Work

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

Year: 2025

Type: article

Abstract: Oropouche fever is a debilitating disease caused by Oropouche virus (OROV), an arthropod-borne member of the Peribunyaviridae family. Despite its public health significance, the molecular mechanisms driving OROV pathogenesis remain poorly understood. In other bunyaviruses, the nonstructural NSs protein encoded by the small (S) genome segment acts as a major virulence factor. In this study, infection with the OROV MD023 strain led to nuclear accumulation of NSs and redistribution of nucleophosmin 1 (NPM1) from the nucleolus. OROV infection suppressed nascent RNA synthesis and resulted in decreased levels of the RNA polymerase II (RNAP II) subunit RPB1, along with reduced phosphorylation of its C-terminal domain (CTD) at serine 2 and serine 5 residues. When expressed from a recombinant Rift Valley fever virus MP-12 strain, OROV NSs colocalized with NPM1 and contributed to its nucleolar redistribution. Furthermore, expression of OROV NSs induced a marked reduction in the hyperphosphorylated RNAP IIo form, which was largely restored upon treatment with the proteasome inhibitor MG132. These findings suggest that OROV NSs promote RNAP II degradation and suppress host transcription, underscoring its potential role in modulating host responses during infection. IMPORTANCE: 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.

Source: Journal of Virology

DOI: 10.1128/jvi.01176-25

Authors: Eduardo Jurado-Cobena, Cigdem Alkan, Tetsuro Ikegami

Institution: The University of Texas Medical Branch at Galveston

Language: English

Topic: Viral Infections and Vectors

Subfield: Infectious Diseases

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: diamond

Funders: Sealy Institute for Vaccine Sciences, University of Texas Medical Branch, National Institute of Allergy and Infectious Diseases