Evaluation of the role of viral glycoprotein Gc in cross-immunity between different strains of Oropouche virus (OROV)

• Grant number: 24/22655-3
• Support Opportunities: Scholarships in Brazil - Master
• Start date: July 01, 2025
• End date: January 31, 2027
• Field of knowledge: Biological Sciences - Immunology - Applied Immunology
• Principal Investigator: Rafael Freitas de Oliveira Franca
• Grantee: Mayume Martins Santana
• Host Institution: Plataforma de Pesquisa e Medicina Translacional. Fundação Oswaldo Cruz (Fiocruz). Ministério da Saúde (Brasil). Ribeirão Preto , SP, Brazil
• Associated research grant: 24/02373-3 - Application of CRISPR libraries for screening cellular factors associated with arbovirus neuroinfection, AP.R

Abstract

The Oropouche virus is considered a neglected zoonosis, belonging to the family Peribunyaviridae and the genus Orthobunyavirus, being transmitted by arthropods circulating in Central America, South America and the Caribbean. The clinical signs of this disease are similar to other endemic arboviruses in Latin America, such as dengue, chikungunya, Zika and mayaro. Several cases have already been identified in South American countries, such as Bolivia, Brazil, Colombia and Peru. OROV presents single-stranded RNA containing three gene segments called: S segment (small) encoding the nucleocapsid protein N (NS) and non-structural protein (NSs), medium segment (medium) encoding glycoproteins (Gn, Gc and NSm) and large segment (large) L protein encoder and an RNA polymerase. Because the genome is segmented, gene rearrangements may occur resulting in greater genetic diversity. Gc and Gn glycoproteins are characterized as class II membrane fusion glycoproteins, constituted as heterodimers of Gn-Gc designed to cover the virion membrane, having an important role in viral infection. A recent outbreak of Oropouche virus (OROV) in the northern region of Brazil, with more than 8,000 cases reported only in 2024, was associated with the detection of a new viral strain called reassortant or BR2015-2023, consisting of new gene segments (M1L2S2). Thus, the objective of this study is to immunologically characterize the Gc glycoproteins, evaluating their potential to induce cross-immunity among different OROV isolates. Although there are advances in research that seek to understand the pathogen, including the identification of new strains such as the recently found in Brazil, no vaccines are available for the Oropouche virus and no specific antiviral treatments or effective immunizations for the disease. Thus, the project will be able to offer a better understanding of the immunological mechanisms involved in the induction of protective responses with the purpose of mitigating the pathogenic and socioeconomic effects caused by arbovirus on public health. (AU)