{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T20:39:05Z","timestamp":1790282345492,"version":"4.1.0"},"reference-count":27,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2021,3,29]],"date-time":"2021-03-29T00:00:00Z","timestamp":1616976000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AI153433"],"award-info":[{"award-number":["R01AI153433"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["K22AI125474"],"award-info":[{"award-number":["K22AI125474"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>La Crosse virus (LACV) is the leading cause of pediatric viral encephalitis in North America, and is an important public health pathogen. Historically, studies involving LACV pathogenesis have focused on lineage I strains, but no former work has explored the pathogenesis between or within lineages. Given the absence of LACV disease in endemic regions where a robust entomological risk exists, we hypothesize that some LACV strains are attenuated and demonstrate reduced neuroinvasiveness. Herein, we compared four viral strains representing all three lineages to determine differences in neurovirulence or neuroinvasiveness using three murine models. A representative strain from lineage I was shown to be the most lethal, causing &gt;50% mortality in each of the three mouse studies. However, other strains only presented excessive mortality (&gt;50%) within the suckling mouse neurovirulence model. Neurovirulence was comparable among strains, but viruses differed in their neuroinvasive capacities. Our studies also showed that viruses within lineage III vary in pathogenesis with contemporaneous strains, showing reduced neuroinvasiveness compared to an ancestral strain from the same U.S. state (i.e., Connecticut). These findings demonstrate that LACV strains differ markedly in pathogenesis, and that strain selection is important for assessing vaccine and therapeutic efficacies.<\/jats:p>","DOI":"10.3390\/pathogens10040400","type":"journal-article","created":{"date-parts":[[2021,3,29]],"date-time":"2021-03-29T16:01:57Z","timestamp":1617033717000},"page":"400","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["La Crosse Virus Shows Strain-Specific Differences in Pathogenesis"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1293-6255","authenticated-orcid":false,"given":"Sarah N.","family":"Wilson","sequence":"first","affiliation":[{"name":"Department of Entomology, College of Agriculture and Life Sciences, Fralin Life Science Institute, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krisangel","family":"L\u00f3pez","sequence":"additional","affiliation":[{"name":"Department of Entomology, College of Agriculture and Life Sciences, Fralin Life Science Institute, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheryl","family":"Coutermash-Ott","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences and Pathobiology, Virginia Tech, VA-MD College of Veterinary Medicine, Blacksburg, VA 24061, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dawn I.","family":"Auguste","sequence":"additional","affiliation":[{"name":"Department of Entomology, College of Agriculture and Life Sciences, Fralin Life Science Institute, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8837-9673","authenticated-orcid":false,"given":"Danielle L.","family":"Porier","sequence":"additional","affiliation":[{"name":"Department of Entomology, College of Agriculture and Life Sciences, Fralin Life Science Institute, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip M.","family":"Armstrong","sequence":"additional","affiliation":[{"name":"Environmental Sciences, Center for Vector Biology and Zoonotic Diseases, The Connecticut Agricultural Experiment Station, New Haven, CT 06504, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theodore G.","family":"Andreadis","sequence":"additional","affiliation":[{"name":"Environmental Sciences, Center for Vector Biology and Zoonotic Diseases, The Connecticut Agricultural Experiment Station, New Haven, CT 06504, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9683-0353","authenticated-orcid":false,"given":"Gillian","family":"Eastwood","sequence":"additional","affiliation":[{"name":"Department of Entomology, College of Agriculture and Life Sciences, Fralin Life Science Institute, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA"},{"name":"Center for Emerging, Zoonotic, and Arthropod-Borne Pathogens, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9048-0041","authenticated-orcid":false,"given":"Albert J.","family":"Auguste","sequence":"additional","affiliation":[{"name":"Department of Entomology, College of Agriculture and Life Sciences, Fralin Life Science Institute, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA"},{"name":"Center for Emerging, Zoonotic, and Arthropod-Borne Pathogens, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,29]]},"reference":[{"key":"ref_1","unstructured":"Howley, P.M., Knipe, D.M., and Whelan, S. 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