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

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 and Sujan Shresta ()
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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

Nature Communications, 2018, vol. 9, issue 1, 1-14

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-05458-0

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