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Prenatal exposure to Zika virus shapes offspring neutrophil function in a sex-specific manner

Author

Listed:
  • Jiahui Ding

    (Wayne State University
    Wayne State University)

  • Anna Hu

    (Wayne State University
    University of Georgia)

  • Annie Thy Nguyen

    (Wayne State University
    Wayne State University)

  • Grace M. Swanson

    (Wayne State University
    Wayne State University)

  • Aditi Singh

    (Wayne State University)

  • Nicholas Adzibolosu

    (Wayne State University)

  • Diana Manchorova

    (Wayne State University)

  • Elizabeth Findeis

    (Wayne State University)

  • Anthony Maxwell

    (Wayne State University)

  • Yuan He

    (Wayne State University)

  • Marta Rodriguez Garcia

    (Wayne State University
    Wayne State University)

  • Gil Mor

    (Wayne State University)

Abstract

Maternal viral infection during pregnancy can have lasting consequences on offspring immune development. Zika virus (ZIKV) is known to trigger maternal immune activation (MIA), yet its impact on fetal and postnatal innate immunity remains poorly understood. Here, we investigate how prenatal exposure to ZIKV influences offspring neutrophil function using a murine model of maternal infection. We identify a sex-dimorphic placental response to ZIKV and observed hyperinflammation in ZIKV-exposed male offspring following LPS challenge. Functional assays reveal impaired reactive oxygen species production and defective neutrophil extracellular trap formation in neutrophils from ZIKV-exposed offspring. Furthermore, we identify A20 as a key sex-dimorphic regulator of neutrophil activation and survival. Here, we show that maternal viral infection during pregnancy programs long-term offspring immunity in a sex-specific manner, providing insights into the developmental origins of differential susceptibility to infections and inflammatory diseases later in life.

Suggested Citation

  • Jiahui Ding & Anna Hu & Annie Thy Nguyen & Grace M. Swanson & Aditi Singh & Nicholas Adzibolosu & Diana Manchorova & Elizabeth Findeis & Anthony Maxwell & Yuan He & Marta Rodriguez Garcia & Gil Mor, 2025. "Prenatal exposure to Zika virus shapes offspring neutrophil function in a sex-specific manner," Nature Communications, Nature, vol. 16(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-63941-x
    DOI: 10.1038/s41467-025-63941-x
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