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系統識別號 U0026-2108201810284100
論文名稱(中文) 探討神經壞死病毒感染石斑魚細胞株所誘導ROS介導引起AMPK/mTOR/ ULK1的自噬作用路徑
論文名稱(英文) Studies on betanodavirus-induced ROS-mediated autophagy via AMPK/mTOR/ULK1 signaling pathway in grouper fish cells
校院名稱 成功大學
系所名稱(中) 生物科技與產業科學系
系所名稱(英) Department of Biotechnology and Bioindustry Sciences
學年度 106
學期 2
出版年 107
研究生(中文) 林幸霓
研究生(英文) Hsing-Ni Lin
學號 L66054059
學位類別 碩士
語文別 中文
論文頁數 115頁
口試委員 指導教授-洪健睿
口試委員-吳金洌
口試委員-蔣輯武
口試委員-劉校生
口試委員-邱品文
中文關鍵字 神經壞死病毒  活性氧分子 (ROS)  自噬作用  AMPK  mTOR  ULK1 
英文關鍵字 Betanodavirus  autophagy  antioxidants  AMPK/mTOR/ULK1 
學科別分類
中文摘要 神經壞死病毒 (RGNNV)為重創石斑魚經濟重要病毒之一,先前研究發現RGNNV利用細胞自噬作用進行病毒複製。自噬作用為細胞代謝機制,功能為維持細胞恆定,分解回收老舊及受損胞器,提供能量或原料經合成代謝產生新的胞器,細胞面臨壓力誘導發生。本實驗室研究證實RGNNV感染石斑魚鰭細胞株 (GF-1)產生經活性氧分子 (H2O2, O2-)誘導的自噬作用,且病毒感染使自噬作用上游分子mTOR活性增加。然而RGNNV誘導之自噬訊號經由什麼路徑尚不知曉。本研究欲探討RGNNV感染GF-1下誘導AMPK/mTOR/ULK1的自噬路徑的調節關係。Western分析發現病毒感染mTOR活化與ULKSer757的磷酸化程度隨時間具有相關性。本研究利用不同類型的抗氧化劑處理抑制不同的ROS探討GF-1受病毒感染下自噬路徑,發現ROS產生與AMPK/mTOR/ULK1的自噬路徑的調節關係有關。若利用抗氧化劑減少ROS產生,會降低mTOR活化的程度及控制ULKSer757的磷酸化程度。同時讓病毒複製下降,降低感染力。ROS訊號為自噬作用的上游,當控制ROS同時也控制了病毒複製。另外利用UV光使病毒不活化,能降低細胞自噬的啟動,發現其可有效抑制病毒基因表現及蛋白合成,也因此減弱對細胞的傷害。依上述幾點推斷病毒誘導細胞自噬作用系統,來進行調控病毒複製。
英文摘要 Nervous necrosis virus is one of the most important economic viruses in grouper group. In previous studies, it was found that nerve necrosis virus uses the original autophagy of cells to carry out virus replication. Autophagy is the metabolic mechanism of cells. Its function is to maintain constant intracellular cells, to decompose and recover old and damaged organelles, to provide energy for anabolic production of new organelles, or as a raw material for cell production and assembly. When cells are under stress, they will be induced to occur. Our laboratory studies have confirmed that nerve necrosis virus (RGNNV)-infected grouper fin cell line (GF-1) produces autophagy induced by reactive oxygen species (H2O2, O2-), and viral infection causes autophagy upstream. Molecular mTOR activity is increased. However, it is not known whether the autophagy signal induced by necrosis virus is via the AMPK/mTOR or AMPK/ULK1 pathway. Therefore, this study was to investigate the regulatory relationship between the autophagy pathways of AMPK/mTOR or AMPK/ULK1 induced by necrosis virus infection. From protein expression analysis, it was found that the degree of phosphorylation of viral infection with mTOR was correlated with the degree of phosphorylation of ULKSer757 over time. In this study, different types of antioxidants were used to inhibit different types of ROS. To investigate the resistance of grouper fin cell lines to virus infection, it was found that ROS production is related to the regulatory relationship between mTOR/ULK1 autophagy pathway. It has been found that the use of antioxidants to reduce ROS production reduces the extent of mTOR activation and controls the degree of phosphorylation of ULKSer757. At the same time, it also allows the virus to copy and reduce the infection. Therefore, it was confirmed that the ROS signal was upstream of autophagy, and when ROS was controlled, virus replication was also controlled. On the other hand, the use of UV light to disable the virus can reduce the initiation of autophagy, and it is found to be effective in inhibiting viral gene expression and protein synthesis, thereby reducing damage to cells. Based on the above points, the virus-induced autophagy system was inferred to regulate viral replication.
論文目次 中文摘要 I
英文摘要 II
誌謝 V
目錄 VI
表目錄 VIII
圖目錄 IX
附錄目錄 XI
縮寫表 XII
一、研究背景 1
1-1台灣石斑魚養殖概況 1
1-2神經壞死病毒背景說明 4
1-3活性氧分子 (ROS) 10
1-4自噬作用 15
1-5自噬作用與病毒感染的互動 19
1-6蛋白Beclin-1與Bcl-2之間的互動 22
1-7紫外光處理使病毒失去活性 24
1-8研究目的 24
二、材料與方法 26
2-1實驗材料 26
2-2實驗儀器 35
2-3實驗方法及步驟 37
三、結果 43
3-1 RGNNV誘發GF-1細胞產生ROS引起自噬作用 43
3-2 RGNNV感染誘導氧化壓力對mTOR/ULKSer757的影響 45
3-3 UV光處理病毒感染誘導氧化壓力對mTOR/ULKSer757的影響 46
3-4 RGNNV感染誘導氧化壓力對於細胞死亡的影響 47
四、討論 51
4-1神經壞死病毒誘發細胞內氧化壓力失衡 51
4-2活性氧分子對於自噬作用機制的影響 52
4-3神經壞死病毒操作自噬作用機制 53
4-4結論 54
參考文獻 55
圖表 74
附錄 108
參考文獻 呂明偉、韓宛娟,石斑魚的病毒性疾病,科學發展 472,66-71,2012。
李昂融,抗凋亡家族蛋白Bcl-2與Bcl-xL對野田病毒所誘導魚類宿主細胞死亡與自噬作用之研究,國立成功大學生物科技研究所碩士論文,2014。
李威漢,探討神經壞死病毒複製與啟動細胞自噬之相關性,國立成功大學生物科技研究所碩士論文,2016。
沈士新、鄭安倉、劉秉忠、林正輝、冉繁華,台灣石斑魚產業現況與趨勢,水產養殖生技38,1-7,2014。
張芝瑋,神經壞死病毒誘發石斑魚細胞氧化壓力與病毒蛋白B1影響氧化壓力之探討,國立成功大學生物科技研究所碩士論文,2009。
張峻齊,中國大陸石斑魚發展趨勢與我國因應對策,財團法人農業科技研究院,1-8,2016。
梁友,石斑魚集約化健康養殖技術,中國水產科學研究院黃海水產研究所,水產前沿2,83-85,2016。
陳宗嶽、王廷瑜、徐浩軒,石斑魚的恐怖病毒殺手,科學發展 482,44-48,2013。
陳俐伽,神經壞死病毒非結構蛋白B1基因選殖及其功能之探討,國立成功大學生物科技研究所碩士論文,2007。
陳博榕,神經壞死病毒所誘導之活性氧化分子對於自噬作用的調節,國立成功大學生物科技研究所碩士論文,2014。
黃淑敏,石斑魚虹彩病毒疫苗研發,獸醫專訊3,31-34,2011。
楊玉婷、陳葦芋、陳政忻,石斑魚產業概況及趨勢,農業生技產業19,24-29,2009。
葉信利,變性的奧祕,科學發展473,6-13,2012。
詹滿色,臺灣石斑魚產銷及價格分析,海大漁業推廣 46,33-46,2016。
廖浤鈞,神經壞死病毒所誘導細胞內氧化壓力能影響細胞自噬體吞噬作用及病毒複製之研究,國立成功大學生物科技研究所碩士論文,2012。
蔡佳錚,魚類神經壞死病毒症研究近狀,獸醫專訓4,18-26,2011。
鄭金華,安全繁養殖技術,科學發展473,20-25,2012。
蘇偉成,石斑魚產業發展,科學發展473,4-5,2012。
Alers, S., Loffler, A. S., Wesselborg, S. and Stork, B. Role of AMPK-mTOR-Ulk1/2 in the regulation of autophagy: cross talk, shortcuts, and feedbacks. Molecular and Cellular Biology 32, 2-11, 2012.
Aquilano, K., Baldelli, S. and Ciriolo, M.R. Glutathione: New roles in redox signaling for an old antioxidant. Frontiers in Pharmacology 5, 196, 2014.
Astrid, R. B. and John, C. Reed. Therapeutics targeting Bcl-2 in hematological Malignancies. Biochemical Journal 474, 3643-3657, 2017.
Azad, M.B., Chen,Y. and Gibson, S.B. Regulation of Autophagy by Reactive Oxygen Species (ROS): Implications for Cancer Progression and Treatment. Antioxidants and Redox Signaling 11, 777-790, 2009.
Balaban, R. S., Nemoto, S. and Finkel, T. Mitochondria, oxidants, and aging. Cell 120, 483-495, 2005.
Berryman, S.Foot-and-mouth disease virus induces autophagosomes during cell entry via a class III phosphatidylinositol 3-kinase-independent pathway. Journal of Virology 86, 12940-12953, 2012.
Biering, S. B., Choi, J., Halstrom, R. A., Brown, H. M., Beatty, W. L., Lee, S., McCune, B. T., Dominici, E., Williams, L. E., Orchard, R. C., Wilen, C. B., Yamamoto, M., Coers, J., Taylor, G.A. and Hwang, S. Viral replication complexes are targeted by LC3-guided interferon-inducible GTPases. Cell Host and Microbe 22, 74-85, 2017.
Bigarre, L., Cabon, J., Baud, M., Heimann, M., Body, A., Lieffrig, F. and Castric, J. Outbreak of betanodavirus infection in Tilapia, Oreochromis niloticus (L.), in fresh water. Journal of Fish Disease 32, 667-673, 2009.
Birben, E., Sahiner, U. M., Sackesen, C., Erzurum, S. and Kalayci, O. Oxidative Stress and Antioxidant Defense. World Allergy Organization Journal 5, 9-19, 2012.
Blancquaert, S., Wang, L., Paternot, S., Coulonval, K., Dumont, J.E., Harris, T.E. and Roger, P.P. cAMP-dependent activation of mammalian target of rapamycin (mTOR) in thyroid cells. Implication in mitogenesis and activation of CDK4. Molecular Endocrinology 24, 1453-1468, 2010.
Boonyaratpalin, S., Supamattaya, K., Kasornchanda, J. and Hoffmann, R.W. Picona-like virus associated with mortality and spongious encephalopathy in grouper, Epinephelus malabaricus. Disease of Aquatic Organisms 26, 75-80, 1996.
Brown, D. G., Sun, X. M. and Cohen, G. M. Dexamethasone-induced apoptosis involves cleavage of DNA to large fragments prior to internucleosomal fragmentation. The Journal of Biological Chemistry 268, 3037-3039, 1993.
Bryan, H.K., Olayanju, A., Goldring, C.E. and Park, B.K. The Nrf2 cell defence pathway: Keap1-dependent and -independent mechanisms of regulation. Biochemical Pharmacology 85, 705-717, 2013.
Cadenas E. Biochemistry of oxygen toxicity. Annual Review of Biochemistry 58, 79-110, 1989.
Chang, C. W., Su, Y. C., Her, G. M., Ken, C. F. and Hong, J. R. Betanodavirus Induces Oxidative Stress-Mediated Cell Death That Prevented by Anti-Oxidants and Zfcatalase in Fish Cells. Plos One 6, 25853, 2011.
Chen, L. J., Su, Y. C. and Hong, J. R. Betanodavirus non-structural protein B1: A novel anti-necrotic death factor that modulates cell death in early replication cycle in fish cells. Virology 385, 444-454, 2009.
Chen, P., Cescon, M. and Bonaldo, P.Autophagy-mediated regulation ofmacrophages and its applications for cancer. Autophagy 10, 192-200, 2014.
Chen, S. P., Yang, H. L., Lin, H.Y., Chen, M.C., Wu, J.L. and Hong, J.R. Betanodavirus induces phosphatidylserine exposure and loss of mitochondrial membrane potential in secondary necrotic cells, both of which are blocked by bongkrekic acid. Virology 347, 379-391, 2006.
Chen, Y. and Klionsky, D.J. The regulation of autophagy-unanswered questions. Journal of Cell Science 124, 161-170, 2011.
Chen, Y. Q. and Gibson, S. B. Is mitochondrial generation of reactive oxygen speciesa trigger for autophagy? Autophagy 4, 246-248, 2008.
Chen, Y. Q., McMillan-Ward, E., Kong, J. M., Israels, S. J. and Gibson, S. B. Mitochondrial electron-transport-chain inhibitors of complexes I and II induce autophagic cell death mediated by reactive oxygen species. Journal of Cell Science 120, 4155-4166, 2007.
Chen, Y., Azad, M.B. and Gibson, S.B. Superoxide is the major reactive oxygen species regulating autophagy. Cell Death and Differentiation 16, 1040-1052, 2009.
Cheong, H., Lindsten, T., Wu, J., Lu, C. and Thompson, C. B. Ammonia-induced autophagy is independent of ULK1/ULK2 kinases. Proceedings of the National Academy of Sciences 27, 11121-11126, 2011.
Chiramel, A. I., Brady, N. R. and Bartenschlager, R. Divergent roles of autophagy in virus infection. Cells 2, 83-104, 2013.
Choi, Y., Bowman, J. W. and Jung, J. U. Autophagy during viral infection - a double-edged sword. Nature Review Microbiology 16, 341-354, 2018.
Cicchini, M., Karantza,V. and Xia, B. Molecular Pathways: Autophagy in Cancer- A Matter of Timing and Context. Clinical Cancer Research 21,498-504, 2015.
Criollo, A., Maiuri, M. C., Tasdemir, E., Vitale, I., Fiebig, A. A., Andrews, D., Molgó, J., Díaz, J., Lavandero, S., Harper, F., Pierron, G., di Stefano, D., Rizzuto, R., Szabadkai, G. and Kroemer, G. Regulation of autophagy by the inositol trisphosphate receptor. Cell Death and Differentiation 14, 1029-1039, 2007.
Cuconati, A. and White, E. Viral homologs of BCL-2: role of apoptosis in the regulation of virus infection. Genes and Development 16, 2465-2478, 2002.
Dales, S., Eggers, H. J., Tamm, I. and Palade, G. E. Electron microscopic study of the formation of poliovirus. Virology 26, 379-389, 1965.
Deramaudt, T.B., Dill, C. and Bonay, M. Regulation of oxidative stress by Nrf2 in the pathophysiology of infectious diseases. Médecine et Maladies Infectieuses 43, 100-107, 2013.
Deretic, V., Saitoh, T. and Akira, S. Autophagy in infection, inflammation and immunity. Nature Reviews Immunology 13, 722-737, 2013.
Djouder, N., Tuerk, R. D., Suter, M., Salvioni, P., Thali, R. F., Scholz, R., Vaahtomeri, K., Auchli, Y., Rechsteiner, H., Brunisholz, R. A., Viollet, B,, Ma kela, T. P., Wallimann, T., Neumann, D. and Krek, W. PKA phosphorylates and inactivates AMPKa to promote efficient lipolysis. European Molecular Biology Organization Journal 29, 469-48, 2010.
Edinger, A.L. and Thompson, C.B. Death by design: apoptosis, necrosis and autophagy. Current Opinion in Cell Biology 16, 663-669. 2004.
Emerling,B.M., Weinberg, F., Snyder, C., Burgess, Z., Mutlu, G.M., Viollet, B., Budinger, G.R. and Chandel, N.S. Hypoxic activation of AMPK is dependent on mitochondrial ROS but independent of an increase in AMP/ATP ratio. Free Radical Biology and Medicine 46, 1386-1391, 2009.
Escaffre, O., Halliday, H., Borisevich, V., Casola, A. and Rockx, B. Oxidative stress in NIPAH virus-infected human small airway epithelial cells. Journal of General Virology 96, 2961-2970, 2015.
Finkel, T. Signal transduction by reactive oxygen species. The Journal of Cell Biology 194, 7-15, 2011.
Fuchs, Y. and Steller, H. Live to die another way: modes of programmed cell death and the signals emanating from dying cells. Nature Reviews Molecular Cell Biology 16, 329-344, 2015.
Funderburk, S. F., Wang, Q. J. and Yue, Z. The Beclin 1-VPS34 complex–at the crossroads of autophagy and beyond. Trends in Cell Biology 20, 355-362, 2010.
Galluzzi, L., Vitale, I., Abrams, J. M., Alnemri, E. S., Baehrecke, E. H., Blagosklonny, M. V., Dawson, T. M., Dawson, V. L., ElDeiry, W. S. and Fulda, S. Molecular definitions of cell death subroutines: Recommendations of the Nomenclature Committee on Cell Death. Cell Death and Differentiation 19, 107-120, 2012.
Gloire, G., LegrandPoels, S. and Piette, J. NF-κB activation by reactive oxygen species: Fifteen years later. Biochemical Pharmacology 72, 1493-1505, 2006.
GonzalezDosal, R., Horan, K. A., Rahbek, S. H., Ichijo, H. and Chen, Z. J. HSV infection induces production of ROS, which potentiate signaling from pattern recognition receptors: role for S-glutathionylation of TRAF3 and 6. Public Library of Science Pathogens 7, e1002250, 2011.
Green, D. R. and Llambi, F. Cell Death Signaling. Cold Spring Harbor Perspectives in Biology 7, a006080, 2015.
Grotmol, S., Totland, G. K. and Kryvi, H. Detection of a nodavirus-like agent in heart tissue from reared Atlantic salmon Salmo salar suffering from cardiac myopathy syndrome (CMS). Diseases of Aquatic Organisms 29, 79-84, 1997.
Grotmol, S., Totland, G.K., Torud, K. and Hjeltnes, B.K. Vacuolating encephalopathy and retinopathy associated with a nodavirus-like agent: a probable cause of mass mortality of cultured larval and juvenile Atlantic halibut hippoglossus. Diseases of Aquatic Organisms 29, 85-97, 1997.
Gullberg, R.C., Jordan, Steel. J. and Moon, S.L. Oxidative stress influences positive strand RNA virus genome synthesis and capping. Virology 475, 219-229, 2015.
Gwinn, D.M., Shackelford, D.B., Egan, D.F., Mihaylova, M.M., Mery, A., Vasquez, D.S., Turk, B.E. and Shaw, R.J. AMPK phosphorylation of raptor mediates a metabolic checkpoint. Molecular Cell 30, 214-226, 2008.
Hardie, D.G. AMP-activated/SNF1 protein kinases: conserved guardians of cellular energy. Nature Reviews Molecular Cell Biology 8, 774-785, 2007.
Harman, D. The aging process. Proceedings of the National Academy of Sciences 78, 7124-7128, 1981.
Hockenbery, D. M., Oltvai, Z. N., Yin, X. M., Milliman, C. L.and Korsmeyer, S.J. Bcl-2 functions in an antioxidant pathway to prevent apoptosis. Cell 75, 241-251, 1993.
Honda, O., Kuroda, M., Joja, I., Asaumi, J., Takeda, Y., Akaki, S., Togami, I., Kanazawa, S., Kawasaki, S. and Hiraki, Y. Assessment of secondary necrosis of Jurkat cells using a new microscopic system and double staining method with annexin V and propidium iodide. International Journal of Oncology 16, 283-291, 2000.
Hong, Liu., Yong, Teng., Xiaocong, Zheng., Yurong, Wu., Xiayang, Xie., Junqiang, He., Yiyou, Ye. and Zhixin, Wu. Complete sequence of a viral nervous necrosis virus (NNV) isolated from red-spotted grouper (Epinephelus akaara) in China. Archives of Virology 157, 777-782, 2012.
Hosakote, Y. M., Brasier, A. R., Casola, A., Garofalo, R. P., Kurosky, A. and Lyles, D. S. Respiratory syncytial virus infection triggers epithelial HMGB1 release as a damage-associated molecular pattern promoting a monocytic inflammatory response. Journal of Virology 90, 9618-9631, 2016.
Huimin, B., Yun, W., Xiang, L., Haitao, M., Yan, L., Shili, H., Zhengli, S. and Xinwen, C. Isolation and characterization of a novel alphanodavirus. Virology Journal 8, 311, 2011.
Itakura, E., Kishi, C., Inoue, K. and Mizushima, N. Beclin-1 forms two distinct phosphatidylinositol 3-kinase complexes with mammalian Atg14 and UVRAG. Molecular Biology of the Cell 19, 5360-5372, 2008.
Iwamoto, T., Nakai, T., Mori, K., Arimoto, M. and Furusawa, I. Cloning of the fish cell line SSN-1 for piscine nodaviruses. Diseases of Aquatic Organisms 43, 81-89, 2000.
Jackson, W. T. Subversion of cellular autophagosomal machinery by RNA viruses. Public Library of Science Biology 3, e156, 2005.
Jørgensen, C., Enberg, K., Dunlop, E. S., Arlinghaus, R., Boukal, D. S., Brander, K., Ernande, B., Gårdmark, A. G., Johnston, F., Matsumura, S., Pardoe, H., Raab, K., Silva, A., Vainikka, A., Dieckmann, U., Heino, M. and Rijnsdorp, A. D. Ecology: Managing Evolving Fish Stocks. Science 318, 1247-1248, 2007.
Jose M. B. P., Yongjie, W., Valentina, S., Maria, C. M., Zhongju, Z., Guido, K. and Beth, Levine. BAX and BAK1 are dispensable for ABT-737-induced dissociation of the BCL2-BECN1 complex and autophagy, Autophagy 11, 452-459, 2015.
Kametaka, S., Okano, T., Ohsumi, M. and Ohsumi, Y. Apg14p and Apg6/Vps30p form a protein complex essential for autophagy in the yeast, Saccharomyces cerevisiae. Journal of Biological Chemistry 273, 22284-22291, 1998.
Kane, D. J., Sarafian, T. A., Anton, R., Hahn, H., Gralla, E. B., Valentine, J. S., Ord, T. and Bredesen, D. E. Bcl-2 inhibition of neural death: decreased generation of reactive oxygen species. Science 262, 1274-1277, 1993.
Kang, R., Zeh, H. J., Lotze, M. T. and Tang, D. The Beclin 1 network regulates autophagy and apoptosis. Cell Death and Differentiation 18, 571-580, 2011.
Kara, H. M., Chaoui, L., Derbal1, F., Zaidi, R., Boisse´son, C. de., Baud, M., and Bigarre´, L. Betanodavirus-associated mortalities of adult wild groupers Epinephelus marginatus (Lowe) and Epinephelus costae (Steindachner) in Algeria. Journal of Fish Disease 37, 273-278, 2014.
Katherine Bergmann., UV-C Irradiation: A New Viral Inactivation Method for Biopharmaceuticals. American Pharmaceutical Review, 2014.
Katherine, R., Parzych and Daniel, J. K. An Overview of Autophagy: Morphology, Mechanism, and Regulation. Antioxidants and Redox Signaling 20, 460-473, 2014.
Keawcharoen, J., Techangamsuwa, S., Ponpornpisit, A., Lombardini, E. D., Patchimasiri, T., and Pirarat, N. Genetic characterization of a betanodavirus isolated from a clinical disease outbreak in farm-raised tilapia Oreochromis niloticus (L). in Thailand. Journal of Fish Diseases 38, 49-54, 2015.
Kerr, J.F., Wyllie, A.H. and Currie, A.R. Apoptosis: A basic biological phe-nomenon with wide-ranging implications in tissue kinetics. British Journal of Cancer 26, 239-257, 1972.
Kim, H. J., Kwag, H. L., Kim, D. G., Kang, B. K., Han, S. Y., Moon, H. and Kim, H.J. Assembly of the capsid protein of red-spotted grouper nervous necrosis virus during purification, and role of calcium ions in chromatography. Biotechnology and Bioprocess Engineering 21, 373-380, 2016.
Kim, H.J., Kim, C.H., Ryu, J.H., Kim. M.J. and Park, C.Y. Reactive oxygen species induce antiviral innate immune response through IFN-lambda regulation in human nasal epithelial cells. American Journal of Respiratory Cell and Molecular Biology 49, 855-865, 2013.
Kim, J. O., Kim, W. S., Cho, J. K., Kim, K. M., Son, M. H. and Oh, M. J. Complete Genome Sequence of Nervous Necrosis Virus Isolated from Sevenband Grouper (Epinephelus septemfasciatus) in South Korea. Genome Announcements 2, 1264-1314, 2014.
Kim, J., Kundu, M., Viollet, B. and Guan, K. L. AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1. Nature Cell Biology 13, 132-141, 2011.
Kim, S.H., Park, S., Yu, H.S., Ko, K.H., Park, H.G. and Kim, Y.S. The antipsychotic agent clozapine induces autophagy via the AMPK-ULK1-Beclin1 signaling pathway in the rat frontal cortex. Progress in Neuro-Psychopharmacology and Biological Psychiatry 81, 96-104, 2018.
Klionsky, D. J. The autophagy connection. Developmental Cell 19, 11-12, 2010.
Kobashigawa, S., Kashino, G., Suzuki, K., Yamashita, S. and Mori, H. Ionizingradiation-induced cell death is partly caused by increase of mitochondrialreactive oxygen species in normal human fibroblast cells. Radiation Research 183, 455-464, 2015.
Krapfenbauer, K., Engidawork, E., Cairns, N., Fountoulakis, M. and G. Lubec, Aberrant expression of peroxiredoxin subtypes in neurodegenerative disorders. Brain Research 967, 152-160, 2003.
Kroemer, G. and Levine, B. Autophagic cell death: the story of a misnomer. Nature Reviews Molecular Cell Biology 9, 1004-1010, 2008.
Kroemer, G., Dallaporta, B. and Resche-Rigon, M.The mitochondrial death/life regulator in apoptosis and necrosis. Annual Review of Physiology 60, 619-642, 1998.
Ku, B. Structural and biochemical bases for the inhibition of autophagy and apoptosis by viral BCL-2 of murine gamma-herpesvirus 68. Public Library of Science Pathogens 4, e25, 2008.
Kyei, G. B. Autophagy pathway intersects with HIV-1 biosynthesis and regulates viral yields in macrophages. The Journal of Cell Biology 186, 255-268, 2009.
Landry,W.D. and Cotter, T. G. ROS signalling, NADPH oxidases and cancer.Biochemical Society Transactions 42, 934-938, 2014.
Larvae and Juveniles of Japanese Parrotfish, Oplegnathus-Fasciatus (Temminck and Schlegel). Journal of Fish Diseases 13, 69-77, 1990.
Lee, J.W., Park, S., Takahashi,Y. and Wang, H.G. The association of AMPK with ULK1 regulates autophagy. Public Library of Science One 5, e15394, 2010.
Levine, B., Sinha, S. and Kroemer, G. Bcl-2 family members: dual regulators of apoptosis and autophagy. Autophagy 4, 600-606, 2008.
Li, L., Tan, J., Miao, Y., Lei, P. and Zhang, Q. ROS and autophagy: interactions andmolecular regulatory mechanisms. Cellular and Molecular Neurobiology 35, 615-621, 2015.
Liang, Q., Changa, B., Kevin, F. B., Castroa, K.,Mina, C. K., Rodgersa, M. A., Shia, M., Gea, J., Fenga, P., Ohb, B. H. and Junga, J. U. Kaposi’s sarcoma-associated herpesvirus K7 modulates Rubicon-mediated inhibition of autophagosome maturation. Journal of Virology 87, 12499-12503, 2013.
Lin, L., Chen, Y. and Gibson, S.B. Starvation-induced autophagy is regulated by mitochondrial reactive oxygen species leading to AMPK activation. Cellular Signalling 25, 50-65, 2013.
Liu, C., Mo, L., Niu, Y., Li, X., Zhou, X. and Xu, X. The Role of Reactive Oxygen Species and Autophagy in Periodontitis and Their Potential Linkage. Front Physiology 8, 439, 2017.
Liu, H., Teng, Y., Zheng, X., Wu, Y., Xie, X., He, J., Ye, Y. and Wu, Z. Complete sequence of a viral nervous necrosis virus (NNV) isolated from red-spotted grouper (Epinephelus akaara) in China. Archives of Virology 157, 777-782, 2012.
Loschen, G., Azzi, A., Richter, C. and Flohe, L. Superoxide radicals as precursors of mitochondrial hydrogen peroxide. Federation of European Biochemical Societies 42, 68-72, 1974.
Low, C. F., Syarul, N. B., Chee, H. Y., Rozaini, M. Z.H. and Najiah, M. Betanodavirus: dissection of the viral life cycle. Journal of Fish Diseases 11, 1489-1496, 2017
Lucas, J. Aquaculture. Current Biology 25, R1064-R1065, 2015.
Ma Q. Role of nrf2 in oxidative stress and toxicity. Annual Review of Pharmacology and Toxicology 53, 401-426, 2013.
Maiuri, M. C., Criollo, A. and Kroemer, G. Crosstalk between apoptosis and autophagy within the Beclin 1 interactome. European Molecular Biology Organization Journal 29, 515-516, 2010.
Malikm, S. A., Orhon, I., Morselli, E., Criollo, A., Shen, S., Marino, G., BenYounes, A., Benit, P., Rustin, P. and Maiuri, M. C. BH3 mimetics activate multiple proautophagic pathways. Oncogene 30, 3918-3929, 2011.
Marino, G. and Kroemer, G. Mechanisms of apoptotic phosphatidylserine exposure. Cell Research 23, 1247-1248, 2013.
Massey, A., Kiffin, R. and Cuervo, A. M. Pathophysiology of chaperone-mediated autophagy. The International Journal of Biochemistry and Cell Biology 36, 2420-2434, 2004.
Matthew, R., Sandbulte, Anna, R., Spickler, Pamela, K., Zaabel, James, A. and Roth. Optimal Use of Vaccines for Control of Influenza A Virus in Swine. Vaccines 1, 22-23, 2015.
Mattson, M. P. NF-κB in the survival and plasticity of neurons. Journal Neurochemical Research 30, 883-893, 2005.
Mijaljica, D., Prescott, M. and Devenish, R. J. Microautophagy in mammalian cells: revisiting a 40-year-old conundrum. Autophagy 7, 673-682, 2011.
Min, B. Y., Kim, N. Y., Jang, E. S., Shin, C. M., Lee, S. H., Park, Y. S. and Kim, J. W. Ethanol potentiates hepatitis B virus replication through oxidative stress-dependent and -independent transcriptional activation. Biochemical and Biophysical Research Communications 431, 92-97, 2013.
Mizushima, N. and Komatsu, M. Autophagy: renovation of cells and tissues. Cell 147, 728-741, 2011.
Mizushima, N. Methods for monitoring autophagy. The International Journal of Biochemistry and Cell Biology 36, 2491-2502, 2004.
Mizushima, N. The role of the Atg1/ULK1 complex in autophagy regulation. Current Opinion in Cell Biology 22, 132-139, 2010.
Mori, K., Nakai, T., Muroga, K., Arimoto, M., Mushiake, K. and Furusawa, I. Properties of a new virus belonging to Nadaviridae found in larval striped jack (Peudocaranx dentex) with nervous necrosis. Virology 187, 368-371, 1992.
Mulvey, M., Poppers, J., Sternberg, D.and& Mohr, I. Regulation of eIF2alpha phosphorylation by different functions that act during discrete phases in the herpes simplex virus type 1 life cycle. Journal of Virology 77, 10917-10928, 2003.
Munday, B.L., Kwang, J. and Moody, N. Betanodavirus infections of teleost fish: a review. Journal of Fish Disease 25, 127-142, 2002.
Murphy, M. P. How mitochondria produce reactive oxygen species. Biochemical Journal 417, 1-13, 2009.
Nagai, T. and Nishizawa, T. Sequence of the non-structural protein gene encodedby RNA1 of striped jack nervous necrosis virus. Journal of General Virology 80, 3019-3022, 1999.
Nishizawa, T., Furuhashi, M., Nagai, T., Nakai, T. and Muroga, K. Genomic classification of fish nodaviruses by molecular phylogenetic analysis of the coat protein gene. Applied and Environmental Microbiology 63, 1633-1636, 1997.
Nogueira, V. and Hay, N. Molecular pathways: reactive oxygen specieshomeostasis in cancer cells and implications for cancer therapy. Clinical Cancer Research 19, 4309-4314, 2013.
Novo, E. and Parola, M. Redox mechanisms in hepatic chronic wound healing and fibrogenesis. Fibrogenesis and Tissue Repair 1, 5, 2008.
O’Donnell, V. Foot-and-mouth disease virus utilizes an autophagic pathway during viral replication. Virology 410, 142-150, 2011.
Olagnier, D., Peri, S., Steel, C., van Montfoort, N., Chiang, C., Beljanski, V. and Hiscott, J.Cellular oxidative stress response controls the antiviral and apoptotic programs in dengue virus-infected dendritic cells. Public Library of Science Pathogens 10, 1004566, 2014.
Parekh, V.V., Pabbisetty, S. K., Wu, L., Sebzda, E., Martinez, J., Zhang, J. and Van, K. L. Autophagy-related protein Vps34 controls the homeostasis and function of antigen cross-presenting CD8α+ dendritic cells. Proceedings of the National Academy of Sciences 114, E6371-E6380, 2017.
Park, J. M., Seo, M., Jung, C. H., Grunwald, D., Stone, M., Otto, N. M., Toso, E., Ahn, Y., Kyba, M., Griffin, T. J., Higgins, L. and Kim, D. H. ULK1 phosphorylates Ser30 of BECN1 in association with ATG14 to stimulate autophagy induction. Autophagy 14, 584-597, 2018.
Park, J. Y., Cho, J. K., Son, M. H., Kim, K. M., Han, K. H. and Park, J. M. Artificial Spawning Behavior and Development of Eggs, Larvae and Juveniles of the Red Spotted Grouper, Epinephelus akaara in Korea. Development and Reproduction 20, 31-40, 2016.
Parzych, K. R. and Klionsky, D. J. An overview of autophagy: morphology, mechanism, and regulation. Antioxidants and Redox Signaling 20, 460-473, 2014.
Patricia, B., Fulvio, R. and Patrice, C., Emerging regulation and functions of autophagy. Nature Cell Biology 15, 713-720, 2013.
Pattingre, S. Bcl-2 antiapoptotic proteins inhibit Beclin 1-dependent autophagy. Cell 122, 927-939, 2005.
Pattingre, S., Bauvy, C., Carpentier, S., Levade, T., Levine, B. and Codogno, P. Role of JNK1-dependent Bcl-2 phosphorylation in ceramide-induced macroautophagy. The Journal of Biological Chemistry 284, 2719-2728, 2009.
Rada, B. and Leto, T.L. Oxidative innate immune defenses by Nox/Duox family NADPH oxidases. Contributions to Microbiology 15, 164-187, 2008.
Rehman, Z. U., Qiu, X., Sun, Y., Liao, Y., Tan, L., Song, C. and Ding, C. Vitamin E Supplementation Ameliorates Newcastle Disease Virus-Induced Oxidative Stress and Alleviates Tissue Damage in the Brains of Chickens. Viruses 10, 173, 2018.
Reshi, L., Wu, J. L., Wang, H. V. and Hong, J. R. Aquatic viruses induce host cell death pathways and its application. Virus Research 211, 133-144, 2016.
Robinson, S. M. Coxsackievirus B exits the host cell in shed microvesicles displaying autophagosomal markers. Public Library of Science Pathology 10, 1004045, 2014.
Romao, S., Gannage, M. and Munz, C. Checking the garbage bin for problems in the house, or how autophagy assists in antigen presentation to the immune system. Seminars in Cancer Biology 23, 391-396, 2013.
Rubinsztein, D. C., Codogno, P. and Levine, B. Autophagy modulation as a potential therapeutic target for diverse diseases. Nature Reviews Drug Discovery 11, 709-730, 2012.
Ryan, C. Russell, Y. T., Haixin, Y., Hyun, W. P., Chang, Y. Y., Kim, J., Kim, H., Thomas, P. N., Dillin, A. and Guan, K .L. ULK1 induces autophagy by phosphorylating Beclin-1 and activating VPS34 lipid kinase. Nature Cell Biology 15, 741-750, 2013.
Salehi, B., Motamedi-Sedeh, F., Madadgar, O., Khalili, I., Ghalyan, Chi, Langroudi, A., Unger, H. and Wijewardana, V. Analysis of antigen conservation and inactivation of gamma-irradiated avian influenza virus subtype H9N2. Acta Microbiologica et Immunologica Hungarica 24, 1-9, 2018.
Samali, A., Gorman, A.M. and Cotter, T.G. Apoptosis the story so far. Experientia 52, 933-941, 1996.
Sancak, Y., Peterson, T. R., Shaul, Y. D., Lindquist, R. A., Thoreen, C. C., Bar-Peled, L. and Sabatini, D. M. The Rag GTPases bind raptor and mediate amino acid signaling to mTORC1. Science 320, 1496-1501, 2008.
Scherz-Shouval, R. and Elazar, Z. Regulation of autophagy by ROS: physiology and pathology. Trends in Biochemical Sciences 36, 30-38, 2011.
Scherz-Shouval, R., Shvets, E., Fass, E., Shorer, H., Gil, L. and Elazar, Z. Reactive oxygen species are essential for autophagy and specifically regulate the activity of Atg4. European Molecular Biology Organization Journal 26, 1749-1760, 2007.
Schneemann, A., Reddy, V. and Johnson, J.E. The structure and function of nodavirus particles: a paradigm for understanding chemical biology. Advances in Virus Research 50, 381-446, 1998.
Senft, D. and Ronai, Z. A. UPR, autophagy, and mitochondria crosstalk underlies the ER stress response. Trends in Biochemical Sciences 40, 141-148, 2015.
Shang, L., Chen, S., Du, F., Li, S., Zhao, L. and Wang, X. Nutrient starvation elicits an acute autophagic response mediated by Ulk1 dephosphorylation and its subsequent dissociation from AMPK. Proceedings of the National Academy of Sciences of the United States of America 108, 4788-4793, 2011.
Sharma, M., Sharma, K. B., Chauhan, S., Bhattacharyya, S., Vrati, S. and Kalia, M. Diphenyleneiodonium enhances oxidative stress and inhibits Japanese encephalitis virus induced autophagy and ER stress pathways. Biochemical and Biophysical Research Communications 502, 232-237, 2018.
Shetty, M., Maiti, B., Shivakumar Santhosh, K., Venugopal, M. N. and Karunasagar, I. Betanodavirus of marine and freshwater fish: distribution, genomic organization, diagnosis and control measures. Indian Journal of Virology 23, 114-123, 2012.
Shi, C. S. and Kehrl, J. H. MyD88 and Trif target Beclin 1 to trigger autophagy in macrophages. The Journal of Biological Chemistry 283, 33175-33182, 2008.
Sinha, S. and Levine, B. The autophagy effector Beclin 1: a novel BH3-only protein. Oncogene 27, 137-148, 2008.
Skliris, G.P., Krondiris, J.V., Sieris, D.C., Shinn, A.P., Starkey, W.G. and Richards, R.H. Phylogenetic and antigenic characterization of new fish nodavirusisolates from Europe and Asia. Virus Research 75, 59-67, 2001.
Stephan, J.S., Yeh, Y.Y., Ramachandran, V., Deminoff, S.J. and Herman, P.K. The Tor and cAMP-dependent protein kinase signaling pathways coordinately control autophagy in Saccharomyces cerevisiae. Autophagy 6, 294-295, 2010.
Strengert, M., Jennings, R., Davanture, S., Hayes, P. and Gabriel, G. Mucosal Reactive Oxygen Species Are Required for Antiviral Response: Role of Duox in Influenza A Virus Infection. Antioxidants and Redox Signaling 20, 2695-2709, 2013.
Su, Y. C., Hong, J. R. Betanodavirus B2 Causes ATP Depletion-induced Cell Death via Mitochondrial Targeting and Complex II Inhibition in Vitro and in Vivo. Journal of Biological Chemistry 285, 39801-39810, 2010.
Su, Y. C., Wu, J. L. and Hong, J. R. Betanodavirus up-regulates chaperone GRP78 via ER stress: roles of GRP78 in viral replication and hostmitochondria-mediated cell death. Apoptosis : An International Journal on Programmed Cell Death 16, 272-287, 2011.
Su, Y. C., Wu, J.L., Hong, J. R. Betanodavirus non-structural protein B2: A novel necrotic death factor that induces mitochondria-mediated cell death in fish cells. Virology 385, 143-154, 2009.
Suzuki, K. and Ohsumi, Y. Molecular machinery of autophagosome formation in yeast, Saccharomyces cerevisiae. Federation of European Biochemical Societies Letters 581, 2156-2161, 2007.
Talloczy, Z. Regulation of starvation- andvirus-induced autophagy by the eIF2alpha kinase signaling pathway. Proceedings of the National Academy of Sciences of the United States of America 99, 190-195 , 2002.
Tammy, T., Nguyen, Agnieszka, L., Choi, J. Y., Daniel, F., Markgraf, Mirco Junker, Mesut, B., Christer, S. E., Dennis, R. V., Tom, A. R. and Janet, M. S. Gem1 and ERMES Do Not Directly Affect Phosphatidylserine Transport from ER to Mitochondria or Mitochondrial Inheritance. Traffic 6, 880-890, 2012.
Tan, C., Huang, B., Chang, S.F., Ngoh, G.H., Munday, B. and Chen, S.C. Determination of the complete nucleotide sequences of RNA1 and RNA2 fromgreasy grouper (Epinephelus tauvina) nervous necrosis virus, Singapore strain.J. Journal of General Virology 82, 647-653, 2001.
Tanaka, T., Nogariya, O., Shionoiri, N., Maeda, Y. and Arakaki, A. Integrated molecular analysis of the inactivation of a non-enveloped virus, feline calicivirus, by UV-C radiation. Journal of Bioscience and Bioengineering 126, 63-68, 2018.
Thiery, R., Cozien, J., de Boisseson, C., Kerbart-Boscher, S. and Nevarez, L. Genomic classification of new betanodavirus isolates by phylogenetic analysis of the coat protein gene suggests a low host-fish species specificity. Journal of General Virology 85, 3079-3087, 2004.
Vural, F., Cebesoy, S. and Karakas, M. Classification of Cell Death. Journal of Entomology and Zoology Studies 5, 120-126, 2013.
Wang, K., Zhang, T., Dong, Q., Nice, E. C., Huang, C. and Wei, Y. Redox homeostasis: the linchpin in stem cell self-renewal and differentiation. Cell Death and Disease 4, 537, 2013.
Wei, Y., Pattingre, S., Sinha, S., Bassik, M. and Levine, B. JNK1-mediated phosphorylation of Bcl-2 regulates starvationinduced autophagy. Molecular Cell 30, 678-688, 2008.
Wesselborg, S. and Stork, S. Autophagy signal transduction by ATG proteins: from hierarchies to networks. Cellular and Molecular Life Sciences 72, 4721-4757, 2015.
Wong, J. Autophagosome supports coxsackievirus B3 replication in host cells. Journal of Virology 82, 9143-9153, 2008.
Wu, H. C., Chiu, C. S., Wu, J. L., Gong, H. Y., Chen, M. C., Lu, M. W. and Hong, J. R. Zebrafish anti-apoptotic protein zfBcl-X-L can block betanodavirus protein alpha-induced mitochondria-mediated secondary necrosis cell death. Fish and Shellfish Immunology 24, 436-449, 2008.
Yamamoto, K., Ichijo, H. and Korsmeyer, S. J. BCL-2 is phosphorylated and inactivated by an ASK1/Jun N-terminal protein kinase pathway normally activated at G (2)/M. Molecular and Cellular Biology 19, 8469-8478, 1999.
Yang, Q., Liu, T. T., Lin, H., Zhang, M., Wei, J., Luo, W. W., Hu, Y. H., Zhong, B., Hu, M. M. and Shu, H. B. TRIM32-TAX1BP1-dependent selective autophagic degradation of TRIF negatively regulates TLR3/4-mediated innate immune responses. Public Library of Science Pathology 13, e1006600, 2017.
Yang, Z. and Klionsky, D.J. Mammalian autophagy: core molecular machinery and signaling regulation. Current Opinion in Cell Biology 22, 124-131, 2010.
Yoshikoshi, K. and Inoue, K. Viral nervous necrosis in hatchery‐reared larvae and juveniles of Japanese parrotfish, Oplegnathus fasciatus (Temminck & Schlegel). Journal of Fish Diseases 13, 69-77, 1990.
Zou, S., Guo, J., Gao, R., Dong, L., Zhou, J., Zhang, Y., Dong, J., Bo, H., Qin, K. and Shu, Y. Inactivation of the novel avian influenza A (H7N9) virus under physical conditions or chemical agents treatment. Virology Journal 10, 289, 2013.

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