Viruses · Published 2026-07-28 · DOI 10.3390/v18080828
Letizia Rizzo, Giulia Alessandri, Gianni Gori Savellini, Sara Caldrer, Concetta Castilletti, Maria Grazia Cusi
Oropouche virus (OROV), an Orthobunyavirus of the <i>Peribunyaviridae</i> family, is usually transmitted to humans by biting midges, while, to date, cases of human-to-human transmission have not been reported. Although OROV’s clinical manifestation is usually characterized by mild symptoms, cases of Central Nervous System (CNS) infections have been reported. The non-structural protein NSs of many bunyaviruses and phleboviruses acts as a major virulence factor. Previous studies have demonstrated that OROV NSs also behaves as a suppressor of the host IFN-α/β responses. Furthermore, OROV NSs protein promotes cellular RPB1 proteasomal degradation to suppress RNA synthesis. In the present work, we perform a comparative study on two OROV strains (BeAn19991 and IRCCS-SCDC_1/2024) to further characterize the molecular mechanisms by which OROV NSs inhibits IFN-β expression. Our results demonstrate that the NSs protein mediates a reduction in IFN-β promoter activation, hindering RIG-I and IRF-3, therefore acting on multiple steps of the IFN-β signaling pathway. However, this suppression seems to reside in the blockage of RPB1 rather than a direct effect on those mediators. Moreover, we investigated the behavior of the two virus strains in a human glioblastoma cell line derived from brain (DBTRG.05MG cells) and fibroblasts (MRC-5 cells), observing different replication kinetics, degradation activity towards RPB1, and strength/timing of IFN-β modulation.
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Rizzo, L., Alessandri, G., Savellini, G., et al. (2026). Oropouche Virus: Comparative Study of Two Strains Reveals Distinct Innate Immunity Modulation. Viruses. https://doi.org/10.3390/v18080828