{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T04:59:58Z","timestamp":1785387598798,"version":"3.55.0"},"reference-count":43,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T00:00:00Z","timestamp":1785196800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"EU","award":["No. PE00000007"],"award-info":[{"award-number":["No. PE00000007"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Oropouche virus (OROV), an Orthobunyavirus of the Peribunyaviridae family, is usually transmitted to humans by biting midges, while, to date, cases of human-to-human transmission have not been reported. Although OROV\u2019s 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-\u03b1\/\u03b2 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-\u03b2 expression. Our results demonstrate that the NSs protein mediates a reduction in IFN-\u03b2 promoter activation, hindering RIG-I and IRF-3, therefore acting on multiple steps of the IFN-\u03b2 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-\u03b2 modulation.<\/jats:p>","DOI":"10.3390\/v18080828","type":"journal-article","created":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T07:55:41Z","timestamp":1785225341000},"page":"828","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Oropouche Virus: Comparative Study of Two Strains Reveals Distinct Innate Immunity Modulation"],"prefix":"10.3390","volume":"18","author":[{"given":"Letizia","family":"Rizzo","sequence":"first","affiliation":[{"name":"Department of Medical Biotechnologies, University of Siena, Viale Bracci 16, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Alessandri","sequence":"additional","affiliation":[{"name":"Department of Medical Biotechnologies, University of Siena, Viale Bracci 16, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2287-9258","authenticated-orcid":false,"given":"Gianni","family":"Gori Savellini","sequence":"additional","affiliation":[{"name":"Department of Medical Biotechnologies, University of Siena, Viale Bracci 16, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2379-1082","authenticated-orcid":false,"given":"Sara","family":"Caldrer","sequence":"additional","affiliation":[{"name":"Virology and Emerging Pathogens Unit, Department of Infectious, Tropical Diseases and Microbiology, IRCCS Sacro Cuore Don Calabria Hospital, Negrar di Valpolicella, 37024 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9819-236X","authenticated-orcid":false,"given":"Concetta","family":"Castilletti","sequence":"additional","affiliation":[{"name":"Virology and Emerging Pathogens Unit, Department of Infectious, Tropical Diseases and Microbiology, IRCCS Sacro Cuore Don Calabria Hospital, Negrar di Valpolicella, 37024 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8869-8164","authenticated-orcid":false,"given":"Maria Grazia","family":"Cusi","sequence":"additional","affiliation":[{"name":"Department of Medical Biotechnologies, University of Siena, Viale Bracci 16, 53100 Siena, Italy"},{"name":"Microbiology and Virology Unit, Santa Maria delle Scotte University Hospital, Viale Bracci 16, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1099\/jgv.0.001365","article-title":"ICTV Virus Taxonomy Profile: Peribunyaviridae","volume":"101","author":"Hughes","year":"2020","journal-title":"J. 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