Interference of Oropouche Virus in the Cellular Levels of RNA Polymerase II and STAT2: Implications for Viral Replication and Immune Evasion

• Grant number: 24/22883-6
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: March 01, 2025
• End date: February 28, 2026
• Field of knowledge: Biological Sciences - Microbiology - Biology and Physiology of Microorganisms
• Principal Investigator: Luis Lamberti Pinto da Silva
• Grantee: Maria Eduarda de Siqueira Oliveira e Silva
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

The Oropouche virus (OROV) is an enveloped virus with a genome composed of three RNA segments, encoding four structural proteins (N, RdRp, Gn, and Gc) and two non-structural proteins (NSm and NSs). OROV is the causative agent of Oropouche fever, a febrile illness affecting Brazil and several other countries in South and Central America. Recent cases suggest that viral infection may be associated with neurological damage, fetal malformations, and mortality, underscoring the importance of in-depth studies on the virus and its replication mechanisms. Despite the increasing number of reported cases, the true scale and distribution of the disease remain underestimated. This underreporting stems from the lack of routine testing and the similarity of its clinical manifestations to other common arboviruses in Brazil, complicating accurate diagnosis. Preliminary proteomic analyses conducted in our laboratory indicate that OROV infection specifically alters the expression levels of several cellular proteins, potentially involved in viral replication and antiviral response. Among these are reductions in the levels of RNA polymerase II and STAT2. Based on these observations, this project aims to elucidate the mechanisms used by OROV to reduce the levels of these cellular proteins and identify the viral proteins involved in this process.