Contributions of maternal and fetal antiviral immunity in congenital disease
Abstract
Viral infections during pregnancy can have devastating consequences on pregnancy outcomes, fetal development, and maternal health. In this review, we examine fetal and maternal immune defense mechanisms that mediate resistance against viral infections and discuss the range of syndromes that ensue when such mechanisms fail, from fetal developmental defects to establishment of chronic infection. Further, we highlight the role of maternal immune activation, or uncontrolled inflammation triggered by viral infections during pregnancy, and its potential downstream pathological effects, including tissue damage and fetal demise. Insights into the respective contributions of direct viral toxicity versus fetal and maternal immune responses that underlie the pathogenesis of congenital disease will guide future treatment strategies.
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Zika virus can infect cortical neurons and glial cells in the fetus, resulting in cell death, neuroinflammation and severe congenital malformations.
“Zika virus can infect cortical neurons and glial cells in the fetus, resulting in cell death, neuroinflammation and severe congenital malformations221.”
From mRNA vaccines for infectious diseases: principles, delivery and clinical translation (2021) · cites this paper as [221]
Cites
Maternal Immune Activation Alters Fetal Brain Development through Interleukin-6
Smith, S. E. P., Li, J., Garbett, K., Mirnics, K., & Patterson, P. H. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.2178-07.2007 · Cited by 1,605 · see citing works
Mascio, D. D., Khalil, A. A., Saccone, G., Rizzo, G., Buca, D. I. P., Liberati, M., Vecchiet, J., Nappi, L., Scambia, G., Berghella, V., et al. (2020) · American Journal of Obstetrics & Gynecology MFM · doi:10.1016/j.ajogmf.2020.100107 · Cited by 1,321 · see citing works
Zika Virus Infects Human Cortical Neural Progenitors and Attenuates Their Growth
Tang, H., Hammack, C., Ogden, S. C., Wen, Z., Qian, X., Li, Y., Yao, B., Shin, J., Zhang, F., Lee, E. M., et al. (2016) · Cell Stem Cell · doi:10.1016/j.stem.2016.02.016 · Cited by 1,292 · see citing works
The maternal interleukin-17a pathway in mice promotes autism-like phenotypes in offspring
Choi, G. B., Yim, Y. S., Wong, H., Kim, S., Kim, H., Kim, S. V., Hoeffer, C. A., Littman, D. R., & Huh, J. R. (2016) · Science · doi:10.1126/science.aad0314 · Cited by 1,214 · see citing works
The unique immunological and microbial aspects of pregnancy
Mor, G., Aldo, P., & Alvero, A. B. (2017) · Nature Reviews Immunology · doi:10.1038/nri.2017.64 · Cited by 1,041 · see citing works
The “Silent” Global Burden of Congenital Cytomegalovirus
Manicklal, S., Emery, V. C., Lazzarotto, T., Boppana, S. B., & Gupta, R. K. (2013) · Clinical Microbiology Reviews · doi:10.1128/cmr.00062-12 · Cited by 1,030 · see citing works
Aicardi–Goutières syndrome and the type I interferonopathies
Crow, Y. J., & Manel, N. (2015) · Nature Reviews Immunology · doi:10.1038/nri3850 · Cited by 925 · see citing works
Zika Virus Disrupts Neural Progenitor Development and Leads to Microcephaly in Mice
Li, C., Xu, D., Ye, Q., Hong, S., Jiang, Y., Liu, X., Zhang, N., Shi, L., Qin, C.-F., & Xu, Z. (2016) · Cell Stem Cell · doi:10.1016/j.stem.2016.04.017 · Cited by 749 · see citing works
Clinical Characteristics of Pregnant Women with Covid-19 in Wuhan, China
Chen, L., Li, Q., Zheng, D., Jiang, H., Wei, Y., Zou, L. P., Feng, L., Xiong, G., Sun, G., Wang, H., et al. (2020) · New England Journal of Medicine · doi:10.1056/nejmc2009226 · Cited by 625 · see citing works
Couderc, T., Chrétien, F. C., Schilte, C., Disson, O., Brigitte, M., Guivel‐Benhassine, F., Touret, Y., Barau, G., Cayet, N., Schuffenecker, I., et al. (2008) · PLoS Pathogens · doi:10.1371/journal.ppat.0040029 · Cited by 621 · see citing works
Bayer, A., Lennemann, N. J., Ouyang, Y., Bramley, J. C., Morosky, S. A., Marques, E. T. A., Cherry, S. R., Sadovsky, Y., & Coyne, C. B. (2016) · Cell Host & Microbe · doi:10.1016/j.chom.2016.03.008 · Cited by 549 · see citing works
Microbial Vertical Transmission during Human Pregnancy
Arora, N., Sadovsky, Y., Dermody, T. S., & Coyne, C. B. (2017) · Cell Host & Microbe · doi:10.1016/j.chom.2017.04.007 · Cited by 384 · see citing works
Reversing behavioural abnormalities in mice exposed to maternal inflammation
Shin Yim, Y., Park, A., Berrios, J., Lafourcade, M., Pascual, L. M., Soares, N., Yeon Kim, J., Kim, S., Kim, H., Waisman, A., et al. (2017) · Nature · doi:10.1038/nature23909 · Cited by 303 · see citing works
Neu, N. M., Duchon, J. M., & Zachariah, P. (2014) · Clinics in Perinatology · doi:10.1016/j.clp.2014.11.001 · Cited by 291 · see citing works
Mature CD8+ T lymphocyte response to viral infection during fetal life
Marchant, A., Appay, V., van der Sande, M. A. B., Dulphy, N., Liesnard, C., Kidd, M., Kaye, S., Ojuola, O. O., Gillespie, G. M. A., Cuero, A. L. V., et al. (2003) · Journal of Clinical Investigation · doi:10.1172/jci17470 · Cited by 269 · see citing works
The fetal origins of mental illness
al-Haddad, B. J. S., Oler, E., Armistead, B., Elsayed, N. A., Weinberger, D. R., Bernier, R., Burd, I. D., Kapur, R. P., Jacobsson, B., Wang, C., et al. (2019) · American Journal of Obstetrics and Gynecology · doi:10.1016/j.ajog.2019.06.013 · Cited by 265 · see citing works
Type I interferons instigate fetal demise after Zika virus infection
Yockey, L. J., Jurado, K. A., Arora, N., Millet, A., Rakib, T., Milano, K. M., Hastings, A. K., Fikrig, E., Kong, Y., Horváth, T. L., et al. (2018) · Science Immunology · doi:10.1126/sciimmunol.aao1680 · Cited by 253 · see citing works
Self-citationCardenas, I., Means, R. E., Aldo, P. B., Koga, K., Lang, S. M., Booth, C. J., Alejandro Manzur, Y., Enrique Oyarzún, E., Romero, R. J., & Mor, G. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.1000289 · Cited by 248 · see citing works
Mother-to-Child Transmission of Chikungunya Virus Infection
Ramful, D., Carbonnier, M., Pasquet, M., et al. (2007) · The Pediatric Infectious Disease Journal · doi:10.1097/inf.0b013e3180616d4f · Cited by 243 · see citing works
Hepatitis E and pregnancy: current state
Pérez‐Gracia, M. T., Suay‐García, B., & Mateos‐Lindemann, M. L. (2017) · Reviews in Medical Virology · doi:10.1002/rmv.1929 · Cited by 241 · see citing works
Gérardin, P., Sampériz, S., Ramful, D., Boumahni, B., Bintner, M., Alessandri, J., Carbonnier, M., Tiran-Rajaofera, I., Beullier, G., Boya, I., et al. (2014) · PLoS neglected tropical diseases · doi:10.1371/journal.pntd.0002996 · Cited by 229 · see citing works
Mature CD8+ T lymphocyte response to viral infection during fetal life
Marchant, A., Appay, V., van der Sande, M. A. B., et al. (2003) · Journal of Clinical Investigation · doi:10.1172/jci200317470 · Cited by 229 · see citing works
Hofbauer Cells: Their Role in Healthy and Complicated Pregnancy
Reyes, L., & Golos, T. G. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.02628 · Cited by 200 · see citing works
Human Cytomegalovirus Infection Elicits New Decidual Natural Killer Cell Effector Functions
Siewiera, J., Costa, H. E., Tabiasco, J., Berrebi, A., Cartron, G., Bouteiller, P. P. L., & Jabrane‐Ferrat, N. (2013) · PLoS Pathogens · doi:10.1371/journal.ppat.1003257 · Cited by 167 · see citing works
Congenital Viral Infection: Traversing the Uterine-Placental Interface
Pereira, L. (2018) · Annual Review of Virology · doi:10.1146/annurev-virology-092917-043236 · Cited by 166 · see citing works
IFITM proteins inhibit placental syncytiotrophoblast formation and promote fetal demise
Buchrieser, J., Degrelle, S. A., Couderc, T., Nevers, Q., Disson, O., Manet, C., Donahue, D. A., Porrot, F., Hillion, K.-H., Perthame, É., et al. (2019) · Science · doi:10.1126/science.aaw7733 · Cited by 161 · see citing works
van der Zwan, A., Bi, K., Norwitz, E. R., Crespo, Â. C., Claas, F. H. J., Strominger, J. L., & Tilburgs, T. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1713957115 · Cited by 153 · see citing works
The Immune System of HIV-Exposed Uninfected Infants
Abu-Raya, B., Kollmann, T. R., Marchant, A., et al. (2016) · Frontiers in Immunology · doi:10.3389/fimmu.2016.00383 · Cited by 145 · see citing works
Ito, H., Smith, S. E. P., Hsiao, E. Y., & Patterson, P. H. (2010) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2010.03.004 · Cited by 133 · see citing works
Features of Human Decidual NK Cells in Healthy Pregnancy and During Viral Infection
Jabrane‐Ferrat, N. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.01397 · Cited by 127 · see citing works
Neonatal Herpes Simplex Virus Infection
James, S. H., & Kimberlin, D. W. (2015) · Infectious Disease Clinics of North America · doi:10.1016/j.idc.2015.05.001 · Cited by 116 · see citing works
A Novel FcγR-Defined, IgG-Containing Organelle in Placental Endothelium
Takizawa, T., Anderson, C. L., & Robinson, J. M. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.175.4.2331 · Cited by 94 · see citing works
Scott, G. M., Chow, S. S. W., Craig, M. E., Pang, C. N. I., Hall, B., Wilkins, M. R., Jones, C., Lloyd, A. R., & Rawlinson, W. D. (2012) · The Journal of Infectious Diseases · doi:10.1093/infdis/jis186 · Cited by 83 · see citing works
Herpes simplex virus blocks intracellular transport of HLA-G in placentally derived human cells
Schust, D. J., Hill, A. B., & Ploegh, H. L. (1996) · The Journal of Immunology · doi:10.4049/jimmunol.157.8.3375 · Cited by 73 · see citing works
Cerebral palsy and placental infection: a case-cohort study
Vigneswaran, R., Aitchison, S., McDonald, H. M., Khong, T. Y., & Hiller, J. E. (2004) · BMC Pregnancy and Childbirth · doi:10.1186/1471-2393-4-1 · Cited by 71 · see citing works
Interferon-induced transmembrane proteins inhibit cell fusion mediated by trophoblast syncytins
Zani, A., Zhang, L., McMichael, T. M., et al. (2019) · Journal of Biological Chemistry · doi:10.1074/jbc.ac119.010611 · Cited by 69 · see citing works
Puerta-Guardo, H. N., Tabata, T., Petitt, M., Dimitrova, M. A., Glasner, D. R., Pereira, L., & Harris, E. (2019) · The Journal of Infectious Diseases · doi:10.1093/infdis/jiz331 · Cited by 63 · see citing works
Perinatal Cytomegalovirus and Varicella Zoster Virus Infections
Bialas, K. M., Swamy, G. K., & Permar, S. R. (2015) · Clinics in Perinatology · doi:10.1016/j.clp.2014.10.006 · Cited by 54 · see citing works
Slatter, T. L., Hung, N. G., Clow, W. M., Royds, J. A., Devenish, C. J., & Hung, N. A. (2015) · Modern Pathology · doi:10.1038/modpathol.2015.88 · Cited by 54 · see citing works
Quillay, H., Costa, H. E., Duriez, M., et al. (2016) · Retrovirology · doi:10.1186/s12977-016-0271-z · Cited by 52 · see citing works
Herpes simplex virus infection of cultured human term trophoblast
Nørskov‐Lauritsen, N., ABoagye-Mathisen, G., Juhl, C. B., et al. (1992) · Journal of Medical Virology · doi:10.1002/jmv.1890360303 · Cited by 28 · see citing works
HIV Infection: Antepartum Treatment and Management
Bernstein, H. B., & Wegman, A. D. (2018) · Clinical Obstetrics & Gynecology · doi:10.1097/grf.0000000000000330 · Cited by 24 · see citing works
Liu, T., Zheng, X., Li, Q., et al. (2015) · PubMed · Cited by 21 · see citing works
Maturation of the immune system in the fetus and the implications for congenital CMV
Rechavi, E., & Somech, R. (2019) · Best Practice & Research Clinical Obstetrics & Gynaecology · doi:10.1016/j.bpobgyn.2019.03.002 · Cited by 14 · see citing works
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Gote, V., Bolla, P. K., Kommineni, N., Butreddy, A., Nukala, P. K., Palakurthi, S. S., & Khan, W. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24032700 · Cited by 457 · see citing works
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- Authors
- Yockey, L. J., Lucas, C., & Iwasaki, A.
- Affiliations
- Yale University (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Yockey, Laura J.
- Lucas, Carolina
- Iwasaki, Akiko
- Venue
- Science
- Published
- 2020-05-08
- Volume
- 368
- Issue
- 6491
- Pages
- 608-612
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W3023140579
- Cited by
- 68
- References
- 44
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 7 · 2023: 9 · 2022: 15 · 2021: 22 · 2020: 9
- FWCI
- 1.34
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (AI054359, AI127429)
- Howard Hughes Medical Institute (N/A)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Reproductive System and Pregnancy
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Health Sciences › Medicine › Epidemiology › Cytomegalovirus and herpesvirus research
- Keywords
- congenital viral infection, maternal immune activation, chronic viral infection, intrauterine fetal death, inflammation, pregnancy outcomes
- MeSH terms
- Female, Fetal Diseases, Fetus, Humans, Immunity, Innate, Maternal-Fetal Exchange, Pregnancy, Pregnancy Complications, Infectious, Pregnancy Outcome, Virus Diseases, Fetal Development
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