Investigation of Annexin A1 protein in human placentae infected by Zika virus

Author(s)

Rafaela Batista Molás Mendes

• Document type: Master's Dissertation
• Press: São José do Rio Preto. 2019-05-16.
• Institution: Universidade Estadual Paulista (Unesp). Instituto de Biociências Letras e Ciências Exatas. São José do Rio Preto
• Defense date: 2019-04-03
• Advisor: Sonia Maria Oliani; Jusciele Brogin Moreli

Abstract

Introduction: The association of Zika virus infection (ZIKV) with congenital malformation and neurological sequelae brought a significant global concern. Recent studies have shown that maternal viral infection induces inflammation in the placental tissue. In this context, the antiinflammatory protein annexin 1 (ANXA1) has been specially related to resolution of inflammation through multiple mechanisms and associated with antiparasitic activity in infected placental explants. Although these effects have been explored in several investigations, its activities have not yet been fully elucidated in placentas infected with ZIKV. Objectives: This study was conducted to evaluate the involvement of ANXA1 in placentas of ZIKV-infected mothers. Methods: With maternal blood and placenta, using the rt-PCR techinique, It was classified three study groups: Neg/Neg (mother and placenta negative for the virus), Pos/Neg (infected mother, but no virus detected in placenta) and Pos/Pos (mother and placenta infected with ZIKV). Placental fragments were fixed, embedded in paraffin and analyzed for the presence of ZIKV (anti-flavivirus 4g2), structurally, and immunohistochemistry for trophoblast (cytokeratin), mesenchymal and endothelial cells (vimentin) and arterial vessels (α-sma). Inflammatory cells were analyzed by immunofluorescence (CD-3, CD-15 and CD45 positive cells) and levels of the cytokines IL-1β, IL-6, IL-10, TNF-α, IL-8 by the Magpix Multiplex analyzer. ANXA1 expression was assessed by immunohistochemistry, Western blot and real-time PCR. Results: The presence of ZIKV in the Pos/Pos group shows placentas with structural alterations, including detachment and disorganization of the syncyciotrophoblast. Maternal infection by ZIKV triggered an placental inflammatory response, observed by recruitment of inflammatory cells and increased levels of cytokines. In the syncytiotrophoblast, ANXA1 was expressed in nuclei and cytoplasm, and its expression was decreased in mother/placenta infected specimens. These results points to a mechanism of placental defense to avoid infection. In summary, our results show that maternal infection with ZIKV is able to develop a placental inflammatory response, which might be related to the ANXA1 modulation. These data are innovative and might open a new path of future exploration of this protein mechanism of action in the gestational process. (AU)

• FAPESP's process: 17/09136-3 - Annexin A1 protein: characterization and function in placentas infected with ZIKA virus
• Grantee: Rafaela Batista Molás Mendes
• Support Opportunities: Scholarships in Brazil - Master