Journal Article

Vertical transmission of African-lineage Zika virus through the fetal membranes in a rhesus macaque (Macaca mulatta) model

Bohm, Ellie K., Mitzey, Ann M., Golos, Thaddeus G., Schmidt, Jenna A., Leyva Jaimes, Fernanda B., Winston, Eva, Pritchard, Julia C., Basu, Puja, Aliota, Matthew T., Ren, Emily, Morgan, Terry K., Weiler, Andrea M., Simmons, Heather A., Koenig, Michelle R., Zeng, Xiankun, Mohr, Emma L., Friedrich, Thomas C., Reyes, Leticia

2023

Overview

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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Achievement tests / Analysis / Animals / Biology and life sciences / Birth defects / Congenital defects / Disease transmission / Euthanasia / Extraembryonic Membranes - metabolism / Female / Fetal Death / Fetuses / Gestational age / Health aspects / Humans / Hybridization / Immunohistochemistry / Infant mortality / Infection / Infections / Infectious Disease Transmission, Vertical / Inoculation / Macaca mulatta / Medicine and Health Sciences / Membranes / Miscarriage / Placenta / Pregnancy / Pregnancy Complications, Infectious - metabolism / Pregnant women / Research and analysis methods / Uterus / Vector-borne diseases / Viruses / Zika virus / Zika Virus - genetics / Zika Virus Infection