{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T12:46:31Z","timestamp":1790167591385,"version":"4.1.0"},"reference-count":51,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,2,1]],"date-time":"2021-02-01T00:00:00Z","timestamp":1612137600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002367","name":"Chinese Academy of Sciences","doi-asserted-by":"publisher","award":["153211KYSB20160001"],"award-info":[{"award-number":["153211KYSB20160001"]}],"id":[{"id":"10.13039\/501100002367","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:p><jats:italic>Orthobunyaviruses<\/jats:italic> are a group of viruses with significant public and veterinary health importance. These viruses are mainly transmitted through mosquito-, midge-, and tick-vectors, and are endemic to various regions of the world. Ebinur Lake virus (EBIV), a newly identified member of <jats:italic>Orthobunyavirus<\/jats:italic>, was isolated from <jats:italic>Culex<\/jats:italic> mosquitoes in Northwest China. In the present study, we aimed to characterize the pathogenesis and host immune responses of EBIV in BALB\/c mice, as an animal model. Herein, we determined that BALB\/c mice are highly susceptible to EBIV infection. The infected mice exhibited evident clinical signs including weight loss, mild encephalitis, and death. High mortality of mice was observed even with inoculation of one plaque-forming unit (PFU) of EBIV, and the infected mice succumbed to death within 5\u20139 days. After EBIV challenge, rapid viremic dissemination was detected in the peripheral tissues and the central nervous system, with prominent histopathologic changes observed in liver, spleen, thymus, and brain. Blood constituents\u2019 analysis of EBIV infected mice exhibited leukopenia, thrombocytopenia, and significantly elevated ALT, LDH-L, and CK. Further, EBIV infection induced obvious cytokines changes in serum, spleen, and brain in mice. Collectively, our data describe the first study that systematically examines the pathogenesis of EBIV and induced immune response in an immunocompetent standard mouse model, expanding our knowledge of this virus, which may pose a threat to One Health.<\/jats:p>","DOI":"10.3389\/fmicb.2020.625661","type":"journal-article","created":{"date-parts":[[2021,2,1]],"date-time":"2021-02-01T04:58:57Z","timestamp":1612155537000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":17,"title":["Pathogenesis and Immune Response of Ebinur Lake Virus: A Newly Identified Orthobunyavirus That Exhibited Strong Virulence in Mice"],"prefix":"10.3389","volume":"11","author":[{"given":"Lu","family":"Zhao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huanle","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doudou","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiannan","family":"Dong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Mwaliko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evans","family":"Atoni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raphael","family":"Nyaruaba","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiangling","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guilin","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis","family":"Bente","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiming","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han","family":"Xia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,2,1]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"714","DOI":"10.4269\/ajtmh.2010.10-0116","article-title":"Guaroa virus infection among humans in Bolivia and Peru","volume":"83","author":"Aguilar","year":"2010","journal-title":"Am. 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Public Health"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/978-1-4899-1364-7_1","article-title":"History, classification, and taxonomy of viruses in the family Bunyaviridae","volume-title":"The Bunyaviridae. The Viruses.","author":"Calisher","year":"1996"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"117","DOI":"10.4269\/ajtmh.1988.39.117","article-title":"Human infections with Tensaw virus in South Florida: evidence that Tensaw virus subtypes stimulate the production of antibodies reactive with closely related Bunyamwera serogroup viruses","volume":"39","author":"Calisher","year":"1988","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref7","doi-asserted-by":"publisher","first-page":"2621","DOI":"10.1007\/s00705-014-2123-2","article-title":"Caraparu virus induces damage and alterations in antioxidant defenses in the liver of BALB\/c mice after subcutaneous infection","volume":"159","author":"Camini","year":"2014","journal-title":"Arch. Virol."},{"key":"ref8","doi-asserted-by":"publisher","first-page":"20160167","DOI":"10.1098\/rstb.2016.0167","article-title":"One health, emerging infectious diseases and wildlife: two decades of progress?","volume":"372","author":"Cunningham","year":"2017","journal-title":"Philos. Trans. R. Soc. B Biol. Sci."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"e01476","DOI":"10.1128\/mBio.01476-14","article-title":"Viral pathogen-associated molecular patterns regulate blood-brain barrier integrity via competing innate cytokine signals","volume":"5","author":"Daniels","year":"2014","journal-title":"mBio"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"1433","DOI":"10.1111\/tbed.13499","article-title":"Identification of animal hosts of Fort Sherman virus, a new world zoonotic Orthobunyavirus","volume":"67","author":"de Oliveira Filho","year":"2020","journal-title":"Transbound. Emerg. Dis."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"1163","DOI":"10.1093\/brain\/awq048","article-title":"A 10-year follow-up of hippocampal volume on magnetic resonance imaging in early dementia and cognitive decline","volume":"133","author":"Den Heijer","year":"2010","journal-title":"Brain"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"69","DOI":"10.3389\/fvets.2018.00069","article-title":"A review of Bunyamwera, Batai, and Ngari viruses: understudied Orthobunyaviruses with potential one health implications","volume":"5","author":"Dutuze","year":"2018","journal-title":"Front. Vet. Sci."},{"key":"ref13","doi-asserted-by":"publisher","first-page":"794","DOI":"10.3390\/v11090794","article-title":"Throw out the map: neuropathogenesis of the globally expanding California serogroup of orthobunyaviruses","volume":"11","author":"Evans","year":"2019","journal-title":"Viruses"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1016\/j.it.2018.02.007","article-title":"Origin and immunological functions of spleen stromal cells","volume":"39","author":"Golub","year":"2018","journal-title":"Trends Immunol."},{"key":"ref16","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1016\/j.cois.2017.05.004","article-title":"Mosquito-specific and mosquito-borne viruses: evolution, infection, and host defense","volume":"22","author":"Halbach","year":"2017","journal-title":"Curr. Opin. Insect Sci."},{"key":"ref17","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1016\/j.biologicals.2011.02.004","article-title":"Development of inactivated trivalent vaccine for the teratogenic Aino, Akabane and Chuzan viruses","volume":"39","author":"Kim","year":"2011","journal-title":"Biologicals"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"785","DOI":"10.3389\/fendo.2019.00785","article-title":"Expression of EGFR in pituitary corticotroph adenomas and its relationship with tumor behavior","volume":"10","author":"Liu","year":"2019","journal-title":"Front. 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Immunol."},{"key":"ref15","volume-title":"Guide for the care and use of laboratory animals. 8th Edn.","year":"2011"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1080\/20477724.2019.1678939","article-title":"Arboviruses in the East African community partner states: a review of medically important mosquito-borne Arboviruses","volume":"113","author":"Nyaruaba","year":"2019","journal-title":"Pathog. Glob. Health"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1093\/infdis\/131.2.119","article-title":"Role of macrophages in Wesselsbron and Germiston virus infections of mice","volume":"131","author":"Olson","year":"1975","journal-title":"J. Infect. Dis."},{"key":"ref24","doi-asserted-by":"publisher","first-page":"10660","DOI":"10.1073\/pnas.1702914114","article-title":"Cell cycle-targeting microRNAs promote differentiation by enforcing cell-cycle exit","volume":"114","author":"Otto","year":"2017","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"ref25","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1016\/j.meegid.2013.08.015","article-title":"Molecular characterization of the African Orthobunyavirus Ilesha virus","volume":"20","author":"Pachler","year":"2013","journal-title":"Infect. Genet. Evol."},{"key":"ref26","doi-asserted-by":"publisher","first-page":"1110","DOI":"10.3201\/eid2506.181661","article-title":"Novel Orthobunyavirus causing severe kidney disease in broiler chickens, Malaysia, 2014-2017","volume":"25","author":"Palya","year":"2019","journal-title":"Emerg. Infect. 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Biol."},{"key":"ref30","doi-asserted-by":"publisher","first-page":"1165","DOI":"10.1016\/j.biocel.2013.03.010","article-title":"Crossing the wall: the opening of endothelial cell junctions during infectious diseases","volume":"45","author":"Razakandrainibe","year":"2013","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref31","doi-asserted-by":"publisher","first-page":"5586","DOI":"10.1128\/JVI.01821-12","article-title":"Ovine fetal immune response to Cache valley virus infection","volume":"87","author":"Rodrigues Hoffmann","year":"2013","journal-title":"J. Virol."},{"key":"ref32","doi-asserted-by":"publisher","first-page":"2258","DOI":"10.1099\/jgv.0.000899","article-title":"Characterization of five unclassified orthobunyaviruses (Bunyaviridae) from Africa and the Americas","volume":"98","author":"Rogers","year":"2017","journal-title":"J. Gen. Virol."},{"key":"ref33","doi-asserted-by":"publisher","first-page":"411","DOI":"10.3961\/jpmph.17.097","article-title":"One health perspectives on emerging public health threats","volume":"50","author":"Ryu","year":"2017","journal-title":"J. Prev. Med. 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Dis."},{"key":"ref37","doi-asserted-by":"publisher","first-page":"642","DOI":"10.3201\/eid2304.160944","article-title":"Design strategies for efficient arbovirus surveillance","volume":"23","author":"Scarpino","year":"2017","journal-title":"Emerg. Infect. Dis."},{"key":"ref38","doi-asserted-by":"publisher","first-page":"762","DOI":"10.1128\/IAI.2.6.762-766.1970","article-title":"Experimental infection of monkeys with Bunyamwera and Germiston viruses","volume":"2","author":"Schwartz","year":"1970","journal-title":"Infect. Immun."},{"key":"ref39","first-page":"346","article-title":"Zika virus transmission to mouse ear by mosquito bite: a laboratory model that replicates the natural transmission process","volume-title":"Parasit. Vectors","author":"Secundino","year":"2017"},{"key":"ref40","doi-asserted-by":"publisher","first-page":"5987","DOI":"10.3390\/v7112918","article-title":"Genetic and phylogenetic characterization of tataguine and Witwatersrand viruses and other orthobunyaviruses of the anopheles a, Capim, Guam\u00e1, Koongol, Mapputta, Tete, and Turlock Serogroups","volume":"7","author":"Shchetinin","year":"2015","journal-title":"Viruses"},{"key":"ref41","doi-asserted-by":"publisher","first-page":"539","DOI":"10.1038\/nature20167","article-title":"Redefining the invertebrate RNA virosphere","volume":"540","author":"Shi","year":"2016","journal-title":"Nature"},{"key":"ref42","doi-asserted-by":"publisher","first-page":"581","DOI":"10.1139\/cjm-2017-0514","article-title":"Vector competence of certain Culex and Aedes mosquitoes for the Chittoor virus, the Indian variant of the Batai virus","volume":"64","author":"Sudeep","year":"2018","journal-title":"Can. J. Microbiol."},{"key":"ref43","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1186\/s13071-018-3045-8","article-title":"Mosquitoes (Diptera: Culicidae) and mosquito-borne diseases in Mali, West Africa","volume":"11","author":"Tandina","year":"2018","journal-title":"Parasit. Vectors"},{"key":"ref44","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1016\/j.vetmic.2009.04.032","article-title":"Infection by Bunyamwera virus (Orthobunyavirus) in free ranging birds of Cordoba city (Argentina)","volume":"139","author":"Tauro","year":"2009","journal-title":"Vet. Microbiol."},{"key":"ref45","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1016\/j.virol.2008.11.047","article-title":"West Nile virus infection modulates human brain microvascular endothelial cells tight junction proteins and cell adhesion molecules: transmigration across the in vitro blood-brain barrier","volume":"385","author":"Verma","year":"2009","journal-title":"Virology"},{"key":"ref46","doi-asserted-by":"publisher","first-page":"e40380","DOI":"10.1371\/journal.pone.0040380","article-title":"Schmallenberg virus infection of adult type I interferon receptor Knock-out mice","volume":"7","author":"Wernike","year":"2012","journal-title":"PLoS One"},{"key":"ref47","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1186\/s12974-017-0836-3","article-title":"Lymphocytes have a role in protection, but not in pathogenesis, during La Crosse virus infection in mice","volume":"14","author":"Winkler","year":"2017","journal-title":"J. Neuroinflammation"},{"key":"ref48","doi-asserted-by":"publisher","first-page":"3111","DOI":"10.3389\/fmicb.2019.03111","article-title":"Characterization of Ebinur Lake virus and its human Seroprevalence at the China-Kazakhstan border","volume":"10","author":"Xia","year":"2020","journal-title":"Front. Microbiol."},{"key":"ref49","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1007\/s12250-018-0002-9","article-title":"Mosquito-associated viruses in China","volume":"33","author":"Xia","year":"2018","journal-title":"Virol. 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