{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T18:55:18Z","timestamp":1773082518180,"version":"3.50.1"},"reference-count":36,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T00:00:00Z","timestamp":1772928000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Health","award":["#2023-NI-016-02"],"award-info":[{"award-number":["#2023-NI-016-02"]}]},{"name":"National Institute of Health","award":["6634-319-210-11"],"award-info":[{"award-number":["6634-319-210-11"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne viral disease with high case\u2013fatality rates in East Asia, yet no licensed vaccines are currently available. Here, we generated attenuated severe fever with thrombocytopenia syndrome virus (SFTSV) strains through serial passage in Huh-7 cells and evaluated their pathogenicity, immunogenicity, and protective efficacy. Attenuation candidates were selected based on reduced pathogenicity, estimated based on the median lethal dose (LD50), and genetic sequencing was performed to identify mutations associated with attenuation. In C57BL\/6 IFNAR\u2212\/\u2212 mice, the attenuated strain exhibited markedly reduced virulence and viral loads while inducing robust virus-specific IgG, neutralizing antibody, and cellular immune responses. Notably, immunization with the attenuated strain conferred complete protection against lethal challenge with heterologous SFTSV genotypes. Genomic analysis revealed nonsynonymous mutations in the RNA-dependent RNA polymerase (RdRp), glycoprotein, and NSs genes, implicating alterations in viral replication, entry, and immune evasion. Collectively, these findings demonstrate that serial cell-culture passage can generate attenuated SFTSV strains that retain strong immunogenicity and cross-protective efficacy, supporting their potential as live-attenuated vaccine candidates for SFTS.<\/jats:p>","DOI":"10.3390\/v18030333","type":"journal-article","created":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T11:06:52Z","timestamp":1773054412000},"page":"333","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Serial Cell-Culture Passage of Severe Fever with Thrombocytopenia Syndrome Virus Attenuates Virulence and Confers Protective Immunity in Mice"],"prefix":"10.3390","volume":"18","author":[{"given":"Jihee","family":"Kim","sequence":"first","affiliation":[{"name":"Division of Acute Viral Diseases, Center for Emerging Virus Research, National Institute of Infectious Diseases, National Institute of Health, Korea Disease Control and Prevention Agency, Cheongju-si 28159, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Young-Eui","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Acute Viral Diseases, Center for Emerging Virus Research, National Institute of Infectious Diseases, National Institute of Health, Korea Disease Control and Prevention Agency, Cheongju-si 28159, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hae Ji","family":"Kang","sequence":"additional","affiliation":[{"name":"Division of Acute Viral Diseases, Center for Emerging Virus Research, National Institute of Infectious Diseases, National Institute of Health, Korea Disease Control and Prevention Agency, Cheongju-si 28159, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jungsang","family":"Ryou","sequence":"additional","affiliation":[{"name":"Division of Acute Viral Diseases, Center for Emerging Virus Research, National Institute of Infectious Diseases, National Institute of Health, Korea Disease Control and Prevention Agency, Cheongju-si 28159, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hyuk","family":"Chu","sequence":"additional","affiliation":[{"name":"Division of Acute Viral Diseases, Center for Emerging Virus Research, National Institute of Infectious Diseases, National Institute of Health, Korea Disease Control and Prevention Agency, Cheongju-si 28159, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2087-3661","authenticated-orcid":false,"given":"Seok-Min","family":"Yun","sequence":"additional","affiliation":[{"name":"Division of Acute Viral Diseases, Center for Emerging Virus Research, National Institute of Infectious Diseases, National Institute of Health, Korea Disease Control and Prevention Agency, Cheongju-si 28159, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2520343","DOI":"10.1080\/21505594.2025.2520343","article-title":"Bandavirus dabieense: A review of epidemiology, clinical characteristics, pathophysiology, treatment and prevention","volume":"16","author":"Peng","year":"2025","journal-title":"Virulence"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1523","DOI":"10.1056\/NEJMoa1010095","article-title":"Fever with thrombocytopenia associated with a novel bunyavirus in China","volume":"364","author":"Yu","year":"2011","journal-title":"N. 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