother to fetus during pregnancy, resulting in a range of outcomes including severe birth defects and fetal/infant death. Potential pathways of vertical transmission in utero have been proposed but remain undefined. Identifying the timing and routes of vertical transmission of ZIKV may help us identify when interventions would be most effective. Furthermore, understanding what barriers ZIKV overcomes to effect vertical transmission may help improve models for evaluating infection by other pathogens during pregnancy. To determine the pathways of vertical transmission, we inoculated 12 pregnant rhesus macaques with an African-lineage ZIKV at gestational day 30 (term is 165 days). Eight pregnancies were surgically terminated at either seven or 14 days post-maternal infection. Maternal-fetal interface and fetal tissues and fluids were collected and evaluated for ZIKV using RT-qPCR, in situ hybridization, immunohistochemistry, and plaque assays. Four additional pregnant macaques were inoculated and terminally perfused with 4% paraformaldehyde at three, six, nine, or ten days post-maternal inoculation. For these four cases, the entire fixed pregnant uterus was evaluated with in situ hybridization for ZIKV RNA. We determined that ZIKV can reach the MFI by six days after infection and infect the fetus by ten days. Infection of the chorionic membrane and the extraembryonic coelomic fluid preceded infection of the fetus and the mesenchymal tissue of the placental villi. We did not find evidence to support a transplacental route of ZIKV vertical transmission via infection of syncytiotrophoblasts or villous cytotrophoblasts. The pattern of infection observed in the maternal-fetal interface provides evidence of paraplacental vertical ZIKV transmission through the chorionic membrane, the outer layer of the fetal membranes. |
| first_indexed | 2024-04-24T07:57:40Z |
| format | Article |
| id | doaj.art-e28b7219fce54b63b1bf6e6e718f3ad3 |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2025-03-20T09:22:09Z |
| publishDate | 2023-08-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj.art-e28b7219fce54b63b1bf6e6e718f3ad32024-09-26T05:31:43ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742023-08-01198e101127410.1371/journal.ppat.1011274Vertical transmission of African-lineage Zika virus through the fetal membranes in a rhesus macaque (Macaca mulatta) model.Michelle R KoenigAnn M MitzeyXiankun ZengLeticia ReyesHeather A SimmonsTerry K MorganEllie K BohmJulia C PritchardJenna A SchmidtEmily RenFernanda B Leyva JaimesEva WinstonPuja BasuAndrea M WeilerThomas C FriedrichMatthew T AliotaEmma L MohrThaddeus G GolosZika virus (ZIKV) can be transmitted vertically from mother to fetus during pregnancy, resulting in a range of outcomes including severe birth defects and fetal/infant death. Potential pathways of vertical transmission in utero have been proposed but remain undefined. Identifying the timing and routes of vertical transmission of ZIKV may help us identify when interventions would be most effective. Furthermore, understanding what barriers ZIKV overcomes to effect vertical transmission may help improve models for evaluating infection by other pathogens during pregnancy. To determine the pathways of vertical transmission, we inoculated 12 pregnant rhesus macaques with an African-lineage ZIKV at gestational day 30 (term is 165 days). Eight pregnancies were surgically terminated at either seven or 14 days post-maternal infection. Maternal-fetal interface and fetal tissues and fluids were collected and evaluated for ZIKV using RT-qPCR, in situ hybridization, immunohistochemistry, and plaque assays. Four additional pregnant macaques were inoculated and terminally perfused with 4% paraformaldehyde at three, six, nine, or ten days post-maternal inoculation. For these four cases, the entire fixed pregnant uterus was evaluated with in situ hybridization for ZIKV RNA. We determined that ZIKV can reach the MFI by six days after infection and infect the fetus by ten days. Infection of the chorionic membrane and the extraembryonic coelomic fluid preceded infection of the fetus and the mesenchymal tissue of the placental villi. We did not find evidence to support a transplacental route of ZIKV vertical transmission via infection of syncytiotrophoblasts or villous cytotrophoblasts. The pattern of infection observed in the maternal-fetal interface provides evidence of paraplacental vertical ZIKV transmission through the chorionic membrane, the outer layer of the fetal membranes.https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1011274&type=printable |
| spellingShingle | Michelle R Koenig Ann M Mitzey Xiankun Zeng Leticia Reyes Heather A Simmons Terry K Morgan Ellie K Bohm Julia C Pritchard Jenna A Schmidt Emily Ren Fernanda B Leyva Jaimes Eva Winston Puja Basu Andrea M Weiler Thomas C Friedrich Matthew T Aliota Emma L Mohr Thaddeus G Golos Vertical transmission of African-lineage Zika virus through the fetal membranes in a rhesus macaque (Macaca mulatta) model. PLoS Pathogens |
| title | Vertical transmission of African-lineage Zika virus through the fetal membranes in a rhesus macaque (Macaca mulatta) model. |
| title_full | Vertical transmission of African-lineage Zika virus through the fetal membranes in a rhesus macaque (Macaca mulatta) model. |
| title_fullStr | Vertical transmission of African-lineage Zika virus through the fetal membranes in a rhesus macaque (Macaca mulatta) model. |
| title_full_unstemmed | Vertical transmission of African-lineage Zika virus through the fetal membranes in a rhesus macaque (Macaca mulatta) model. |
| title_short | Vertical transmission of African-lineage Zika virus through the fetal membranes in a rhesus macaque (Macaca mulatta) model. |
| title_sort | vertical transmission of african lineage zika virus through the fetal membranes in a rhesus macaque macaca mulatta model |
| url | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1011274&type=printable |
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