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

• Published in: Viruses 2023-01, Vol.15 (2), p.320
• Main Authors: Branco, Anna Cláudia Calvielli Castelo, De Oliveira, Emily Araujo, Pereira, Nátalli 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, Rondó, Patrícia Helen Carvalho, Avvad-Portari, Elyzabeth, De Vasconcelos, Zilton Farias Meira, Duarte, Alberto José da Silva, Azamor, Tamiris, Sato, Maria Notomi
• Format: Article
• Language: English
• Subjects: Analysis; Antiviral Agents; antiviral factors; Body mass index; Body weight; Brazil - epidemiology; Cohort Studies; Complications and side effects; Decidua; Female; Fetuses; Health aspects; Humans; Immune response; Infant, Newborn; Interferon regulatory factor 3; Interferon Type I; Maternal-fetal exchange; Microcephaly; Microencephaly; Neonates; Obesity; Placenta; Pregnancy; Pregnant Women; Public health; Signal transduction; Womens health; Zika Virus; Zika Virus Infection - complications
• ISSN: 1999-4915; 1999-4915
• DOI: 10.3390/v15020320

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 (São 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.