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.

Details

Title
Cross-reactive Dengue virus-specific CD8+ T cells protect against Zika virus during pregnancy
Author
Regla-Nava, Jose Angel 1 ; Annie Elong Ngono 1 ; Viramontes, Karla M 1 ; Huynh, Anh-Thy 1 ; Ying-Ting, Wang 1 ; Nguyen, Anh-Viet T 1 ; Salgado, Rebecca 1 ; Mamidi, Anila 1 ; Kim, Kenneth 1 ; Diamond, Michael S 2 ; Shresta, Sujan 3 

 Division of Inflammation Biology, La Jolla Institute for Allergy & Immunology, La Jolla, CA, USA 
 Department of Medicine, Molecular Microbiology, Pathology, and Immunology, Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, St. Louis, MO, USA 
 Division of Inflammation Biology, La Jolla Institute for Allergy & Immunology, La Jolla, CA, USA; Department of Medicine, School of Medicine, University of California, San Diego, La Jolla, CA, USA 
Pages
1-14
Publication year
2018
Publication date
Aug 2018
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2082079376
Copyright
© 2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.