{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T23:56:05Z","timestamp":1781567765819,"version":"3.54.5"},"reference-count":58,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2020,2,25]],"date-time":"2020-02-25T00:00:00Z","timestamp":1582588800000},"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>Resident cells in the skin serve as the first innate line of defense against insect-borne pathogens, but the role of these cell types in promoting or limiting arbovirus replication is not completely understood. Here, we have examined the outcome of infection of cultured human keratinocyte cells with La Crosse virus (LACV), using a spontaneously transformed cell line, HaCaT. In single cycle infections, keratinocyte HaCaT cells supported rapid and high level LACV replication, resulting in high virus yields and extensive caspase-dependent cell death. By contrast, multi-cycle LACV replication in HaCaT cells was restricted by an antiviral response elicited by the production of both IFN-\u03b2 and IFN-\u03bb. During low multiplicity LACV infections, HaCaT cell death was seen in non-infected bystander cells. Media from LACV-infected cells induced caspase-dependent killing of na\u00efve non-infected HaCaT cells, and this bystander cell death was relieved by IFN-\u03b2 neutralizing antibodies or by an inhibitor of JAK-STAT signaling. Na\u00efve HaCaT cells showed dose-dependent killing by treatment with exogenous IFN-\u03b2 but not IFN-\u03bb. Our data suggest a model whereby keratinocytes produce IFNs which limit virus spread through both antiviral signaling and by induction of bystander cell death of potential new target cells for infection.<\/jats:p>","DOI":"10.3390\/v12030253","type":"journal-article","created":{"date-parts":[[2020,2,26]],"date-time":"2020-02-26T04:18:29Z","timestamp":1582690709000},"page":"253","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["La Crosse Virus Infection of Human Keratinocytes Leads to Interferon-Dependent Apoptosis of Bystander Non-Infected Cells In Vitro"],"prefix":"10.3390","volume":"12","author":[{"given":"Maria","family":"Cruz","sequence":"first","affiliation":[{"name":"Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL 32827, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Griffith","family":"Parks","sequence":"additional","affiliation":[{"name":"Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL 32827, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,2,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1630","DOI":"10.1111\/j.1462-5822.2007.00955.x","article-title":"The skin as interface in the transmission of arthropod-borne pathogens","volume":"9","author":"Frischknecht","year":"2007","journal-title":"Cell. 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