Obesity Induces an Impaired Placental Antiviral Immune Response in Pregnant Women Infected with Zika Virus

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Branco, Anna Claudia Calvielli Castelo ; De Oliveira, Emily Araujo ; Pereira, Natalli Zanete ; Alberca, Ricardo Wesley ; Duarte-Neto, Amaro Nunes ; Da Silva, Luiz Fernando Ferraz ; Luiz, Fernanda Guedes ; Pereira, Naiura Vieira ; Sotto, Mirian Nacagami ; Dejani, Naiara Naiana ; Rondo, Patricia Helen Carvalho ; Avvad-Portari, Elyzabeth ; De Vasconcelos, Zilton Farias Meira ; Duarte, Alberto Jose da Silva ; Azamor, Tamiris ; Sato, Maria Notomi

• Document type: Journal article
• Source: Viruses-Basel; v. 15, n. 2, p. 15-pg., 2023-02-01.

Abstract

Obesity is increasing in incidence worldwide, especially in women, which can affect the outcome of pregnancy. During this period, viral infections represent a risk to the mother, the placental unit, and the fetus. The Zika virus (ZIKV) outbreak in Brazil has been the cause of congenital Zika syndrome (CZS), with devastating consequences such as microcephaly in newborns. Herein, we analyzed the impact of maternal overweight/obesity on the antiviral factors' expression in the placental tissue of Zika-infected mothers. We accessed placentas from women with and without obesity from 34 public health units (Sao Paulo) and from Zika-infected mothers with and without obesity from the Clinical Cohort Study of ZIKV pregnant women (Rio de Janeiro, Brazil). We first verified that obesity, without infection, did not alter the constitutive transcriptional expression of antiviral factors or IFN type I/III expression. Interestingly, obesity, when associated with ZIKV infection, showed a decreased transcriptional expression of RIG-I and IFIH1 (MDA-5 protein precursor gene). At the protein level, we also verified a decreased RIG-I and IRF-3 expression in the decidual placenta from the Zika-infected obese group, regardless of microcephaly. This finding shows, for the first time, that obesity associated with ZIKV infection leads to an impaired type I IFN downstream signaling pathway in the maternal-fetal interface. (AU)

• FAPESP's process: 15/03333-6 - The relationship between maternal adiposity and adiposity of the offspring in the fetal, neonatal and infant periods: a prospective population-based study
• Grantee: Patricia Helen de Carvalho Rondó
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 19/26928-6 - Phenotypic and functional evaluation of Regulatory T cells in gestational obesity
• Grantee: Emily Araujo de Oliveira
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 19/25119-7 - Maternal-fetal interface: immunopathogenesis and vaccinal intervention in viral infections
• Grantee: Maria Notomi Sato
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 17/07143-2 - An immunological approach to the relationship between maternal and fetal adiposity in fetal, neonatal and infant periods
• Grantee: Naiara Naiana Dejani
• Support Opportunities: Scholarships in Brazil - Post-Doctoral