Decidual production of interferon lambda in response to ZIKV persistence: Clinical evidence and in vitro modelling

Tamiris Azamor; Daniela Prado Cunha; Keyla Silva Nobre Pires; Eloiza Lopes Lira Tanabe; Juliana Gil Melgaço; Andréa Marques Vieira da Silva; Marcelo Ribeiro-Alves; Thyago Leal Calvo; Luciana Neves Tubarão; Jane da Silva; Camilla Bayma Fernandes; Alessandro Fonseca de Souza; Amanda Torrentes de Carvalho; Elyzabeth Avvad-Portari; Letícia da Cunha Guida; Leonardo Gomes; Maria Elisabeth Lopes Moreira; Ana Paula Dinis Ano Bom; Patrícia Cristina da Costa Neves; Sotiris Missailidis; Zilton Vasconcelos; Alexandre Urban Borbely; Milton Ozório Moraes

doi:10.1016/j.heliyon.2024.e30613

Decidual production of interferon lambda in response to ZIKV persistence: Clinical evidence and in vitro modelling

Heliyon. 2024 May 3;10(9):e30613. doi: 10.1016/j.heliyon.2024.e30613. eCollection 2024 May 15.

Authors

Tamiris Azamor¹, Daniela Prado Cunha¹, Keyla Silva Nobre Pires², Eloiza Lopes Lira Tanabe², Juliana Gil Melgaço¹, Andréa Marques Vieira da Silva¹, Marcelo Ribeiro-Alves¹, Thyago Leal Calvo¹, Luciana Neves Tubarão¹, Jane da Silva¹, Camilla Bayma Fernandes¹, Alessandro Fonseca de Souza¹, Amanda Torrentes de Carvalho³, Elyzabeth Avvad-Portari¹, Letícia da Cunha Guida¹, Leonardo Gomes¹, Maria Elisabeth Lopes Moreira¹, Ana Paula Dinis Ano Bom¹, Patrícia Cristina da Costa Neves¹, Sotiris Missailidis¹, Zilton Vasconcelos¹, Alexandre Urban Borbely², Milton Ozório Moraes¹

Affiliations

¹ Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.
² Federal University of Alagoas, Maceió, Brazil.
³ Federal Fluminense University, Niterói, Brazil.

Abstract

Zika virus (ZIKV) infections during pregnancy can result in Congenital Zika Syndrome (CZS), a range of severe neurological outcomes in fetuses that primarily occur during early gestational stages possibly due to placental damage. Although some placentas can maintain ZIKV persistence for weeks or months after the initial infection and diagnosis, the impact of this viral persistence is still unknown. Here, we aimed to investigate the immunological repercussion of ZIKV persistence in term placentas. As such, term placentas from 64 pregnant women diagnosed with Zika in different gestational periods were analyzed by ZIKV RT-qPCR, examination of decidua and placental villous histopathology, and expression of inflammation-related genes and IFNL1-4. Subsequently, we explored primary cultures of term decidual Extravillous Trophoblasts (EVTs) and Term Chorionic Villi (TCV) explants, as in vitro models to access the immunological consequences of placental ZIKV infection. Placenta from CZS cases presented low IFNL1-4 expression, evidencing the critical protective role of theses cytokines in the clinical outcome. Term placentas cleared for ZIKV showed increased levels of IFNL1, 3, and 4, whether viral persistence was related with a proinflammatory profile. Conversely, upon ZIKV persistence placentas with decidual inflammation showed high IFNL1-4 levels. In vitro experiments showed that term EVTs are more permissive, and secreted higher levels of IFN-α2 and IFN-λ1 compared to TCV explants. The results suggest that, upon ZIKV persistence, the maternal-skewed decidua contributes to placental inflammatory and antiviral signature, through chronic deciduitis and IFNL upregulation. Although further studies are needed to elucidate the mechanisms underlying the decidual responses against ZIKV. Hence, this study presents unique insights and valuable in vitro models for evaluating the immunological landscape of placentas upon ZIKV persistence.

Keywords: Decidua; Inflammation; Placenta; Type III interferon; Zika virus persistence.