Oropouche virus NSs protein suppresses host transcription by targeting the RNA polymerase II RPB1 protein

Oropouche fever is a viral disease characterized by fever, headaches, and body aches, affecting thousands of people in tropical regions. The Oropouche virus (OROV) has caused and continues to cause medium to large-scale outbreaks, highlighting the urgent need to better understand its basic biology. This study focused on the viral NSs protein, which modulates host antiviral responses. Our findings demonstrate that NSs disrupt RNA polymerase II, a key enzyme in host gene expression, by reducing its activity and stability. Additionally, OROV infection alters the nucleolus, a critical center for cellular stress responses and ribosome biogenesis. These disruptions suggest that OROV suppresses host transcription and nucleolar function, thereby impairing the cellular antiviral response. Understanding these mechanisms provides new insights into host-virus interactions and viral strategies for modulating host cell responses.