{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T05:01:33Z","timestamp":1784091693492,"version":"3.55.0"},"reference-count":56,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2022,4,28]],"date-time":"2022-04-28T00:00:00Z","timestamp":1651104000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Science Council, Taiwan, Republic of China","award":["NSC 101-3011-P-006-006"],"award-info":[{"award-number":["NSC 101-3011-P-006-006"]}]},{"name":"National Science Council, Taiwan, Republic of China","award":["MOST 104-2313-B-006-003"],"award-info":[{"award-number":["MOST 104-2313-B-006-003"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>The molecular pathogenesis of infectious spleen and kidney necrosis virus (ISKNV) infections is important but has rarely been studied in connection to host organelle behavior. In the present study, we demonstrated that ISKNV can induce host cell death via a pro-apoptotic Bcl-2 and anti-apoptotic Bcl-2 family member imbalance in mitochondrial membrane potential (MMP or \u0394\u03a8m) regulation in GF-1 cells. The results of our study on ISKNV infection showed that it can induce host cell death by up to 80% at day 5 post-infection. Subsequently, in an apoptotic assay, ISKNV infection was seen to induce an increase in Annexin-V-positive signals by 20% and in propidium iodide (PI) staining-positive signals by up to 30% at day 5 (D5) in GF-1 cells. Then, through our studies on the mechanism of cell death in mitochondria function, we found that ISKNV can induce MMP loss by up to 58% and 78% at days 4 and 5 with a JC1 dye staining assay. Furthermore, we found that pro-apoptotic members Bax and Bak were upregulated from the early replication stage (day one) to the late stage (day 5), but the expression profiles were very dynamically different. On the other hand, by Western blotted analysis, the anti-apoptotic members Bcl-2 and Bcl-xL were upregulated very quickly at the same time from day one (two-fold) and continued to maintain this level at day five. Finally, we found that pro-apoptotic death signals strongly activated the downstream signals of caspase-9 and -3. Taken together, these results suggest that ISKNV infection can induce Bax\/Bak-mediated cell death signaling downstream of caspase-9 and -3 activation. During the viral replication cycle with the cell death induction process, the anti-apoptotic members Bcl-2\/Bcl-xL interacted with the pro-apoptotic members Bax\/Bak to maintain the mitochondrial function in the dynamic interaction so as to maintain the MMP in GF-1 cells. These findings may provide insights into DNA-virus control and treatment.<\/jats:p>","DOI":"10.3390\/v14050922","type":"journal-article","created":{"date-parts":[[2022,4,28]],"date-time":"2022-04-28T23:52:30Z","timestamp":1651189950000},"page":"922","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Infectious Spleen and Kidney Necrosis Virus (ISKNV) Triggers Mitochondria-Mediated Dynamic Interaction Signals via an Imbalance of Bax\/Bak over Bcl-2\/Bcl-xL in Fish Cells"],"prefix":"10.3390","volume":"14","author":[{"given":"Pin-Han","family":"Chen","sequence":"first","affiliation":[{"name":"Lab of Molecular Virology and Biotechnology, Department of Biotechnology and Bioindustry Sciences, Institute of Biotechnology, National Cheng Kung University, No. 1. University Road, Tainan City 701, Taiwan"},{"name":"Institute of Biotechnology, National Cheng Kung University, No. 1. University Road, Tainan City 701, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsai-Ching","family":"Hsueh","sequence":"additional","affiliation":[{"name":"Lab of Molecular Virology and Biotechnology, Department of Biotechnology and Bioindustry Sciences, Institute of Biotechnology, National Cheng Kung University, No. 1. University Road, Tainan City 701, Taiwan"},{"name":"Institute of Biotechnology, National Cheng Kung University, No. 1. University Road, Tainan City 701, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jen-Leih","family":"Wu","sequence":"additional","affiliation":[{"name":"Laboratory of Marine Molecular Biology and Biotechnology, Institute of Cellular and Organismic Biology, Academia Sinica, Nankang, Taipei 115, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3886-5192","authenticated-orcid":false,"given":"Jiann-Ruey","family":"Hong","sequence":"additional","affiliation":[{"name":"Lab of Molecular Virology and Biotechnology, Department of Biotechnology and Bioindustry Sciences, Institute of Biotechnology, National Cheng Kung University, No. 1. University Road, Tainan City 701, Taiwan"},{"name":"Institute of Biotechnology, National Cheng Kung University, No. 1. University Road, Tainan City 701, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"521","DOI":"10.3390\/v4040521","article-title":"Review: Megalocytivirus","volume":"4","author":"Kurita","year":"2012","journal-title":"Viruses"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1111\/j.1753-5131.2012.01075.x","article-title":"Megalocytivirus infection in fish","volume":"4","author":"Subramaniam","year":"2012","journal-title":"Rev. Aquac."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/S0065-3527(05)65006-3","article-title":"A decade of advances in iridovirus research","volume":"65","author":"Williams","year":"2005","journal-title":"Adv. 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