Pregnant Women Infected with Zika Virus Show Higher Viral Load and Immunoregulatory Cytokines Profile with CXCL10 Increase.

Elizabeth Camacho-Zavala,Cesar R. Gonzalez-Bonilla,Clara Santacruz-Tinoco,Rommel Chacón-Salinas,Victor Hugo Borja-Aburto,Thomas Jaenisch,Concepción Grajales,Joaquin González-Ibarra,Ma Isabel Salazar-Sanchez,Esteban Muñoz

doi:10.3390/v13010080

Abstract

Background: Zika virus (ZIKV) infection during pregnancy usually shows only mild symptoms and is frequently subclinical. However, it can be vertically transmitted to the fetus, causing microcephaly and other congenital defects. During pregnancy, the immune environment modifications can alter the response to viruses in general and ZIKV in particular. Objective: To describe the role of pregnancy in the systemic pro- and anti-inflammatory response during symptomatic ZIKV infection. Materials and Methods: A multiplex assay was used to measure 25 cytokines, chemokines, and receptors in 110 serum samples from pregnant and nonpregnant women with and without ZIKV infection with and without symptoms. Samples were collected through an epidemiological surveillance system. Results: Samples from pregnant women with ZIKV infection showed a higher viral load but had similar profiles of inflammatory markers as compared with nonpregnant infected women, except for CXCL10 that was higher in infected pregnant women. Notably, the presence of ZIKV in pregnancy favored a regulatory profile by significantly increasing anti-inflammatory cytokines such as interleukin (IL)-10, receptors IL-1RA, and IL-2R, but only those pro-inflammatory cytokines such as IL-6, interferon (IFN)-α, IFN-γ and IL-17 that are essential for the antiviral response. Interestingly, there were no differences between symptomatic and weakly symptomatic ZIKV-infected groups. Conclusion: Our results revealed a systemic anti-inflammatory cytokine and chemokine profile that could participate in the control of the virus. The anti-inflammatory response in pregnant women infected with ZIKA was characterized by high CXCL10, a cytokine that has been correlated with congenital malformations.

Highlights

Zika virus (ZIKV) is a flavivirus transmitted by the bite of female mosquitoes of the genus Aedes, mainly A. aegypti and to a lesser degree A. albopictus
Group one (NPH) comprised 14 nonpregnant healthy women with mean age 26.6, ±7.6 years; Group two (NPZ+) included 22 samples from nonpregnant ZIKV-positive women with mean age 30.6, ±6.7 years; Group three (PH) comprised 30 samples from pregnant healthy ZIKV-negative women with mean age 27.1, ±6.7; Group four (PWZ+) included samples from pregnant women with ZIKV infection who did not meet the operational definition of Zika and were considered weakly symptomatic, mean 30.1 ±5.6 years; and Group five (PSZ+) included 25 samples from pregnant women with confirmed symptomatic ZIKV infection with mean age 26.9, ±3.9 years
The samples from pregnant women positive for ZIKV infection were collected through the IMSS epidemiological surveillance system, and patient records were reviewed to divide the patients into two groups: those who met the operational definition of Zika fever and those who, despite having some clinical manifestations, did not meet this definition, and were considered weakly symptomatic

Summary

Introduction

Zika virus (ZIKV) is a flavivirus transmitted by the bite of female mosquitoes of the genus Aedes, mainly A. aegypti and to a lesser degree A. albopictus. Over the five years, the disease spread to Polynesia, Easter Island, the Cook Islands, and New Caledonia and was introduced and disseminated rapidly in South America in 2015 and to Central America and the Caribbean, including Mexico, the following year [2,3,4] After these large epidemics, ZIKV infection has remained endemic with a low transmission rate in South and Central America, including Mexico, Peru, and Colombia. Objective: To describe the role of pregnancy in the systemic pro- and anti-inflammatory response during symptomatic ZIKV infection. Materials and Methods: A multiplex assay was used to measure 25 cytokines, chemokines, and receptors in 110 serum samples from pregnant and nonpregnant women with and without ZIKV infection with and without symptoms. The anti-inflammatory response in pregnant women infected with ZIKA was characterized by high CXCL10, a cytokine that has been correlated with congenital malformations

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