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Cross-reactive Dengue virus-specific CD8+ T cells protect against Zika virus during pregnancy

Author

Listed:
  • Jose Angel Regla-Nava

    (La Jolla Institute for Allergy & Immunology)

  • Annie Elong Ngono

    (La Jolla Institute for Allergy & Immunology)

  • Karla M. Viramontes

    (La Jolla Institute for Allergy & Immunology)

  • Anh-Thy Huynh

    (La Jolla Institute for Allergy & Immunology)

  • Ying-Ting Wang

    (La Jolla Institute for Allergy & Immunology)

  • Anh-Viet T. Nguyen

    (La Jolla Institute for Allergy & Immunology)

  • Rebecca Salgado

    (La Jolla Institute for Allergy & Immunology)

  • Anila Mamidi

    (La Jolla Institute for Allergy & Immunology)

  • Kenneth Kim

    (La Jolla Institute for Allergy & Immunology)

  • Michael S. Diamond

    (Washington University School of Medicine)

  • Sujan Shresta

    (La Jolla Institute for Allergy & Immunology
    University of California, San Diego)

Abstract

As Zika virus (ZIKV) emerges into Dengue virus (DENV)-endemic areas, cases of ZIKV infection in DENV-immune pregnant women may rise. Here we show that prior DENV immunity affects maternal and fetal ZIKV infection in pregnancy using sequential DENV and ZIKV infection models. Fetuses in ZIKV-infected DENV-immune dams were normal sized, whereas fetal demise occurred in non-immune dams. Moreover, reduced ZIKV RNA is present in the placenta and fetuses of ZIKV-infected DENV-immune dams. DENV cross-reactive CD8+ T cells expand in the maternal spleen and decidua of ZIKV-infected dams, their depletion increases ZIKV infection in the placenta and fetus, and results in fetal demise. The inducement of cross-reactive CD8+ T cells via peptide immunization or adoptive transfer results in decreased ZIKV infection in the placenta. Prior DENV immunity can protect against ZIKV infection during pregnancy in mice, and CD8+ T cells are sufficient for this cross-protection. This has implications for understanding the natural history of ZIKV in DENV-endemic areas and the development of optimal ZIKV vaccines.

Suggested Citation

  • Jose Angel Regla-Nava & Annie Elong Ngono & Karla M. Viramontes & Anh-Thy Huynh & Ying-Ting Wang & Anh-Viet T. Nguyen & Rebecca Salgado & Anila Mamidi & Kenneth Kim & Michael S. Diamond & Sujan Shrest, 2018. "Cross-reactive Dengue virus-specific CD8+ T cells protect against Zika virus during pregnancy," Nature Communications, Nature, vol. 9(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-05458-0
    DOI: 10.1038/s41467-018-05458-0
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