Oropouche virus infection and neurological involvement: a hypothesis-generating neuroimmune framework

Oropouche virus (OROV), an emerging orthobunyavirus in the Americas, has historically been associated with self-limited febrile illness in endemic Amazon basin regions. However, recent epidemiological updates from the Pan American Health Organization (PAHO) and World Health Organization (WHO) document a marked increase in case counts and geographic expansion, with over 16,000 confirmed cases reported in 2024 and continued transmission across multiple countries in 2025, including regions where transmission had not been previously recognized. The detection of cases in the Caribbean, Central America, and imported infections in North America and Europe underscores its evolving epidemiological profile and growing global relevance. In parallel with this expansion, neurological involvement-including meningitis and encephalitis-has been reported in a subset of patients. Experimental and ex vivo studies demonstrate neural permissiveness and suggest the capacity for interaction with central nervous system (CNS) tissue. Based on established principles of viral neuroimmunology, a conservative conceptual framework is proposed linking acute neuroimmune activation during OROV infection to potential neurological manifestations. Although long-term neurological sequelae have not been systematically characterized, existing clinical observations and biological mechanisms provide plausibility for further investigation. This framework is intended to generate testable hypotheses and guide prospective studies rather than establish causality.