{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T07:43:44Z","timestamp":1792827824342,"version":"4.5.0"},"reference-count":32,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2024,4,16]],"date-time":"2024-04-16T00:00:00Z","timestamp":1713225600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/doi.org\/10.1128\/ASMCopyrightv2"},{"start":{"date-parts":[[2024,4,16]],"date-time":"2024-04-16T00:00:00Z","timestamp":1713225600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["HHSN272201700041I"],"award-info":[{"award-number":["HHSN272201700041I"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["75N93019D00021"],"award-info":[{"award-number":["75N93019D00021"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI152236"],"award-info":[{"award-number":["AI152236"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"name":"HHS | NIH | NIAID | Division of Intramural Research"},{"DOI":"10.13039\/100000774","name":"DOD | Defense Threat Reduction Agency","doi-asserted-by":"crossref","award":["MCDC2005-005"],"award-info":[{"award-number":["MCDC2005-005"]}],"id":[{"id":"10.13039\/100000774","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Institute for Human Infections and Immunity, University of Texas Medical Branch","award":["Data acquisition grant"],"award-info":[{"award-number":["Data acquisition grant"]}],"id":[{"id":"https:\/\/ror.org\/016tfm930","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2024,4,16]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>Heartland virus (HRTV) is an emerging tick-borne bandavirus that causes a febrile illness of varying severity in humans, with cases reported in eastern and midwestern regions of the United States. No vaccines or approved therapies are available to prevent or treat HRTV disease. Here, we describe the genetic changes, natural history of disease, and pathogenesis of a mouse-adapted HRTV (MA-HRTV) that is uniformly lethal in 7- to 8-week-old AG129 mice at low challenge doses. We used this model to assess the efficacy of the ribonucleoside analog, 4\u2032-fluorouridine (EIDD-2749), and showed that once-daily oral treatment with 3 mg\/kg of drug, initiated after the onset of disease, protects mice against lethal MA-HRTV challenge and reduces viral loads in blood and tissues. Our findings provide insights into HRTV virulence and pathogenesis and support further development of EIDD-2749 as a therapeutic intervention for HRTV disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>IMPORTANCE<\/jats:title>\n                    <jats:p>More than 60 cases of HRTV disease spanning 14 states have been reported to the United States Centers for Disease Control and Prevention. The expanding range of the Lone Star tick that transmits HRTV, the growing population of at-risk persons living in geographic areas where the tick is abundant, and the lack of antiviral treatments or vaccines raise significant public health concerns. Here, we report the development of a new small-animal model of lethal HRTV disease to gain insight into HRTV pathogenesis and the application of this model for the preclinical development of a promising new antiviral drug candidate, EIDD-2749. Our findings shed light on how the virus causes disease and support the continued development of EIDD-2749 as a therapeutic for severe cases of HRTV infection.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/jvi.00132-24","type":"journal-article","created":{"date-parts":[[2024,3,21]],"date-time":"2024-03-21T09:00:35Z","timestamp":1711011635000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":16,"title":["Modeling Heartland virus disease in mice and therapeutic intervention with 4\u2032-fluorouridine"],"prefix":"10.1128","volume":"98","author":[{"given":"Jonna B.","family":"Westover","sequence":"first","affiliation":[{"name":"Department of Animal, Dairy and Veterinary Sciences, Utah State University, Logan, Utah, USA"},{"name":"Institute for Antiviral Research, Utah State University, Logan, Utah, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kie Hoon","family":"Jung","sequence":"additional","affiliation":[{"name":"Department of Animal, Dairy and Veterinary Sciences, Utah State University, Logan, Utah, USA"},{"name":"Institute for Antiviral Research, Utah State University, Logan, Utah, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cigdem","family":"Alkan","sequence":"additional","affiliation":[{"name":"Department of Pathology, The University of Texas Medical Branch, Galveston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirsten M.","family":"Boardman","sequence":"additional","affiliation":[{"name":"Department of Animal, Dairy and Veterinary Sciences, Utah State University, Logan, Utah, USA"},{"name":"Institute for Antiviral Research, Utah State University, Logan, Utah, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnaud J.","family":"Van Wettere","sequence":"additional","affiliation":[{"name":"Department of Animal, Dairy and Veterinary Sciences, Utah State University, Logan, Utah, USA"},{"name":"Utah Veterinary Diagnostic Laboratory, Logan, Utah, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig","family":"Martens","sequence":"additional","affiliation":[{"name":"Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inioska","family":"Rojas","sequence":"additional","affiliation":[{"name":"Department of Animal, Dairy and Veterinary Sciences, Utah State University, Logan, Utah, USA"},{"name":"Institute for Antiviral Research, Utah State University, Logan, Utah, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip","family":"Hicks","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron J.","family":"Thomas","sequence":"additional","affiliation":[{"name":"Department of Animal, Dairy and Veterinary Sciences, Utah State University, Logan, Utah, USA"},{"name":"Center for Integrated BioSystems, Utah State University, Logan, Utah, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manohar T.","family":"Saindane","sequence":"additional","affiliation":[{"name":"Emory Institute for Drug Development, Emory University, Atlanta, Georgia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory R.","family":"Bluemling","sequence":"additional","affiliation":[{"name":"Emory Institute for Drug Development, Emory University, Atlanta, Georgia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuli","family":"Mao","sequence":"additional","affiliation":[{"name":"Emory Institute for Drug Development, Emory University, Atlanta, Georgia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander A.","family":"Kolykhalov","sequence":"additional","affiliation":[{"name":"Emory Institute for Drug Development, Emory University, Atlanta, Georgia, USA"},{"name":"Drug Innovation Ventures at Emory (DRIVE), Atlanta, Georgia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael G.","family":"Natchus","sequence":"additional","affiliation":[{"name":"Emory Institute for Drug Development, Emory University, Atlanta, Georgia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Bates","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George R.","family":"Painter","sequence":"additional","affiliation":[{"name":"Emory Institute for Drug Development, Emory University, Atlanta, Georgia, USA"},{"name":"Drug Innovation Ventures at Emory (DRIVE), Atlanta, Georgia, USA"},{"name":"Department of Pharmacology, Emory University School of Medicine, Atlanta, Georgia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8318-2783","authenticated-orcid":true,"given":"Tetsuro","family":"Ikegami","sequence":"additional","affiliation":[{"name":"Department of Pathology, The University of Texas Medical Branch, Galveston, Texas, USA"},{"name":"The Sealy Institute for Vaccine Sciences, The University of Texas Medical Branch, Galveston, Texas, USA"},{"name":"The Center for Biodefense and Emerging Infectious Diseases, The University of Texas Medical Branch, Galveston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9113-2575","authenticated-orcid":true,"given":"Brian B.","family":"Gowen","sequence":"additional","affiliation":[{"name":"Department of Animal, Dairy and Veterinary 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