{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,30]],"date-time":"2026-08-30T15:37:48Z","timestamp":1788104268181,"version":"build-2803163510"},"reference-count":61,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2022YFF1000302"],"award-info":[{"award-number":["2022YFF1000302"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32273171"],"award-info":[{"award-number":["32273171"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Strategic Priority Research Program of the Chinese Academy of Sciences","award":["XDB0730300"],"award-info":[{"award-number":["XDB0730300"]}]},{"name":"Strategic Priority Research Program of the Chinese Academy of Sciences","award":["XDA24010308"],"award-info":[{"award-number":["XDA24010308"]}]},{"name":"Natural Science Foundation of Hubei Province of China","award":["2022CFA110"],"award-info":[{"award-number":["2022CFA110"]}]},{"name":"Agricultural Biological Breeding-2030","award":["2023ZD04065"],"award-info":[{"award-number":["2023ZD04065"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The von Hippel-Lindau (VHL) tumor suppressor gene VHL is a classic tumor suppressor that has been identified in family members with clear cell renal cell carcinomas, central nervous system and retinal hemangioblastomas, phaeochromocytomas, and pancreatic neuroendocrine tumors. The well-defined function of VHL is to mediate proteasomal degradation of hydroxylated hypoxia-inducible factor \u03b1 proteins, resulting in the downregulation of hypoxia-responsive gene expression. Previously, we reported that VHL inhibits antiviral signaling by targeting mitochondrial antiviral signaling protein (MAVS) for proteasomal degradation. However, due to the lack of a viable animal model, the physiological role and underlying mechanism of VHL in antiviral immunity remains to be elucidated. In this study, we found that heterozygous vhl-deficient zebrafish have normal neutrophils and no gross phenotypic alterations. However, upon spring viremia of carp virus or grass carp reovirus infection, antiviral gene expression is induced in vhl+\/\u2212 zebrafish compared with wild-type zebrafish. In addition, spring viremia of carp virus replication is suppressed in vhl+\/\u2212 zebrafish, owing to the enhancement of antiviral ability. Furthermore, by crossing with mavs\u2212\/\u2212 zebrafish line, we observed that disruption of mavs in vhl+\/\u2212 zebrafish abrogates the viral resistance exhibited in vhl+\/\u2212 zebrafish. Thus, we reveal that heterozygous vhl deficiency enhances the antiviral ability of zebrafish against RNA virus infection, and we provide genetic evidence to support that zebrafish mavs serves as a mediator for the suppressive role of vhl in antiviral innate immunity.<\/jats:p>","DOI":"10.1093\/jimmun\/vkae017","type":"journal-article","created":{"date-parts":[[2025,1,23]],"date-time":"2025-01-23T14:58:28Z","timestamp":1737644308000},"page":"167-179","source":"Crossref","is-referenced-by-count":2,"title":["Genetic evidence for the suppressive role of zebrafish vhl targeting mavs in antiviral innate immunity during RNA virus infection"],"prefix":"10.1093","volume":"214","author":[{"given":"Xueyi","family":"Sun","sequence":"first","affiliation":[{"name":"Key Laboratory of Breeding Biotechnology and Sustainable Aquaculture, Institute of Hydrobiology, Chinese Academy of Sciences , Wuhan, P. R.","place":["China"]},{"name":"University of Chinese Academy of Sciences , Beijing, P. R.","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9400-2992","authenticated-orcid":false,"given":"Wen","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Breeding Biotechnology and Sustainable Aquaculture, Institute of Hydrobiology, Chinese Academy of Sciences , Wuhan, P. R.","place":["China"]},{"name":"University of Chinese Academy of Sciences , Beijing, P. R.","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunchun","family":"Zhu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Breeding Biotechnology and Sustainable Aquaculture, Institute of Hydrobiology, Chinese Academy of Sciences , Wuhan, P. R.","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-8289-1538","authenticated-orcid":false,"given":"Zixuan","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Breeding Biotechnology and Sustainable Aquaculture, Institute of Hydrobiology, Chinese Academy of Sciences , Wuhan, P. R.","place":["China"]},{"name":"University of Chinese Academy of Sciences , Beijing, P. R.","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyan","family":"Deng","sequence":"additional","affiliation":[{"name":"Key Laboratory of Breeding Biotechnology and Sustainable Aquaculture, Institute of Hydrobiology, Chinese Academy of Sciences , Wuhan, P. R.","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Liao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Breeding Biotechnology and Sustainable Aquaculture, Institute of Hydrobiology, Chinese Academy of Sciences , Wuhan, P. R.","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2978-0616","authenticated-orcid":false,"given":"Wuhan","family":"Xiao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Breeding Biotechnology and Sustainable Aquaculture, Institute of Hydrobiology, Chinese Academy of Sciences , Wuhan, P. R.","place":["China"]},{"name":"University of Chinese Academy of Sciences , Beijing, P. R.","place":["China"]},{"name":"Hubei Hongshan Laboratory , Wuhan, P. R.","place":["China"]},{"name":"The Innovation of Seed Design, Chinese Academy of Sciences , Wuhan, P. R.","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9338-7440","authenticated-orcid":false,"given":"Xing","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Breeding Biotechnology and Sustainable Aquaculture, Institute of Hydrobiology, Chinese Academy of Sciences , Wuhan, P. R.","place":["China"]},{"name":"Hubei Hongshan Laboratory , Wuhan, P. R.","place":["China"]},{"name":"The Innovation of Seed Design, Chinese Academy of Sciences , Wuhan, P. 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