Zika Virus Targets Different Primary Human Placental Cells, Suggesting Two Routes for Vertical Transmission
Open accessAbstract
Zika virus (ZIKV) infection during pregnancy is linked to severe birth defects, but mother-to-fetus transmission routes are unknown. We infected different primary cell types from mid- and late-gestation placentas and explants from first-trimester chorionic villi with the prototype Ugandan and a recently isolated Nicaraguan ZIKV strain. ZIKV infects primary human placental cells and explants-cytotrophoblasts, endothelial cells, fibroblasts, and Hofbauer cells in chorionic villi and amniotic epithelial cells and trophoblast progenitors in amniochorionic membranes-that express Axl, Tyro3, and/or TIM1 viral entry cofactors. ZIKV produced NS3 and E proteins and generated higher viral titers in amniotic epithelial cells from mid-gestation compared to late-gestation placentas. Duramycin, a peptide that binds phosphatidylethanolamine in enveloped virions and precludes TIM1 binding, reduced ZIKV infection in placental cells and explants. Our results suggest that ZIKV spreads from basal and parietal decidua to chorionic villi and amniochorionic membranes and that targeting TIM1 could suppress infection at the uterine-placental interface.
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The explant model enabled the first demonstration of Zika virus infection of the first trimester placenta in vitro and has been used to investigate placental uptake of glucose, amino acids, and exosomes.
“The explant model enabled the first demonstration of Zika virus infection of the first trimester placenta in vitro (144) and has been used to investigate placental uptake of other substances, including glucose (145), amino acids (146), and exosomes (147).”
From Factors Affecting the FcRn-Mediated Transplacental Transfer of Antibodies and Implications for Vaccination in Pregnancy (2017) · cites this paper as [144]
The Results and Experimental Procedures describe infecting cultured chorionic villus explants from first-trimester placentas with Zika virus and detecting infection. The paper does not establish that this was the first such demonstration. The glucose, amino-acid, and exosome claims carry separate citations and are not attributed to this source. (LLM, conf=0.82)
Experimental — accuracy not yet measuredDuramycin, a class-1 bacteriocin produced by Streptomycetes, prevents Zika virus entry by blocking its co-receptor TIM1.
“duramycin, a class-1 bacteriocin produced by Streptomycetes, has been found to prevent Zika virus entry by blocking its co-receptor TIM1 (Tabata et al., 2016).”
From Viral Infections, the Microbiome, and Probiotics (2021) · cites this paper as Tabata et al., 2016
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“The explant model enabled the first demonstration of Zika virus infection of the first trimester placenta in vitro (144) and has been used to investigate placental uptake of other substances, including glucose (145), amino acids (146), and exosomes (147).”
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- Authors
- Tabata, T., Petitt, M., Puerta-Guardo, H., Michlmayr, D., Wang, C., Fang-Hoover, J., Harris, E., & Pereira, L.
- Affiliations
- University of California, San Francisco (US)
- University of California, Berkeley (US)
- Corresponding author
- Harris, Eva
- Pereira, Lenore
- Venue
- Cell Host & Microbe
- Publisher
- Elsevier BV
- Published
- 2016-08
- Volume
- 20
- Issue
- 2
- Pages
- 155-166
- ISSN
- 1931-3128 (ISSN-L)
- PMC
- PMC5257282
- OpenAlex
- W2482354067
- Cited by
- 486
- References
- 53
- Citations by year
- 2026: 13 · 2025: 33 · 2024: 26 · 2023: 30 · 2022: 39 · 2021: 64 · 2020: 52 · 2019: 60 · 2018: 57 · 2017: 85 · 2016: 27
- FWCI
- 75.68
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Host & Microbe (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institutes of Health
- National Institute of Allergy and Infectious Diseases (R01AI046657, R21AI129508, R01AI124493, P01AI106695)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Mosquito-borne diseases and control
- Health Sciences › Medicine › Infectious Diseases › Viral Infections and Outbreaks Research
- Health Sciences › Medicine › Infectious Diseases › Viral Infections and Vectors
- Keywords
- Zika virus, vertical transmission, placenta, chorionic villi, amniotic epithelial cells, Hofbauer cells, cytotrophoblast, AXL, Tyro3, TIM-1, duramycin, phosphatidylethanolamine, decidua, pregnancy, congenital malformations
- MeSH terms
- Zika Virus Infection, Zika Virus, Hepatitis A Virus Cellular Receptor 1, Antiviral Agents, Bacteriocins, Cells, Cultured, Female, Humans, Organ Culture Techniques, Peptides, Placenta, Pregnancy, Receptors, Virus, Infectious Disease Transmission, Vertical, Virus Internalization, Viral Tropism
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