{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T06:13:09Z","timestamp":1765260789958,"version":"3.46.0"},"reference-count":61,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,12,7]],"date-time":"2025-12-07T00:00:00Z","timestamp":1765065600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32170203"],"award-info":[{"award-number":["32170203"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Natural Science Foundation of Chongqing, China","award":["CSTB2022NSCQ-MSX0573"],"award-info":[{"award-number":["CSTB2022NSCQ-MSX0573"]}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"crossref","award":["SWU-XDJH202323"],"award-info":[{"award-number":["SWU-XDJH202323"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JoF"],"abstract":"<jats:p>Cryptococcus neoformans is a fungal pathogen commonly found in the environment. It mainly infects immunocompromised individuals, causing cryptococcal pneumonia and meningitis, which result in hundreds of thousands of deaths each year. Zinc finger proteins, with zinc finger domains, are common across organisms and serve many biological functions. In this study, we identified and characterized Zfp2, a C3HC4-type zinc finger protein, which regulates cell fusion and virulence in C. neoformans. Stress tests showed that the zfp2\u0394 mutant is hypersensitive to SDS, Congo red, NaCl, KCl, caspofungin, and fluconazole, suggesting that Zfp2 helps maintain cell membrane or wall integrity in C. neoformans. Notably, deleting ZFP2 reduced capsule size, while its overexpression led to capsule enlargement. The zfp2\u0394 mutants also demonstrated a growth defect at 37 \u00b0C. Cell fusion assay showed that Zfp2 is essential for cell fusion during sexual reproduction, as zfp2\u0394 mutants could not fuse during bilateral mating. To understand why the zfp2\u0394 mutants failed to fuse, we examined key genes in the pheromone response pathway and found that Zfp2 may affect cell fusion by regulating this pathway. Finally, a virulence test in mice showed that both ZFP2 deletion and overexpression significantly reduced C. neoformans\u2019 virulence. Overall, our research suggests that the zinc finger protein Zfp2 is vital for cell fusion and virulence in C. neoformans.<\/jats:p>","DOI":"10.3390\/jof11120868","type":"journal-article","created":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T16:20:29Z","timestamp":1765210829000},"page":"868","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Zinc Finger Protein Zfp2 Regulates Cell\u2013Cell Fusion and Virulence in Cryptococcus neoformans"],"prefix":"10.3390","volume":"11","author":[{"given":"Cheng-Li","family":"Fan","sequence":"first","affiliation":[{"name":"College of Animal Science and Technology, Southwest University, Chongqing 400715, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lin","family":"Li","sequence":"additional","affiliation":[{"name":"Wanzhou District Center for Disease Control and Prevention, Chongqing 404199, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ji-Chong","family":"Shi","sequence":"additional","affiliation":[{"name":"Medical Research Institute, Southwest University, Chongqing 400715, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9111-8826","authenticated-orcid":false,"given":"Tong-Bao","family":"Liu","sequence":"additional","affiliation":[{"name":"Medical Research Institute, Southwest University, Chongqing 400715, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Casadevall, A., and Perfect, J.R. 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