Exposure to the Zika virus during pregnancy permanently shapes the frontline immune cells of offspring

Exposure to the Zika virus during pregnancy permanently shapes the frontline immune cells of offspring

A Wayne State University study published in the October 3, 2025 issueNature communicationfound that exposure to the Zika virus during pregnancy causes long-term, gender-specific changes in a baby's immune system, particularly affecting the front-line immune cells that fight infection.

The study, “Prenatal exposure to Zika virus affects offspring neutrophil function in a sex-specific manner,” was led by Dr. Jiahui Ding, assistant professor of obstetrics and gynecology at Wayne State School of Medicine.

We found that when a pregnant mother is infected with the Zika virus, the resulting inflammatory response in the placenta permanently alters the development of the offspring's immune system. This occurs even if the infection in the mother is mild or asymptomatic and does not result in obvious congenital birth defects in the offspring.”

Dr. Jiahui Ding, assistant professor of obstetrics and gynecology, School of Medicine, Wayne State University

Ding and her research team found that male offspring are more affected by Zika infection during pregnancy; When they were exposed to the Zika virus in the womb, they showed slower growth compared to control males. Furthermore, they showed an exaggerated and delayed inflammatory response when later exposed to a simulated bacterial infection. This finding suggests that male offspring are at higher risk of chronic inflammation and tissue damage later in life if they were exposed to the Zika virus before birth.

The research team also identified a gender effect related to how the placenta responded to the virus. Male placenta showed greater activation of immune-related signaling pathways (such as IFN-β and IL-1β), whereas female placenta showed greater metabolic adaptations. In their mouse model, the virus did not reach the fetus. Instead, it was the placental immune response that had the greatest impact on the developing offspring.

The function of neutrophils – the most critical “first responder” cells of the innate immune system – is impaired in offspring of both sexes exposed to the Zika virus. The neutrophils showed reduced production of reactive oxygen species, suggesting that they are less effective at producing the necessary toxic chemicals required to kill the viral pathogens. The team also discovered defective formation of a neutrophil extraceullar trap (NET), which resulted in an impaired ability to form the web-like NET structures used to trap and penetrate germs - a process called NETosis.

The team also identified a protein called A20 (Tnfaip3) as a key sexually dimorphic regulator of neutrophil activation and survival. The upregulation of A20 specifically in male neutrophils after Zika virus exposure likely contributes to their dampened inflammatory responsein vitroand helps promote neutrophil survival.

"Our research has shown that prenatal exposure to the Zika virus can increase a child's susceptibility to infections and inflammatory diseases later in life compared to children who were not exposed to the virus," Ding said. "Our research shows that even children who were exposed to the Zika virus prenatally and appear healthy may have altered immune defenses that require long-term monitoring. While we focused on Zika, these results may also apply to other viral infections such as COVID-19, underscoring the importance of monitoring and supporting the immune systems of virus-exposed children. Furthermore, our results underscore the ongoing need to prevent virus transmission, particularly in high-risk areas and.” among pregnant women.”

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