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

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.

• Authors: 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 Shresta
• Journal: Nature communications (Nat Commun) Vol. 9 Issue 1 Pg. 3042 (08 02 2018) ISSN: 2041-1723 [Electronic] England
• PMID: 30072692 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Epitopes

Topics

• Animals
• CD8-Positive T-Lymphocytes (immunology)
• Cross Reactions (immunology)
• Decidua (pathology)
• Dengue Virus (immunology)
• Epitopes (immunology)
• Female
• Fetus (pathology)
• Mice, Inbred C57BL
• Phenotype
• Pregnancy
• Species Specificity
• Spleen (immunology, pathology)
• Viral Load
• Zika Virus (immunology)
• Zika Virus Infection (immunology, virology)