Zika Virus Human Infection During Pregnancy Triggers a Strong and Broad Systemic Inflammatory Response

Abstract

Infection by the Zika virus (ZIKV) results in a broad spectrum of disease ranging from mild to severe neurological complications. The clinical features of ZIKV human infection are similar in pregnant women compared with nonpregnant women, though symptomatic infection is more frequent during pregnancy. However, little is known about the profile of systemic immune mediators during ZIKV infection in pregnant women. To characterize immunological mediators in ZIKV infection during pregnancy, we measured the levels of circulating cytokines, chemokines, and growth factors by multiplex immunoassay in 32 pregnant women, categorized according to trimesters of pregnancy. ZIKV-infected pregnant women presented higher levels of the cytokines IL-1β, IL-6, TNF-α, IL-12, IFN-γ, IL-17, IL-1Ra, IL-4, IL-5, IL-9, and IL-10 than healthy women. Moreover, a set of pro-inflammatory biomarkers, including IL-1β, IL-6, TNF-α, IL-12, IFN-γ, CCL11, and G-CSF, showed significant increased levels in the gestational second trimester than in the first trimester, which remains elevated throughout the third trimester. In conclusion, our findings indicate that ZIKV human infection during pregnancy triggers a strong and broad systemic inflammatory response, and during the viral infection, their kinetics of the production varied according to the gestational age.