Mechanistic insights into the impact of prenatal viral infections on maternal and offspring immunity

Gielenny M Salem; Tamiris Azamor; Débora Familiar-Macedo; Chineme Onwubueke; Mary Catherine Cambou; Weiqiang Chen; Karin Nielsen-Saines; Suan-Sin Foo

doi:10.1038/s44298-026-00174-9

Mechanistic insights into the impact of prenatal viral infections on maternal and offspring immunity

Npj Viruses. 2026 Jan 28;4(1):7. doi: 10.1038/s44298-026-00174-9.

Authors

Gielenny M Salem¹, Tamiris Azamor^{1

2}, Débora Familiar-Macedo¹, Chineme Onwubueke¹, Mary Catherine Cambou³, Weiqiang Chen^{1

4}, Karin Nielsen-Saines³, Suan-Sin Foo^{5

6}

Affiliations

¹ Department of Infection Biology, Cleveland Clinic, Cleveland, OH, USA.
² Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brazil.
³ Department of Medicine, Division of Infectious Diseases, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
⁴ Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH, USA.
⁵ Department of Infection Biology, Cleveland Clinic, Cleveland, OH, USA. foos@ccf.org.
⁶ Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH, USA. foos@ccf.org.

Abstract

Global outbreaks of human immunodeficiency virus (HIV) and respiratory viruses - severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza, accounted for ~50 million infections in 2024. Prenatal exposure to these viruses poses substantial risks to maternal and fetal health, yet the underlying immunological mechanisms remain incompletely understood. Despite differences in viral biology and transmission, mounting evidence reveals a convergent theme of maternal immune activation during pregnancy. Even without vertical transmission, virus-elicted maternal immune responses alter the maternal-fetal interface and gut microbiome, reshaping fetal immunity and birth outcomes. These immune perturbations increase susceptibility to infections, neurodevelopmental disorders, and immune-mediated diseases later in life. Here, we discuss viral immune evasion strategies that modulate maternal immunity and review current clinical and emerging therapeutic approaches aimed at mitigating long-term consequences in exposed children. Understanding how prenatal viral exposure shapes lifelong health is critical for developing targeted interventions and reducing postnatal disease burden.

Publication types

Review

Grants and funding

N/A/Cleveland Clinic