{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T02:02:32Z","timestamp":1768528952311,"version":"3.49.0"},"reference-count":56,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2022,7,29]],"date-time":"2022-07-29T00:00:00Z","timestamp":1659052800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Key-Area Research and Development Program of Guangdong Province","award":["2021B0202040002"],"award-info":[{"award-number":["2021B0202040002"]}]},{"name":"Key-Area Research and Development Program of Guangdong Province","award":["FREU2022-04"],"award-info":[{"award-number":["FREU2022-04"]}]},{"name":"Key-Area Research and Development Program of Guangdong Province","award":["31930115"],"award-info":[{"award-number":["31930115"]}]},{"name":"Key-Area Research and Development Program of Guangdong Province","award":["U20A20102"],"award-info":[{"award-number":["U20A20102"]}]},{"name":"Key-Area Research and Development Program of Guangdong Province","award":["311021006"],"award-info":[{"award-number":["311021006"]}]},{"name":"Key Laboratory of South China Sea Fishery Resources Exploitation and Utilization, Ministry of Agriculture and Rural Affairs","award":["2021B0202040002"],"award-info":[{"award-number":["2021B0202040002"]}]},{"name":"Key Laboratory of South China Sea Fishery Resources Exploitation and Utilization, Ministry of Agriculture and Rural Affairs","award":["FREU2022-04"],"award-info":[{"award-number":["FREU2022-04"]}]},{"name":"Key Laboratory of South China Sea Fishery Resources Exploitation and Utilization, Ministry of Agriculture and Rural Affairs","award":["31930115"],"award-info":[{"award-number":["31930115"]}]},{"name":"Key Laboratory of South China Sea Fishery Resources Exploitation and Utilization, Ministry of Agriculture and Rural Affairs","award":["U20A20102"],"award-info":[{"award-number":["U20A20102"]}]},{"name":"Key Laboratory of South China Sea Fishery Resources Exploitation and Utilization, Ministry of Agriculture and Rural Affairs","award":["311021006"],"award-info":[{"award-number":["311021006"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["2021B0202040002"],"award-info":[{"award-number":["2021B0202040002"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["FREU2022-04"],"award-info":[{"award-number":["FREU2022-04"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31930115"],"award-info":[{"award-number":["31930115"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["U20A20102"],"award-info":[{"award-number":["U20A20102"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["311021006"],"award-info":[{"award-number":["311021006"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Innovation Group Project of Southern Marine Science and Engineering Guangdong Laboratory (Zhuhai)","award":["2021B0202040002"],"award-info":[{"award-number":["2021B0202040002"]}]},{"name":"Innovation Group Project of Southern Marine Science and Engineering Guangdong Laboratory (Zhuhai)","award":["FREU2022-04"],"award-info":[{"award-number":["FREU2022-04"]}]},{"name":"Innovation Group Project of Southern Marine Science and Engineering Guangdong Laboratory (Zhuhai)","award":["31930115"],"award-info":[{"award-number":["31930115"]}]},{"name":"Innovation Group Project of Southern Marine Science and Engineering Guangdong Laboratory (Zhuhai)","award":["U20A20102"],"award-info":[{"award-number":["U20A20102"]}]},{"name":"Innovation Group Project of Southern Marine Science and Engineering Guangdong Laboratory (Zhuhai)","award":["311021006"],"award-info":[{"award-number":["311021006"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>(1) Background: Lysosomal aspartic protease Cathepsin D (CD) is a key regulator and signaling molecule in various biological processes including activation and degradation of intracellular proteins, the antigen process and programmed cell death. However, the function of fish CD in virus infection remains largely unknown. (2) Methods: The functions of the CD gene response to SGIV infection was determined with light microscopy, reverse transcription quantitative PCR, Western blot and flow cytometry. (3) Results: In this study, Ec-Cathepsin D (Ec-CD) was cloned and identified from the orange-spotted grouper, Epinephelus coioides. The open reading frame (ORF) of Ec-CD consisted of 1191 nucleotides encoding a 396 amino acid protein with a predicted molecular mass of 43.17 kDa. Ec-CD possessed typical CD structural features including an N-terminal signal peptide, a propeptide region and a mature domain including two glycosylation sites and two active sites, which were conserved in other CD sequences. Ec-CD was predominantly expressed in the spleen and kidneys of healthy groupers. A subcellular localization assay indicated that Ec-CD was mainly distributed in the cytoplasm. Ec-CD expression was suppressed by SGIV stimulation and Ec-CD-overexpressing inhibited SGIV replication, SGIV-induced apoptosis, caspase 3\/8\/9 activity and the activation of reporter gene p53 and activating protein-1 (AP-1) in vitro. Simultaneously, Ec-CD overexpression obviously restrained the activated mitogen-activated protein kinase (MAPK) pathways, including extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK). In addition, Ec-CD overexpression negatively regulated the transcription level of pro-inflammatory cytokines and activation of the NF-\u03baB promotor. (4) Conclusions: Our findings revealed that the Ec-CD possibly served a function during SGIV infection.<\/jats:p>","DOI":"10.3390\/v14081680","type":"journal-article","created":{"date-parts":[[2022,8,1]],"date-time":"2022-08-01T23:49:27Z","timestamp":1659397767000},"page":"1680","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Functional Analysis of the Cathepsin D Gene Response to SGIV Infection in the Orange-Spotted Grouper, Epinephelus coioides"],"prefix":"10.3390","volume":"14","author":[{"given":"Yuexuan","family":"Wang","sequence":"first","affiliation":[{"name":"Laboratory for Lingnan Modern Agriculture, College of Marine Sciences, South China Agricultural University, Guangzhou 510642, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Honglin","family":"Han","sequence":"additional","affiliation":[{"name":"Laboratory for Lingnan Modern Agriculture, College of Marine Sciences, South China Agricultural University, Guangzhou 510642, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0712-5514","authenticated-orcid":false,"given":"Kecheng","family":"Zhu","sequence":"additional","affiliation":[{"name":"Key Laboratory of South China Sea Fishery Resources Exploitation and Utilization, Ministry of Agriculture and Rural Affairs, South China Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Guangzhou 510300, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suifeng","family":"Xu","sequence":"additional","affiliation":[{"name":"Laboratory for Lingnan Modern Agriculture, College of Marine Sciences, South China Agricultural University, Guangzhou 510642, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chengzong","family":"Han","sequence":"additional","affiliation":[{"name":"Laboratory for Lingnan Modern Agriculture, College of Marine Sciences, South China Agricultural University, Guangzhou 510642, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yunxiang","family":"Jiang","sequence":"additional","affiliation":[{"name":"Laboratory for Lingnan Modern Agriculture, College of Marine Sciences, South China Agricultural University, Guangzhou 510642, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shina","family":"Wei","sequence":"additional","affiliation":[{"name":"Laboratory for Lingnan Modern Agriculture, College of Marine Sciences, South China Agricultural University, Guangzhou 510642, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1188-9023","authenticated-orcid":false,"given":"Qiwei","family":"Qin","sequence":"additional","affiliation":[{"name":"Laboratory for Lingnan Modern Agriculture, College of Marine Sciences, South China Agricultural University, Guangzhou 510642, China"},{"name":"Southern Marine Science and Engineering Guangdong Laboratory (Zhuhai), Zhuhai 528478, China"},{"name":"Laboratory for Marine Biology and Biotechnology, Qingdao National Laboratory for Marine Science and Technology, Qingdao 266000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1270","DOI":"10.1016\/j.fsi.2011.09.012","article-title":"Identification and expressional analysis of two cathepsins from half-smooth tongue sole (Cynoglossus semilaevis)","volume":"31","author":"Chen","year":"2011","journal-title":"Fish Shellfish Immunol."},{"key":"ref_2","first-page":"163","article-title":"The function of cathepsins B, D, and X in atherosclerosis","volume":"6","author":"Zhao","year":"2016","journal-title":"Am. J. Cardiovasc. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.critrevonc.2008.02.008","article-title":"Cathepsin D--many functions of one aspartic protease","volume":"68","author":"Benes","year":"2008","journal-title":"Crit. Rev. Oncol. Hematol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"5406","DOI":"10.1074\/jbc.M504670200","article-title":"Cathepsin D is present in human eccrine sweat and involved in the postsecretory processing of the antimicrobial peptide DCD-1L","volume":"281","author":"Baechle","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1248\/bpb.33.22","article-title":"Translocation of lysosomal cathepsin D caused by oxidative stress or proteasome inhibition in primary cultured neurons and astrocytes","volume":"33","author":"Miura","year":"2010","journal-title":"Biol. Pharm. Bull."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1967","DOI":"10.1038\/sj.onc.1209221","article-title":"Overexpression of both catalytically active and -inactive cathepsin D by cancer cells enhances apoptosis-dependent chemo-sensitivity","volume":"25","author":"Beaujouin","year":"2006","journal-title":"Oncogene"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/0165-2478(93)90018-W","article-title":"Role of cathepsin D in the degradation of human serum albumin by peritoneal macrophages and veiled cells in antigen presentation","volume":"37","author":"Rhodes","year":"1993","journal-title":"Immunol. Lett."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1002\/med.21394","article-title":"The Role of Cathepsin D in the Pathogenesis of Human Neurodegenerative Disorders","volume":"36","author":"Vidoni","year":"2016","journal-title":"Med. Res. Rev."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1186\/s40425-019-0498-z","article-title":"Immunotherapy of triple-negative breast cancer with cathepsin D-targeting antibodies","volume":"7","author":"Ashraf","year":"2019","journal-title":"J. Immunother. Cancer"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1393","DOI":"10.1080\/14728222.2016.1252334","article-title":"Cathepsin D as a therapeutic target in Alzheimer\u2019s disease","volume":"20","author":"Tramutola","year":"2016","journal-title":"Expert Opin. Ther. Targets"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"7088","DOI":"10.1016\/S0021-9258(17)32945-9","article-title":"Mode of inhibition of acid proteases by pepstatin","volume":"251","author":"Marciniszyn","year":"1976","journal-title":"J. Biol. Chem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"10749","DOI":"10.1021\/jm301630s","article-title":"Cyanobacterial peptides as a prototype for the design of potent beta-secretase inhibitors and the development of selective chemical probes for other aspartic proteases","volume":"55","author":"Liu","year":"2012","journal-title":"J. Med. Chem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1002\/psc.1254","article-title":"Total synthesis and stereochemical reassignment of tasiamide B","volume":"16","author":"Sun","year":"2010","journal-title":"J. Pept. Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e3154","DOI":"10.1002\/psc.3154","article-title":"Design, synthesis, and bioactivities of tasiamide B derivatives as cathepsin D inhibitors","volume":"25","author":"Li","year":"2019","journal-title":"J. Pept. Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1002\/psc.3014","article-title":"Cyanobacterial peptides as a prototype for the design of cathepsin D inhibitors","volume":"23","author":"Xu","year":"2017","journal-title":"J. Pept. Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1963","DOI":"10.1016\/j.bmc.2015.03.034","article-title":"Design, synthesis and biological evaluation of tasiamide B derivatives as BACE1 inhibitors","volume":"23","author":"Liu","year":"2015","journal-title":"Bioorg. Med. Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.dci.2014.10.014","article-title":"Identification and characterization of a cathepsin D homologue from lampreys (Lampetra japonica)","volume":"49","author":"Xiao","year":"2015","journal-title":"Dev. Comp. Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/j.fsi.2014.07.013","article-title":"Cloning, characterisation, and expression analysis of the cathepsin D gene from rock bream (Oplegnathus fasciatus)","volume":"40","author":"Choi","year":"2014","journal-title":"Fish Shellfish Immunol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1207","DOI":"10.1016\/j.fsi.2012.09.012","article-title":"Molecular cloning, characterization and expression of cathepsin D from grass carp (Ctenopharyngodon idella)","volume":"33","author":"Dong","year":"2012","journal-title":"Fish Shellfish Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1136\/vr.150.1.15","article-title":"Initial investigations into two viruses isolated from marine food fish in Singapore","volume":"150","author":"Chang","year":"2002","journal-title":"Vet. Rec."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/S0166-0934(01)00350-0","article-title":"Electron microscopic observations of a marine fish iridovirus isolated from brown-spotted grouper, Epinephelus tauvina","volume":"98","author":"Qin","year":"2001","journal-title":"J. Virol. Methods"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1016\/j.fsi.2018.10.027","article-title":"Characterization of cathepsin C from orange-spotted grouper, Epinephelus coioides involved in SGIV infection","volume":"84","author":"Wei","year":"2019","journal-title":"Fish Shellfish Immunol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1016\/j.fsi.2013.11.006","article-title":"Characterization of cathepsin B gene from orange-spotted grouper, Epinephelus coioides involved in SGIV infection","volume":"36","author":"Wei","year":"2014","journal-title":"Fish Shellfish Immunol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1489","DOI":"10.1099\/jgv.0.000811","article-title":"Fish miR-146a promotes Singapore grouper iridovirus infection by regulating cell apoptosis and NF-kappaB activation","volume":"98","author":"Ni","year":"2017","journal-title":"J. Gen. Virol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1111\/j.1749-6632.1965.tb14302.x","article-title":"A permanent cell line from the fathead minnow (Pimephales promelas)","volume":"126","author":"Gravell","year":"1965","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1094","DOI":"10.1016\/j.fsi.2013.01.010","article-title":"Molecular cloning, expression and functional analysis of ISG15 in orange-spotted grouper, Epinephelus coioides","volume":"34","author":"Huang","year":"2013","journal-title":"Fish Shellfish Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1569","DOI":"10.1007\/s10495-007-0089-1","article-title":"Mitochondrion-mediated apoptosis induced by Rana grylio virus infection in fish cells","volume":"12","author":"Huang","year":"2007","journal-title":"Apoptosis"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1007\/s10495-011-0616-y","article-title":"Singapore grouper iridovirus, a large DNA virus, induces nonapoptotic cell death by a cell type dependent fashion and evokes ERK signaling","volume":"16","author":"Huang","year":"2011","journal-title":"Apoptosis"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2184","DOI":"10.1007\/s11064-020-03080-5","article-title":"Impaired Autophagy Flux is Associated with Proinflammatory Microglia Activation Following Japanese Encephalitis Virus Infection","volume":"45","author":"Kumar","year":"2020","journal-title":"Neurochem. Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1016\/j.fsi.2008.09.011","article-title":"Molecular cloning, characterization and expression analysis of cathepsin D gene from turbot Scophthalmus maximus","volume":"26","author":"Jia","year":"2009","journal-title":"Fish Shellfish Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/j.cbpc.2004.01.006","article-title":"Todarepsin, a new cathepsin D from hepatopancreas of Japanese common squid (Todarodes pacificus)","volume":"137","author":"Komai","year":"2004","journal-title":"Comp. Biochem. Physiol. B Biochem. Mol. Biol."},{"key":"ref_32","first-page":"w13042","article-title":"Cathepsins and their involvement in immune responses","volume":"140","author":"Conus","year":"2010","journal-title":"Swiss Med. Wkly."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"5745","DOI":"10.1007\/s11033-021-06565-w","article-title":"Pathogenesis of the inflammatory bowel disease in context of SARS-COV-2 infection","volume":"48","author":"Dvornikova","year":"2021","journal-title":"Mol. Biol. Rep."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"200160","DOI":"10.1098\/rsob.200160","article-title":"Cytokine storm and COVID-19: A chronicle of pro-inflammatory cytokines","volume":"10","author":"Fara","year":"2020","journal-title":"Open Biol."},{"key":"ref_35","first-page":"327","article-title":"Induction of pro-inflammatory cytokines (IL-1 and IL-6) and lung inflammation by Coronavirus-19 (COVI-19 or SARS-CoV-2): Anti-inflammatory strategies","volume":"34","author":"Conti","year":"2020","journal-title":"J. Biol. Regul. Homeost Agents"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"104761","DOI":"10.1016\/j.phrs.2020.104761","article-title":"Lianhuaqingwen exerts anti-viral and anti-inflammatory activity against novel coronavirus (SARS-CoV-2)","volume":"156","author":"Runfeng","year":"2020","journal-title":"Pharmacol. Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.chom.2016.01.010","article-title":"The cGAS-STING Defense Pathway and Its Counteraction by Viruses","volume":"19","author":"Ma","year":"2016","journal-title":"Cell Host Microbe"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1080\/14728222.2020.1746765","article-title":"Cysteine cathepsins as therapeutic targets in inflammatory diseases","volume":"24","author":"Vizovisek","year":"2020","journal-title":"Expert Opin. Ther. Targets"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s10753-016-0447-7","article-title":"Indirubin Inhibits LPS-Induced Inflammation via TLR4 Abrogation Mediated by the NF-kB and MAPK Signaling Pathways","volume":"40","author":"Lai","year":"2017","journal-title":"Inflammation"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.cmet.2010.12.008","article-title":"NF-kappaB, inflammation, and metabolic disease","volume":"13","author":"Baker","year":"2011","journal-title":"Cell Metab."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"a001651","DOI":"10.1101\/cshperspect.a001651","article-title":"The nuclear factor NF-kappaB pathway in inflammation","volume":"1","author":"Lawrence","year":"2009","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"e9183","DOI":"10.1590\/1414-431x20209183","article-title":"Lapiferin protects against H1N1 virus-induced pulmonary inflammation by negatively regulating NF-kB signaling","volume":"53","author":"Pei","year":"2020","journal-title":"Braz. J. Med. Biol. Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"930","DOI":"10.1016\/j.micinf.2012.03.007","article-title":"Japanese encephalitis virus NS1\u2019 protein depends on pseudoknot secondary structure and is cleaved by caspase during virus infection and cell apoptosis","volume":"14","author":"Sun","year":"2012","journal-title":"Microbes Infect."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1038\/nrmicro2071","article-title":"Apoptosis in animal models of virus-induced disease","volume":"7","author":"Clarke","year":"2009","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2614","DOI":"10.1128\/JVI.02311-06","article-title":"Caspase 3-dependent cell death of neurons contributes to the pathogenesis of West Nile virus encephalitis","volume":"81","author":"Samuel","year":"2007","journal-title":"J. Virol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"e99","DOI":"10.1038\/cddis.2010.77","article-title":"Mechanisms of HIV-associated lymphocyte apoptosis: 2010","volume":"1","author":"Cummins","year":"2010","journal-title":"Cell Death Dis."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2951","DOI":"10.1182\/blood.V96.9.2951","article-title":"Mechanisms of HIV-associated lymphocyte apoptosis","volume":"96","author":"Badley","year":"2000","journal-title":"Blood"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1016\/j.fsi.2019.06.043","article-title":"A novel MKK gene (EcMKK6) in Epinephelus coioides: Identification, characterization and its response to Vibrio alginolyticus and SGIV infection","volume":"92","author":"Su","year":"2019","journal-title":"Fish Shellfish Immunol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"329","DOI":"10.3389\/fcimb.2019.00329","article-title":"Grouper TRADD Mediates Innate Antiviral Immune Responses and Apoptosis Induced by Singapore Grouper Iridovirus (SGIV) Infection","volume":"9","author":"Zhang","year":"2019","journal-title":"Front. Cell Infect. Microbiol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"121","DOI":"10.3389\/fmicb.2016.00121","article-title":"JNK1 Derived from Orange-Spotted Grouper, Epinephelus coioides, Involving in the Evasion and Infection of Singapore Grouper Iridovirus (SGIV)","volume":"7","author":"Guo","year":"2016","journal-title":"Front. Microbiol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"21142","DOI":"10.1074\/jbc.M111.306399","article-title":"Cathepsin D primes caspase-8 activation by multiple intra-chain proteolysis","volume":"287","author":"Conus","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/S1044-7431(03)00035-6","article-title":"Involvement of two different cell death pathways in retinal atrophy of cathepsin D-deficient mice","volume":"22","author":"Koike","year":"2003","journal-title":"Mol. Cell Neurosci."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1869","DOI":"10.1093\/carcin\/bgn147","article-title":"Cathepsin D protects human neuroblastoma cells from doxorubicin-induced cell death","volume":"29","author":"Sagulenko","year":"2008","journal-title":"Carcinogenesis"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2838","DOI":"10.1038\/sj.onc.1207556","article-title":"Mitogen-activated protein kinases in apoptosis regulation","volume":"23","author":"Wada","year":"2004","journal-title":"Oncogene"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1007\/s10495-011-0595-z","article-title":"Involvement of the mitogen-activated protein kinase pathway in soft-shelled turtle iridovirus-induced apoptosis","volume":"16","author":"Huang","year":"2011","journal-title":"Apoptosis"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/j.virol.2007.09.010","article-title":"Modulation of iridovirus-induced apoptosis by endocytosis, early expression, JNK, and apical caspase","volume":"370","author":"Chitnis","year":"2008","journal-title":"Virology"}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/14\/8\/1680\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:59:37Z","timestamp":1760140777000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/14\/8\/1680"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,29]]},"references-count":56,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2022,8]]}},"alternative-id":["v14081680"],"URL":"https:\/\/doi.org\/10.3390\/v14081680","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,29]]}}}