Long-Term, Sex-Specific Immune Alterations in Fetuses Exposed to Zika Virus, Study Finds

A recent study published in Nature Communications by researchers at Wayne State University has highlighted the enduring impact of prenatal Zika virus exposure on the immune system of offspring. Led by Dr. Jiahui Ding, the research reveals that fetuses exposed to Zika in utero develop long-lasting, sex-specific immune changes, especially affecting immune cells responsible for fighting infections.

The study demonstrates that even mild or asymptomatic Zika infections during pregnancy can trigger inflammatory responses in the placenta that permanently influence how the child's immune system matures. Notably, male offspring tend to be more adversely affected, exhibiting slower growth rates and exaggerated, delayed inflammatory reactions when later challenged with bacterial stimuli. These findings imply a higher risk of chronic inflammation and tissue damage as they age.

The researchers observed distinct responses in the placenta based on sex: male placentas showed stronger activation of immune signaling pathways like IFN-β and IL-1β, whereas female placentas favored metabolic adaptations. Interestingly, the virus itself did not reach the fetus in their mouse model; instead, the immune response of the placenta significantly impacted the developing offspring.

At the cellular level, the study found that neutrophils—key components of the innate immune system—had compromised functions in offspring exposed to Zika. Their ability to produce reactive oxygen species and form Neutrophil Extracellular Traps (NETs) was diminished, impairing their capacity to combat infectious agents efficiently. The protein A20 was identified as a key regulator in neutrophil function, especially in males, where its upregulation contributed to dampened inflammatory responses and increased cell survival.

Dr. Ding emphasized the broader implications, stating, "Prenatal exposure to Zika can raise susceptibility to infections and inflammatory diseases later in life, even in children who appear healthy at birth." The findings underscore the importance of monitoring immune health in children born to mothers infected during pregnancy and suggest that similar immune alterations may occur with other viral infections such as COVID-19. Ultimately, this research reinforces the critical need to prevent viral transmission to pregnant women, particularly in high-risk areas.

This pioneering research was supported by a team including Anna Hu, Annie Thy Nguyen, and others from Wayne State University, further expanding our understanding of how prenatal viral exposures can shape lifelong immune health.

Source: https://medicalxpress.com/news/2025-10-fetuses-exposed-zika-virus-term.html