Increased Serum Levels of Growth-Differentiation Factor 3 (GDF3) and Inflammasome-Related Markers in Pregnant Women during Acute Zika Virus Infection

Viruses. 2022 May 9;14(5):1004. doi: 10.3390/v14051004.

Abstract

The systemic inflammatory response elicited by acute Zika virus (ZIKV) infection during pregnancy plays a key role in the clinical outcomes in mothers and congenitally infected offspring. The present study aimed to evaluate the serum levels of GDF-3 and inflammasome-related markers in pregnant women during acute ZIKV infection. Serum samples from pregnant (n = 18) and non-pregnant (n = 22) women with acute ZIKV infection were assessed for NLRP3, IL-1β, IL-18, and GDF3 markers through an enzyme-linked immunosorbent assay. ZIKV-negative pregnant (n = 18) and non-pregnant women (n = 15) were used as control groups. All serum markers were highly elevated in the ZIKV-infected groups in comparison with control groups (p < 0.0001). Among the ZIKV-infected groups, the serum markers were significantly augmented in the pregnant women in comparison with non-pregnant women (NLRP3 p < 0.001; IL-1β, IL-18, and GDF3 p < 0.0001). The IL-18 marker was found at significantly higher levels (p < 0.05) in the third trimester of pregnancy. Bivariate and multivariate analyses showed a strong positive correlation between GDF3 and NLRP3 markers among ZIKV-infected pregnant women (r = 0.91, p < 0.0001). The findings indicated that acute ZIKV infection during pregnancy induces the overexpression of GDF-3 and inflammasome-related markers, which may contribute to congenital disorders and harmful pregnancy outcomes.

Keywords: GDF3; IL-18; IL-1β; NLRP3; ZIKV; inflammasome; pregnancy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers
  • Female
  • Growth Differentiation Factor 3* / blood
  • Humans
  • Inflammasomes*
  • Interleukin-18
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Pregnancy
  • Pregnancy Outcome
  • Pregnant Women
  • Zika Virus Infection* / immunology

Substances

  • Biomarkers
  • GDF3 protein, human
  • Growth Differentiation Factor 3
  • Inflammasomes
  • Interleukin-18
  • NLR Family, Pyrin Domain-Containing 3 Protein

Grants and funding

This study was financed by the Conselho Nacional de Desenvolvimento Científico e Tecnológico—Brasil (CNPq)—Finance codes 420331/2016-6 and 440856/2016-7, also the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—Brasil (CAPES)—Finance code PROCAD AMAZÔNIA 88881.200581/201801 and Fundação de Amparo à Pesquisa do Estado do Amazonas (FAPEAM) POSGRAD (Resolution 006/2020).