{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T23:39:28Z","timestamp":1783640368050,"version":"3.55.0"},"reference-count":61,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T00:00:00Z","timestamp":1761609600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Oropouche virus (OROV) is an emerging arbovirus responsible for Oropouche fever, also known as sloth fever, a febrile illness that can lead to recurrent outbreaks in affected regions. Endemic to parts of South and Central America, OROV is primarily transmitted by biting midges (Culicoides paraensis), although mounting evidence implicates mosquitoes, particularly the Culex and Aedes species, as additional vectors. Recent ecological disturbances\u2014such as deforestation, urbanization, and climate change\u2014have driven significant shifts in vector population dynamics, contributing to the expanded geographic range and increased transmission of OROV. Notably, recent reports of OROV infections among American and European travelers to Cuba highlight the virus\u2019s growing potential for international dissemination and underscore its significance as a global health concern. OROV is an enveloped orthobunyavirus within the Peribunyaviridae family, possessing a tripartite, single-stranded, negative-sense RNA genome composed of the S (small), M (medium), and L (large) segments. These segments encode the nucleocapsid (N) protein, glycoproteins (Gn and Gc), and RNA-dependent RNA polymerase, respectively. Despite increasing incidence and potential for global spread, no licensed vaccines or antiviral therapies currently exist, and effective diagnostic tools remain limited. Furthermore, although human-to-human transmission has not been observed, the absence of robust surveillance systems complicates timely outbreak detection and response. In this study, we present a comprehensive molecular characterization of OROV\u2019s major structural proteins, with an emphasis on structural modeling and epitope prediction. By integrating bioinformatics approaches with available structural data, we identify key antigenic regions that could serve as targets for the development of serological diagnostics and vaccine candidates. Our findings contribute critical insights into the molecular virology of OROV and provide a foundational framework for future efforts aimed at the prevention, diagnosis, and control of this neglected tropical pathogen. These advancements are essential for mitigating the impact of OROV in endemic regions and reducing the risk of global emergence.<\/jats:p>","DOI":"10.3390\/v17111434","type":"journal-article","created":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T17:02:01Z","timestamp":1761670921000},"page":"1434","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Charting the Proteins of Oropouche Virus"],"prefix":"10.3390","volume":"17","author":[{"given":"Sunil","family":"Thomas","sequence":"first","affiliation":[{"name":"Lankenau Institute for Medical Research, Wynnewood, PA 19096, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"574","DOI":"10.4269\/ajtmh.1961.10.574","article-title":"Oropouche virus: A new human disease agent from Trinidad, West Indies","volume":"10","author":"Anderson","year":"1961","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1038\/s41541-022-00456-2","article-title":"Baseline mapping of Oropouche virology, epidemiology, therapeutics, and vaccine research and development","volume":"7","author":"Files","year":"2022","journal-title":"NPJ Vaccines"},{"key":"ref_3","first-page":"213","article-title":"An outbreak of Oropouche virus disease in the vicinity of Santarem, Para, Brazil","volume":"27","author":"Pinheiro","year":"1976","journal-title":"Tropenmed. Parasitol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"100456","DOI":"10.1016\/j.ijregi.2024.100456","article-title":"Oropouche virus: A re-emerging arbovirus of clinical significance","volume":"13","author":"Desai","year":"2024","journal-title":"IJID Reg."},{"key":"ref_5","unstructured":"Centers for Disease Control and Prevention\/CDC (2025, August 20). Countries and Territories with Recent or Previous Oropouche Virus Transmission, Available online: https:\/\/www.cdc.gov\/oropouche\/data-maps\/countries-and-territories-at-risk-for-oropouche.html."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"769","DOI":"10.15585\/mmwr.mm7335e1","article-title":"Oropouche Virus Disease Among U.S. Travelers\u2014United States","volume":"73","author":"Morrison","year":"2024","journal-title":"MMWR Morb. Mortal. Wkly. Rep."},{"key":"ref_7","unstructured":"Pan American Health Organization\/PAHO (2025, August 24). PAHO Publishes New Update on Oropouche Fever in the Americas. Available online: https:\/\/www.paho.org\/en\/news\/14-8-2025-paho-publishes-new-update-oropouche-fever-americas."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.jcv.2008.11.006","article-title":"Oropouche fever epidemic in Northern Brazil: Epidemiology and molecular characterization of isolates","volume":"44","author":"Vasconcelos","year":"2009","journal-title":"J. Clin. Virol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"380","DOI":"10.3201\/eid2502.181189","article-title":"Oropouche virus-associated aseptic meningoencephalitis, Southeastern Brazil","volume":"25","author":"Vernal","year":"2019","journal-title":"Emerg. Infect. Dis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1007\/s13365-021-00987-9","article-title":"Neurological disease caused by Oropouche virus in northern Brazil: Should it be included in the scope of clinical neurological diseases?","volume":"27","author":"Chiang","year":"2021","journal-title":"J. Neurovirol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2439521","DOI":"10.1080\/21505594.2024.2439521","article-title":"Oropouche virus: Understanding \u201csloth fever\u201d disease dynamics and novel intervention strategies against this emerging neglected tropical disease","volume":"15","author":"Cain","year":"2024","journal-title":"Virulence"},{"key":"ref_12","first-page":"2616","article-title":"Generation of Recombinant Oropouche Viruses Lacking the Nonstructural Protein NSm or NSs","volume":"90","author":"Acrani","year":"2015","journal-title":"J. Virol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Sakkas, H., Bozidis, P., Franks, A., and Papadopoulou, C. (2018). Oropouche fever: A review. Viruses, 10.","DOI":"10.3390\/v10040175"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.micinf.2017.11.013","article-title":"Oropouche fever, an emergent disease from the Americas","volume":"20","author":"Escobar","year":"2018","journal-title":"Microbes Infect."},{"key":"ref_15","first-page":"100406","article-title":"Re-emergence of Oropouche virus as a novel global threat","volume":"8","author":"Salvato","year":"2025","journal-title":"Curr. Res. Microb. Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"172","DOI":"10.4269\/ajtmh.1981.30.172","article-title":"Oropouche virus. IV. Laboratory transmission by Culicoides paraensis","volume":"30","author":"Pinheiro","year":"1981","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1251","DOI":"10.1126\/science.6800036","article-title":"Transmission of Oropouche virus from man to hamster by the midge Culicoides paraensis","volume":"215","author":"Pinheiro","year":"1982","journal-title":"Science"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"de Mendon\u00e7a, S.F., Rocha, M.N., Ferreira, F.V., Leite, T.H.J.F., Amadou, S.C.G., Sucupira, P.H.F., Marques, J.T., Ferreira, A.G.A., and Moreira, L.A. (2021). Evaluation of Aedes aegypti, Aedes albopictus, and Culex quinquefasciatus mosquitoes competence to Oropouche virus infection. Viruses, 13.","DOI":"10.3390\/v13050755"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e01127-19","DOI":"10.1128\/JVI.01127-19","article-title":"Evolutionary Dynamics of Oropouche Virus in South America","volume":"94","author":"Gutierrez","year":"2020","journal-title":"J. Virol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e2204706119","DOI":"10.1073\/pnas.2204706119","article-title":"Oropouche orthobunyavirus infection is mediated by the cellular host factor Lrp1","volume":"119","author":"Schwarz","year":"2022","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_21","unstructured":"(2024, August 08). National Center for Biological Information, Available online: https:\/\/www.ncbi.nlm.nih.gov\/protein\/."},{"key":"ref_22","unstructured":"National Center for Biological Information (2024, August 12). Conserved Domains, Available online: https:\/\/www.ncbi.nlm.nih.gov\/Structure\/cdd\/wrpsb.cgi."},{"key":"ref_23","unstructured":"(2025, October 07). PTMGPT2: Post-Translational Modification Prediction via Prompt-Based Fine-Tuning of a GPT-2 Model. Available online: https:\/\/nsclbio.jbnu.ac.kr\/tools\/ptmgpt2."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"6699","DOI":"10.1038\/s41467-024-51071-9","article-title":"Post-translational modification prediction via prompt-based fine-tuning of a GPT-2 model","volume":"15","author":"Shrestha","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3856","DOI":"10.1093\/nar\/gkg552","article-title":"Building protein diagrams on the web with the residue-based diagram editor RbDe","volume":"31","author":"Skrabanek","year":"2003","journal-title":"Nucleic Acids Res."},{"key":"ref_26","unstructured":"Protter (2024, August 19). Interactive Protein Feature Visualization. Available online: https:\/\/wlab.ethz.ch\/protter\/start\/."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"884","DOI":"10.1093\/bioinformatics\/btt607","article-title":"Protter: Interactive protein feature visualization and integration with experimental proteomic data","volume":"30","author":"Omasits","year":"2014","journal-title":"Bioinformatics"},{"key":"ref_28","unstructured":"Phobius (2024, August 13). A Combined Transmembrane Topology and Signal Peptide Predictor. Available online: https:\/\/phobius.sbc.su.se\/."},{"key":"ref_29","first-page":"1","article-title":"Mapping the accessory proteins (Orfs) of Severe Acute Respiratory Syndrome Coronavirus 2","volume":"3","author":"Thomas","year":"2023","journal-title":"Re:GEN Open"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Thomas, S. (2024). Plotting the major proteins of borealpox virus. Front. Virol., 4.","DOI":"10.3389\/fviro.2024.1451810"},{"key":"ref_31","unstructured":"(2024, August 12). Alphafold2. Available online: https:\/\/colab.research.google.com\/github\/sokrypton\/ColabFold\/blob\/main\/AlphaFold2.ipynb."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1038\/s41586-021-03819-2","article-title":"Highly accurate protein structure prediction with AlphaFold","volume":"596","author":"Jumper","year":"2021","journal-title":"Nature"},{"key":"ref_33","unstructured":"Phyre2 (2024, August 15). Protein Fold Recognition Server. Available online: http:\/\/www.sbg.bio.ic.ac.uk\/phyre2."},{"key":"ref_34","unstructured":"I-TASSER (2024, November 12). Protein Structure and Function Predictions. Available online: https:\/\/zhanggroup.org\/I-TASSER\/."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1016\/j.jmb.2015.09.024","article-title":"ResQ: An approach to unified estimation of B-factor and residue-specific error in protein structure prediction","volume":"428","author":"Yang","year":"2016","journal-title":"J. Mol. Biol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"5.8.1","DOI":"10.1002\/0471250953.bi0508s52","article-title":"Protein Structure and Function Prediction Using I-TASSER","volume":"52","author":"Yang","year":"2015","journal-title":"Curr. Protoc. Bioinform."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2302","DOI":"10.1093\/nar\/gki524","article-title":"TM-align: A protein structure alignment algorithm based on the TM-score","volume":"33","author":"Zhang","year":"2005","journal-title":"Nucleic Acids Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1007\/978-1-61779-588-6_10","article-title":"Methods of protein structure comparison","volume":"857","author":"Kufareva","year":"2012","journal-title":"Methods Mol. Biol."},{"key":"ref_39","unstructured":"(2024, September 05). IEDB Analysis Resource. Available online: http:\/\/tools.iedb.org\/main\/."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"W24","DOI":"10.1093\/nar\/gkx346","article-title":"BepiPred-2.0: Improving sequence-based B-cell epitope prediction using conformational epitopes","volume":"45","author":"Jespersen","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"ref_41","unstructured":"Department of Health Technology (2024, October 22). NetSurfP-3.0. Protein Secondary Structure and Relative Solvent Accessibility. Available online: https:\/\/services.healthtech.dtu.dk\/services\/NetSurfP-3.0\/."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"W510","DOI":"10.1093\/nar\/gkac439","article-title":"NetSurfP-3.0: Accurate and fast prediction of protein structural features by protein language models and deep learning","volume":"50","author":"Kiehl","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"ref_43","unstructured":"(2025, September 11). UniProt. Available online: https:\/\/www.uniprot.org\/align."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"199318","DOI":"10.1016\/j.virusres.2024.199318","article-title":"Oropouche virus: A neglected global arboviral threat","volume":"341","author":"Zhang","year":"2024","journal-title":"Virus Res."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Endalew, A.D., Faburay, B., Wilson, W.C., and Richt, J.A. (2019). Schmallenberg disease\u2014A newly emerged culicoides-borne viral disease of ruminants. Viruses, 11.","DOI":"10.3390\/v11111065"},{"key":"ref_46","first-page":"15","article-title":"Epidemia de v\u00edrus Oropouche em Bel\u00e9m","volume":"12","author":"Pinheiro","year":"1962","journal-title":"Rev. Serv. Esp. Sa\u00fade P\u00fabl."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"937","DOI":"10.3201\/eid2405.ET2405","article-title":"Etymologia: Oropouche virus","volume":"24","author":"Henry","year":"2018","journal-title":"Emerg. Infect. Dis."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"100904","DOI":"10.1016\/S2666-5247(24)00136-8","article-title":"Oropouche fever outbreak in Brazil: An emerging concern in Latin America","volume":"3","author":"Sah","year":"2024","journal-title":"Lancet Microbe"},{"key":"ref_49","unstructured":"World Health Organization (2024, August 15). Oropouche Virus Disease\u2014Cuba. Available online: https:\/\/www.who.int\/emergencies\/disease-outbreak-news\/item\/2024-DON521#:~:text=Oropouche%20virus%20disease%20is%20an,to%2Dhuman%20Oropouche%20virus%20transmission."},{"key":"ref_50","unstructured":"European Centre for Disease Prevention and Control (2024). Oropouche Virus Disease Cases Imported into the European Union\u20149 August 2024, ECDC."},{"key":"ref_51","unstructured":"World Health Organization (2024, August 15). Oropouche Virus Disease. Available online: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/oropouche-virus-disease#:~:text=In%202024%20concerns%20arose%20about,that%20requires%20further%20investigation%20and."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"6718083","DOI":"10.1155\/2018\/6718083","article-title":"Immunoinformatics approach for epitope-based peptide vaccine design and active site prediction against polyprotein of emerging Oropouche virus","volume":"2018","author":"Adhikari","year":"2018","journal-title":"J. Immunol. Res."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Stubbs, S.H., Cornejo Pontelli, M., Mishra, N., Zhou, C., de Paula Souza, J., Mendes Viana, R.M., Lipkin, W.I., Knipe, D.M., Arruda, E., and Whelan, S.P.J. (2021). Vesicular stomatitis virus chimeras expressing the Oropouche virus glycoproteins elicit protective immune responses in mice. mBio, 12.","DOI":"10.1128\/mBio.00463-21"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1080\/14760584.2017.1306441","article-title":"Influence of protein fold stability on immunogenicity and its implications for vaccine design","volume":"16","author":"Scheiblhofer","year":"2017","journal-title":"Expert Rev. Vaccines"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.trivac.2016.04.003","article-title":"B-cell epitope mapping for the design of vaccines and effective diagnostics","volume":"5","author":"Ahmad","year":"2016","journal-title":"Trials Vaccinol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"7215","DOI":"10.1038\/s41467-025-60526-6","article-title":"Characterizing and engineering post-translational modifications with high-throughput cell-free expression","volume":"16","author":"Wong","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Kumar, R., Mehta, D., Mishra, N., Nayak, D., and Sunil, S. (2020). Role of host-mediated post-translational modifications (PTMs) in RNA virus pathogenesis. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22010323"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1111\/j.1365-3024.2009.01099.x","article-title":"Antigenic protein modifications in Ehrlichia","volume":"31","author":"Thomas","year":"2009","journal-title":"Parasite Immunol."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Thomas, S., Thirumalapura, N.R., Crocquet-Valdes, P.A., Luxon, B.A., and Walker, D.H. (2011). Structure-based vaccines provide protection in a mouse model of ehrlichiosis. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0027981"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"eadx9405","DOI":"10.1126\/sciadv.adx9405","article-title":"Oropouche virus efficiently replicates and is immunostimulatory in vivo in nonhuman primate species","volume":"11","author":"Yee","year":"2025","journal-title":"Sci. Adv."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"328","DOI":"10.4269\/ajtmh.15-0679","article-title":"Isolation of Madre de Dios Virus (Orthobunyavirus; Bunyaviridae), an Oropouche virus species reassortant, from a monkey in Venezuela","volume":"95","author":"Navarro","year":"2016","journal-title":"Am. J. Trop. Med. 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