The role of innate recognition pathways and type I and III interferons in barrier disruption followed by OROV infection

Author(s)

Stéfanie Primon Muraro

• Document type: Doctoral Thesis
• Press: Campinas, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia
• Defense date: 2024-05-03

Examining board members

José Luiz Proença Módena; Cristina Bonorino; Fabio Trindade Maranhão Costa; Murilo de Carvalho; Rafael Freitas Oliveira Franca

• Advisor: José Luiz Proença Módena

Abstract

The Orthobunyavirus oropoucheense (OROV) is an arbovirus capable of causing epidemics and leads to a febrile illness that can escalate to neurological and hemorrhagic complications in humans. While some studies have shown that OROV infection elicits an immune response reliant on type I interferon production, there is currently a lack of data investigating the potential impact of OROV on pregnancy and the role of this cytokine in the control of fetal and placental infection. For this, we infected pregnant WT, SJL, Ifnar1-/-, IL28Ra-/- and Mavs-/- mice along with human trophoblasts cell lines with OROV. Our findings indicate that OROV infection triggers the development of an antiviral response in trophoblast cell lines, involving the production of type I and III interferons. The study also established a maternal-fetal transmission model by infecting intravenously pregnant dams, on embrionary day 10 resulting in significant differences in outcomes based on the genetic background of the mice. Crosses in which the female has a deletion of Ifnar1 lead to high viral loads in the placenta and fetus, while crosses in which the female has a partial deletion of Ifnar1 allow harboring low viral concentrations, but still capable of reaching the fetus, suggesting a critical role of type I interferon signaling in the pathogenesis of congenital OROV infection. Furthermore, the data also indicates that OROV can traverse the placental barrier regardless of the genetic background of the dam, sire, or fetal genotype. Viral RNA was detected as early as 8 days after infection in fetal tissues, but no infectious virus was found. Surprisingly, the expected protection offered by IFN-type III during OROV infection was not observed, since IL28Ra-/- mice were not more susceptible to OROV infection. These results shed light on the complex interactions between the virus and the host's immune response during placental-fetal transmission of OROV (AU)

• FAPESP's process: 18/13645-3 - The role of innate recognition pathways and type I and III interferons in the rupture of the placental barrier after OROV infection
• Grantee: Stefanie Primon Muraro
• Support Opportunities: Scholarships in Brazil - Doctorate