ZIKV can infect human term placentas in the absence of maternal factors

• Published in: Communications biology Vol. 5; no. 1; p. 243
• Main Authors: Villazana-Kretzer, Diana L., Wuertz, Kathryn McGuckin, Newhouse, Daniel, Damicis, Jennifer R., Dornisch, Elisabeth M., Voss, Kathleen M., Muruato, Antonio E., Paymaster, Jennifer A., Schmiedecke, Stacey S., Edwards, Sarah M., Napolitano, Peter G., Tisoncik-Go, Jennifer, Ieronimakis, Nicholas, Gale, Michael
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 18.03.2022; Nature Publishing Group; Nature Portfolio
• Subjects: 13/21; 13/51; 14/1; 14/19; 14/63; 38/39; 38/90; 631/250/254; 692/699/255/2514; 96/2; Apoptosis; Biology; Biomedical and Life Sciences; Cell death; Cotyledons; Female; Gene expression; Humans; Immune response; Infections; Infectious Disease Transmission, Vertical; Innate immunity; Life Sciences; Perfusion; Placenta; Pregnancy; Pregnancy Complications, Infectious - pathology; Transcription factors; Viral infections; Viruses; Zika virus; Zika Virus - physiology; Zika Virus Infection
• ISSN: 2399-3642; 2399-3642
• DOI: 10.1038/s42003-022-03158-6

Zika virus infection can result in devastating pregnancy outcomes when it crosses the placental barrier. For human pregnancies, the mechanisms of vertical transmission remain enigmatic. Utilizing a human placenta-cotyledon perfusion model, we examined Zika virus exposure in the absence of maternal factors. To distinguish responses related to viral infection vs . recognition, we evaluated cotyledons perfused with either active or inactivated Zika virus. Active Zika virus exposure resulted in infection, cell death and syncytium injury. Pathology corresponded with transcriptional changes related to inflammation and innate immunity. Inactive Zika virus exposure also led to syncytium injury and related changes in gene expression but not cell death. Our observations reveal pathologies and innate immune responses that are dependent on infection or virus placenta interactions independent of productive infection. Importantly, our findings indicate that Zika virus can infect and compromise placentas in the absence of maternal humoral factors that may be protective. Villazana-Kretzer et al. compare histology, physiology and gene expression in cotyledons from term placentas perfused with either active or UV-inactivated Zika virus. They show that ZIKV can infect human term placentas in the absence of maternal factors and identify unique transcriptional responses to active ZIKA virus.