熱休克轉錄因子1為調節熱休克反應的主要因子，透過調控熱休克蛋白轉錄以進行修復因溫度及環境壓力受損的蛋白及抑制其變性。此研究首要完成點帶石斑魚熱休克轉錄因子1 (Orange-spotted grouper heat shock transcription factor 1，osgHSF1)的特性分析。兩種因選擇性剪切產生的新同形異構體同時被發現並命名為osgHSF1a和osgHSF1b。利用即時聚合酶鏈式反應分析，兩osgHSF1同形異構體廣泛表現於點帶石斑魚個組織中，並主要表現於大腦、眼睛和魚鰭中。而在溫度變化以及免疫刺激下，兩osgHSF1同形異構基因表現則呈現趨勢差異性。另一方面，大量表現osgHSF1於魚鰭細胞株會增加神經壞死病毒感染；而利用RNA干擾技術針對魚鰭細胞株HSF1進行抑制，細胞中神經壞死病毒量則隨之降低。此外，透過分析點帶石斑魚頭腎細胞在不同溫度下干擾素相關調節路徑中的重要抗病毒分子，如2C I-IFN、Mx1、Viperin和ISG15的基因表現變化進一步探討溫度效應於抗病毒反應的影響。結果顯示在聚肌胞苷酸或第一型干擾素重組蛋白刺激下，溫度可影響其誘導的抗病毒反應時間，其中低溫下則顯著增加抗病毒基因表現持續時間。綜合上述結果，osgHSF1同形異構基因在各種緊迫壓力下具差異性調控，同時參與於神經壞死病毒早期感染過程中。另一方面，環境溫度的影響則可調節點帶石斑魚受免疫刺激下抗病毒反應的時間。

Heat shock transcription factor 1 (HSF1) is the master regulator of the heat shock response and mediates the transcription of heat shock proteins (HSPs) that assist protein folding and inhibit protein denaturation in the presence of thermal and environmental stresses. This study firstly demonstrated the characterization of orange-spotted grouper HSF1 (osgHSF1). Two novel alternatively-spliced osgHSF1 isoforms were found and termed osgHSF1a and osgHSF1b. From the qPCR analysis, it showed that two osgHSF1 isoforms widely expressed in various tissues, especially the brain, eye and fin. Besides, it also showed differential expression of osgHSF1 isoforms in response to temperature changes and immune stimulations. On the other hand, the overexpression of osgHSF1 can enhance nervous necrosis virus (NNV) infection whereas the knockdown of it would reduce viral loads in grouper fin (GF-1) cells. In addition, the antiviral response in head kidney cells of orange-spotted grouper was investigated through evaluating antiviral molecules in IFN-regulated pathway, such as 2C I-IFN, Mx1, Viperin and ISG15 at different temperatures. The results showed that temperature can influence the patterns of the antiviral response along with the treatment of poly I:C or recombinant 2C I-IFN protein (r2C I-IFN), which low temperature could increase the period of antiviral gene expression significantly. Taken together, these studies demonstrated that osgHSF1 isoforms were differentially regulated by various stresses and involved in early NNV infection. Furthermore, environmental temperatures would modulate the period of antiviral responses in orange-spotted grouper.

Ainsworth, A. J., Dexiang, C., Waterstrat, P. R., and Greenway, T. Effect of temperature on the immune system of channel catfish (Ictalurus punctatus)-I. Leucocyte distribution and phagocyte function in the anterior kidney at 10 °C. Comparative Biochemistry and Physiology. Part A, Comparative Physiology 100, 907-912, 1991.

Airaksinen, S., Råbergh, C. M., Lahti, A., Kaatrasalo, A., Sistonen, L., and Nikinmaa, M. Stressor-dependent regulation of the heat shock response in zebrafish, Danio rerio. Comparative Biochemistry and Physiology. Part A, Molecular and Integrative Physiology 134, 839-846, 2003.

Akerfelt, M., Morimoto, R. I., and Sistonen, L. Heat shock factors: integrators of cell stress, development and lifespan. Nature Reviews. Molecular Cell Biology 11, 545-555, 2010.

Ali, A., Bharadwaj, S., O’Carroll, R., and Ovsenek, N. HSP90 interacts with and regulates the activity of heat shock factor 1 in Xenopus oocytes. Molecular and Cellular Biology 18, 4949-4960, 1998.

Alvarez-Torres, D., Bejar, J., Collet, B., Alonso, M. C., and Garcia-Rosado, E. Structural and functional characterization of the Senegalese sole (Solea senegalensis) Mx promoter. Fish and Shellfish Immunology 35, 1642-1648, 2013.

Amin, J., Ananthan, J., and Voellmy, R. Key features of heat shock regulatory elements. Molecular and Cellular Biology 8, 3761-3769, 1988.

Anckar, J., and Sistonen, L. Heat shock factor 1 as a coordinator of stress and developmental pathways. Advances in Experimental Medicine and Biology 594, 78-88, 2007.

Anckar, J., and Sistonen, L. Regulation of HSF1 function in the heat stress response: implications in aging and disease. Annual Review of Biochemistry 80, 1089-1115, 2011.

Arimoto, M., Maruyama, K., and Furusawa, I. Epizootiology of viral nervous necrosis (VNN) in striped jack. Fish Pathology 29, 19-24, 1994.

Arbuckle, J. L. Statistical Program for Social Sciences. Amos 23.0 User’s Guide, IBM SPSS, Chicago, 2014.

Avunje, S., Kim, W. S., Oh, M. J., Choi, I., and Jung, S. J. Temperature-dependent viral replication and antiviral apoptotic response in viral haemorrhagic septicaemia virus (VHSV)-infected olive flounder (Paralichthys olivaceus). Fish and Shellfish Immunology 32, 1162-1170, 2012.

Avunje, S., Oh, M. J., and Jung, S. J. Impaired TLR2 and TLR7 response in olive flounder infected with viral haemorrhagic septicaemia virus at host susceptible 15 oC but high at non-susceptible 20 oC. Fish and Shellfish Immunology 34, 1236-1243, 2013.

Baltimore, D. RNA-dependent DNA polymerase in virions of Rous sarcoma virus. Nature 226, 1, 1970.

Berryman, S., Brooks, E., Burman, A., Hawes, P., Roberts, R., Netherton, C., Monaghan, P., Whelband, M., Cottam, E., Elazar, Z., Jackson, T., and Wileman, T. 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.

Boltaña, S., Rey, S., Roher, N., Vargas, R., Huerta, M., Huntingford, F. A., Goetz, F. W, Moore, J., Garcia-Valtanen, P., Estepa, A., and Mackenzie, S. Behavioural fever is a synergic signal amplifying the innate immune response. Proceedings of the Royal Society B: Biological Sciences 280, 20131381, 2013.

Cerqueira, M., Rey, S., Silva, T., Featherstone, Z., Crumlish, M., and MacKenzie, S. Thermal preference predicts animal personality in Nile tilapia Oreochromis niloticus. Journal of Animal Ecology 85, 1389-1400, 2016.

Chen, N. C., Yoshimura, M., Guan, H. H., Wang, T. Y., Misumi, Y., Lin, C. C., Chuankhayan, P., Nakagawa, A., Chan, S. I., Tsukihara, T., Chen, T. Y., and Chen, C. J. Crystal structures of a piscine betanodavirus: mechanisms of capsid assembly and viral infection. PLoS Pathogens 11, e1005203, 2015.

Chen, Y. M., Kuo, C. E., Chen, G. R., Kao, Y. T., Zou, J., Secombes, C. J., and Chen, T. Y. Functional analysis of an orange-spotted grouper (Epinephelus coioides) interferon gene and characterisation of its expression in response to nodavirus infection. Developmental and Comparative Immunology 46, 117-128, 2014.

Chen, Y. M., Kuo, C. E., Lin, C. M., Shie, P. S., and Chen, T. Y. Cloning of crystallin from orange-spotted grouper and characterization of its activity as potential protective agent. Results in Immunology 1, 60-69, 2011.

Chen, Y. M., Su, Y. L., Shie, P. S., Huang, S. L., Yang, H. L., and Chen, T. Y. Grouper Mx confers resistance to nodavirus and interacts with coat protein. Developmental and Comparative Immunology 32, 825-836, 2008.

Chen, Y. M., Su, Y. L., Lin, J. H., Yang, H. L., and Chen, T. Y. Cloning of an orange-spotted grouper (Epinephelus coioides) Mx cDNA and characterisation of its expression in response to nodavirus. Fish and Shellfish Immunology 20, 58-71, 2006.

Chen, Y. M., Kuo, C. E., Wang, T. Y., Shie, P. S., Wang, W. C., Huang, S. L., Tsai, T. J., Chen, P. P., Chen, J. C. and Chen, T. Y. Cloning of an orange-spotted grouper Epinephelus coioides heat shock protein 90AB (HSP90AB) and characterization of its expression in response to nodavirus. Fish and Shellfish Immunology 28, 895-904, 2010.

Cheng, A. C., Cheng, S. A., Chen, Y. Y., and Chen, J. C. Effects of temperature change on the innate cellular and humoral immune responses of orange-spotted grouper Epinephelus coioides and its susceptibility to Vibrio alginolyticus. Fish and Shellfish Immunology 26, 768-772, 2009.

Chi, S. C., Hu, W. W., and Lo, B. J. Establishment and characterization of a continuous cell line (GF-1) derived from grouper, Epinephelus coioides (Hamilton): a cell line susceptible to grouper nervous necrosis virus (GNNV). Journal of Fish Diseases 22, 173-182, 1999a.

Chi, S. C., Lin, S. C., Su, H. M., and Hu, W. W. Temperature effect on nervous necrosis virus infection in grouper cell line and in grouper larvae. Virus Research 63, 107-114, 1999b.

Chu, B., Cates, S., Harris, A., Ohki, E. C., Tilkins, M. L., Price, P. J., and Ciccarone, V. C. Advanced transfection with Lipofectamine 2000 reagent: primary neurons, siRNA, and high-throughput applications. Methods 33, 95-103, 2004.

Collazos, M. E., Ortega, E., and Barriga, C. Effect of temperature on the immune system of a cyprinid fish (Tinca tinca L.). Blood phagocyte function at low temperature. Fish and Shellfish Immunology 4, 231-238, 1994.

Cooper, Z. A., Singh, I. S., and Hasday, J. D. Febrile range temperature represses TNF-alpha gene expression in LPS-stimulated macrophages by selectively blocking recruitment of Sp1 to the TNF-alpha promoter. Cell Stress and Chaperones 15, 665-673, 2010.

Conde, R., Belak, Z. R., Nair, M., O'Carroll, R. F., and Ovsenek, N. Modulation of Hsf1 activity by novobiocin and geldanamycin. Biochemistry and Cell Biology 87, 845-851, 2009.

Covert, J. B., and Reynolds, W. W. Survival value of fever in fish. Nature 267, 43-45, 1977.

Cui, M., Zhang, Q. Z., Yao, Z. J., and Zhang, Z. H. Molecular cloning and expression analysis of heat-shock protein 70 in orange-spotted grouper Epinephelus coioides following heat shock and Vibrio alginolyticus challenge. Journal of Fish Biology 79, 486-501, 2011.

De Silva, S. S., and Soto, D. Climate change and aquaculture: potential impacts, adaptation and mitigation. Climate Change Implications for Fisheries and Aquaculture: Overview of Current Scientific Knowledge, Food and Agriculture Organization, Rome, 151-212, 2009.

Desai, S., Liu, Z., Yao, J., Patel, N., Chen, J., Wu, Y., Ahn, E. E., Fodstad, O., and Tan, M. Heat shock factor 1 (HSF1) controls chemoresistance and autophagy through transcriptional regulation of autophagy-related protein 7 (ATG7). The Journal of Biological Chemistry 288, 9165-9176, 2013.

Di Cesare, S., Poccia, F., Mastino, A., and Colizzi, V. Surface expressed heat-shock proteins by stressed or human immunodeficiency virus (HIV)-infected lymphoid cells represent the target for antibody-dependent cellular cytotoxicity. Immunology 76, 341-343, 1992.

Ding, X. Z., Fernandez-Prada, C. M., Bhattacharjee, A. K., and Hoover, D. L. Over-expression of hsp-70 inhibits bacterial lipopolysaccharide-induced production of cytokines in human monocyte-derived macrophages. Cytokine 16, 210-219, 2001.

Dios, S., Romero, A., Chamorro, R., Figueras, A., and Novoa, B. Effect of the temperature during antiviral immune response ontogeny in teleosts. Fish and Shellfish Immunology 29, 1019-1027, 2010.

Dittmar, J., Janssen, H., Kuske, A., Kurtz, J., and Scharsack, J. P. Heat and immunity: an experimental heat wave alters immune functions in three-spined sticklebacks (Gasterosteus aculeatus). Journal of Animal Ecology 83, 744-757, 2014.

Duarte, C. M., Marbá, N., and Holmer, M. Rapid domestication of marine species. Science 316, 382-383, 2007.

Dyer, S. D., Dickson, K. L., Zimmerman, E. G., and Sanders, B. M. Tissue-specific patterns of synthesis of heat-shock proteins and thermal tolerance of the fathead minnow (Pimephales promelas). Canadian Journal of Zoology 69, 2021-2027, 1991.

Elbashir, S. M., Harborth, J., Lendeckel, W., and Yalcin, A. Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature 411, 494-498, 2001.

Ellis, A. E. Innate host defence mechanisms of fish against viruses and bacteria. Developmental and Comparative Immunology 25, 827-839, 2001.

Evans, S. S., Repasky, E. A., and Fisher, D. T. Fever and the thermal regulation of immunity: the immune system feels the heat. Nature Reviews Immunology 15, 335-349, 2015.

Evans, T. G., Belak, Z., Ovsenek, N., and Krone, P. H. Heat shock factor 1 is required for constitutive Hsp70 expression and normal lens development in embryonic zebrafish. Comparative Biochemistry and Physiology. Part A, Molecular and Integrative Physiology 146, 131-140, 2005.

Felgner, P. L., Gadek, T. R., Holm, M., Roman, R., Chan, H. W., Wenz, M., and Danielsen, M. Lipofection: a highly efficient, lipid-mediated DNA-transfection procedure. Proceedings of the National Academy of Sciences of the United States of America 84, 7413-7417, 1987.

Fenner, B. J., Thiagarajan, R., Chua, H. K., and Kwang, J. Betanodavirus B2 is an RNA interference antagonist that facilitates intracellular viral RNA accumulation. Journal of Virology 80, 85-94, 2006.

Filone, C. M., Caballero, I. S., Dower, K., Mendillo, M. L., Cowley, G. S., Santagata, S., Rozelle, D. K., Yen, J., Rubins, K. H., Hacohen, N., Root, D. E., Hensley, L. E., and Connor, J. The master regulator of the cellular stress response (HSF1) is critical for orthopoxvirus infection. PLoS Pathogens 10, e1003904, 2014.

Fiorenza, M. T., Farkas, T., Dissing, M., Kolding, D., and Zimarino, V. Complex expression of murine heat shock transcription factors. Nucleic Acids Research 23, 467-474, 1995.

Fujikake, N., Nagai, Y., Popiel, H. A., Kano, H., Yamaguchi, M., and Toda, T. Alternative splicing regulates the transcriptional activity of Drosophila heat shock transcription factor in response to heat/cold stress. Federation of European Biochemical Societies Letters 579, 3842-3848, 2005.

Fujimoto, M., and Nakai, A. The heat shock factor family and adaptation to proteotoxic stress. Federation of European Biochemical Societies Journal 277, 4112-4125, 2010a.

Fujimoto, M., Hayashida, N., Katoh, T., Oshima, K., Shinkawa, T., Prakasama, R., Tan, K., Inouye, S., Takii, R., and Nakai, A. A novel mouse HSF3 has the potential to activate nonclassical heat-shock genes during heat shock. Molecular Biology of the Cell 21, 106-116, 2010b.

Fujimoto, M., Oshima, K., Shinkawa, T., Wang, B. B., Inouye, S., Hayashida, N., Takii, R., and Nakai, A. Analysis of HSF4 binding regions reveals its necessity for gene regulation during development and heat shock response in mouse lenses. The Journal of Biological Chemistry 283, 29961-29970, 2008.

Fukuda, Y., Nguyen, H. D., Furuhashi, M., and Nakai, T. Mass mortality of cultured sevenband grouper, Epinephelus septemfasciatus, associated with viral nervous necrosis. Fish Pathology 31, 165-170, 1996.

Gasteiger, E., Gattiker, A., Hoogland, C., Ivanyi, I., Appel, R. D., and Bairoch, A. ExPASy: the proteomics server for in-depth protein knowledge and analysis. Nucleic Acids Research 31, 3784-3788, 2003.

Gillooly, J. F., Brown, J. H., West, G. B., Savage, V. M., and Charnov, E. L. Effects of size and temperature on metabolic rate. Science 293, 2248-2251, 2001.

Glotzer, J. B., Saltik, M., Chiocca, S., Michou, A. I., Moseley, P., and Cotton, M. Activation of heat-shock response by an adenovirus is essential for virus replication. Nature 407, 207-211, 2000.

Gould, S. J., and Subramani, S. Firefly luciferase as a tool in molecular and cell biology. Analytical Biochemistry 175, 5-13, 1988.

Guisbert, E., Czyz, D. M., Richter, K., McMullen, P. D., and Morimoto, R. I. Identification of a tissue-selective heat shock response regulatory network. PLoS Genetics 9, e1003466, 2013.

Hamilton, A. J., and Baulcombe, D. C. A species of small antisense RNA in posttranscriptional gene silencing in plants. Science 286, 950-952, 1999.

Hanahan, D. Studies on transformation of Escherichia coli with plasmids. Journal of Molecular Biology 166, 557-580, 1983.

Hardie, L. J., Fletcher, T. C., and Secombes, C. J. Effect of temperature on macrophage activation and the production of macrophage activating factor by rainbow trout (Oncorhynchus mykiss) leucocytes. Developmental and Comparative Immunology 18, 57-66, 1994.

Hartl, F. U., and Hayer-Hartl, M. Molecular chaperones in the cytosol:from nascent chain to folded protein. Science 295, 1852-1858, 2002.

Hasday, J. D., and Singh, I. S. Fever and the heat shock response: distinct, partially overlapping processes. Cell Stress Chaperones 5, 471-480, 2000.

Hata, N., Okinaka,Y., Iwamoto, T., Kawato, Y., Mori, K., and Nakai, T. Identification of RNA regions that determine temperature sensitivities in betanodaviruses. Archives of Virology 155, 1597-1606, 2010.

Heemstra, P. C., and Randall, J. E. Grouper of the world. FAO Species Catalogue, Food and Agriculture Organization, Rome, 172-175, 1993.

Hofmann, K., and Baron, M. D. Pretty printing and shading of multiple-alignment files. Boxshade Version 3.21, Bioinformatics Group, Switzerland, 1996.

Honda, K., Takaoka, A., and Taniguchi, T. Type I interferon gene induction by the interferon regulatory factor family of transcription factors. Immunity 25, 349-360, 2006

Hori, T. S., Gamperl, A. K., Booman, M., Nash, G. W., and Rise, M. L. A moderate increase in ambient temperature modulates the Atlantic cod (Gadus morhua) spleen transcriptome response to intraperitoneal viral mimic injection. Biomed Central Genomics 13, 431, 2012.

Huang, X., Huang, Y., Cai, J., Wei, S., Ouyang, Z., and Qin, Q. Molecular cloning, expression and functional analysis of ISG15 in orange-spotted grouper, Epinephelus coioides. Fish and Shellfish Immunology 34, 1094-1102, 2013.

Huang, Y., Cai, X., Zou, Z., Wang, S., Wang, G., Wang, Y., and Zhang, Z. Molecular cloning, characterization and expression analysis of three heat shock responsive genes from Haliotis diversicolor. Fish and Shellfish Immunology 36, 590-599, 2013.

Inkpen, S. M., Hori, T. S., Gamperl, A. K., Nash, G. W., and Rise, M. L. Characterization and expression analyses of five interferon regulatory factor transcripts (Irf4a, Irf4b, Irf7, Irf8, Irf10) in Atlantic cod (Gadus morhua). Fish and Shellfish Immunology 44, 365-381, 2015.

Inouye, S., Izu, H., Takaki, E., Suzuki, H., Shirai, M., Yokota, Y., Ichikawa, H., Fujimoto, M., and Nakai, A. Impaired IgG production in mice deficient for heat shock transcription factor 1. The Journal of Biological Chemistry 279, 38701-38709, 2004.

Ishii, Y. Electron microscopic visualization of autophagosomes induced by infection of human papillomavirus pseudovirions. Biochemical and Biophysical Research Communications 433, 385-389, 2013.

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.

Iwamoto, T., Mise, K., Mori, K., Arimoto, M., Nakai, T., and Okuno, T. Establishment of an infectious RNA transcription system for Striped jack nervous necrosis virus, the type species of the betanodaviruses. Journal of General Virology 82, 2653-2662, 2001.

Kawabe, S., and Yokoyama, Y. Novel isoforms of heat shock transcription factor 1 are induced by hypoxia in the Pacific oyster Crassostrea gigas. Journal of Experimental Zoology Part A: Ecological and Integrative Physiology 315, 394-407, 2011.

Kim, C. S., Kim, W. S., Nishizawa, T., and Oh, M. J. Prevalence of viral nervous necrosis (VNN) in sevenband grouper, Epinephelus septemfasciatus farms. Journal of Fish Pathology 25, 111-116, 2012

Kim, S. S., Chang, Z., and Park, J. S. Identification, tissue distribution and characterization of two heat shock factors (HSFs) in goldfish (Carassius auratus). Fish and Shellfish Immunology 43, 375-386, 2015.

Kiryu, I., de la Pen˜a, L. D., and Maeno, Y. Distribution of nervous necrosis virus in orange-spotted grouper Epinephelus coioides with asymptomatic infection. Fish Pathology 42, 163-165, 2007.

Krone, P. H., Lele, Z., and Sass, J. B. Heat shock genes and the heat shock response in zebrafish embryos. Biochemistry and Cell Biology 75, 487-497, 1997.

Kuo, H. C., Wang, T. Y., Chen, P. P., Chen, Y. M., Chuang, H. C., and Chen, T. Y. Real-time quantitative PCR assay for monitoring of nervous necrosis virus infection in grouper aquaculture. Journal of Clinical Microbiology 49, 1090-1096, 2011.

Kuo, H. C., Wang, T. Y., Hsu, H. H., Chen, P. P., Lee, S. H., Chen, Y. M., Tsai, T. J., Wang, C. K., Ku, H. T., Lee, G. B., and Chen, T. Y. Nervous necrosis virus replicates following the embryo development and dual infection with iridovirus at juvenile stage in grouper. PLoS One 7, e36183, 2012.

Letunic, I., Doerks, T., and Bork, P. SMART: recent updates, new developments and status in 2015. Nucleic Acids Research 43, 257-260, 2015.

Liang, T. J. RNA interference functions as an antiviral immunity mechanism in mammals. Nature Medicine 19, 869-878, 2013.

Lin, X., Xie, S., Su, Y., and Cui, Y. Optimum temperature for the growth performance of juvenile orange-spotted grouper (Epinephelus coioides H.). Chinese Journal of Oceanology and Limnology 26, 69-75, 2008.

Lu, R., Maduro, M., Li, F., Li, H. W., Broitman-Maduro, G., Li, W. X., and Ding, S. W. Animal virus replication and RNAi-mediated antiviral silencing in Caenorhabditis elegans. Nature 436, 1040-1043, 2005.

Magnadóttir, B. Innate immunity of fish (overview). Fish and Shellfish Immunology 20, 137-151, 2006.

Magnadóttir, B., Jónsdóttir, H., Helgason, S., Björnsson, B., Jørgensen, TØ., and Pilström, L. Humoral immune parameters in Atlantic cod (Gadus morhua L.): I. The effects of environmental temperature. Comparative Biochemistry and Physiology. Part B, Biochemistry and Molecular Biology 122, 173-180, 1999.

Mahmood, H., Staehelin, T., and Gordon, J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proceedings of the National Academy of Sciences of the United States of America 76, 4350-4354, 1979.

Mahmood, T., and Yang, P. C. Western blot: technique, theory, and trouble shooting. North American Journal of Medical Sciences 4, 429, 2012.

Makrinos, D. L., and Bowden, T. J. Natural environmental impacts on teleost immune function. Fish and Shellfish Immunology 53, 50-57, 2016.

Mandel, M., and Higa, A. Calcium-dependent bacteriophage DNA infection. Journal of Molecular Biology 53, 159-162, 1970.

Mannige, R. V. and Brooks, C. L. Periodic table of virus capsids: implications for natural selection and design. PloS One 5, e9423, 2010.

McMillan, D. R., Christians, E., Forster, M., Xiao, X., Connell, P., Plumier, J. C., Zuo, X., Richardson, J., Morgan, S., and Benjamin, I. J. Heat shock transcription factor 2 is not essential for embryonic development, fertility, or adult cognitive and psychomotor function in mice. Molecular Biology of the Cell 22, 8005-8014, 2002.

Mercier, P. A., Winegarden, N. A. and Westwood, J. T. Human heat shock factor 1 is predominantly a nuclear protein before and after heat stress. Journal of Cell Science 112, 2765-2774, 1999.

Mignatti, A., Boag, B., and Cattadori, I. M. Host immunity shapes the impact of climate changes on the dynamics of parasite infections. Proceedings of the National Academy of Science of the United States of America 113, 2970-2975, 2016.

Mori, K., Nakai, T., Muroga, K., Arimoto, M., Mushiakc, K., and Furuswa, I. Properties of a new virus belong to Nodaviridae found in larval striped jack (Pseudocaranx dentex) with nervous necrosis. Virology 187, 378-381, 1992.

Morimoto, R. I. Regulation of the heat shock transcriptional response: cross talk between a family of heat shock factors, molecular chaperones, and negative regulators. Genes and Development 12, 3788-3796, 1998.

Moseley, P. L. Heat shock proteins and heat adaptation of the whole organism. Journal of Applied Physiology 83, 1413-1417, 1997.

Munday, B. L., and Nakai, T. Nodaviruses as pathogens in larval and juvenile marine fin fish. World Journal of Microbiology and Biotechnology 13, 375-381, 1997.

Munday, B. L., Kwang, J., and Moody, N. Betanodavirus infections of teleost fish: a review. Journal of Fish Diseases 25, 127-142, 2002.

Murapa, P., Gandhapudi, S., Skaggs, H. S., Sarge, K. D., and Woodward, J. G. Physiological fever temperature induces a protective stress response in T lymphocytes mediated by heat shock factor-1 (HSF1). The Journal of Immunology 179, 8305-8312, 2007.

Nakai, A. Molecular basis of HSF regulation. Nature Structural and Molecular Biology 23, 93-95, 2016

Neef, D. W., Turski, M. L., and Thiele, D. J. Modulation of heat shock transcription factor 1 as a therapeutic target for small molecule intervention in neurodegenerative disease. PLoS Biology 8, e1000291, 2010.

Neudegger, T., Verghese, J., Hayer-Hartl, M., Hartl, F. U., and Bracher, A. Structure of human heat-shock transcription factor 1 in complex with DNA. Nature Structural and Molecular Biology 23, 140-146, 2016.

Neueder, A., Achilli, F., Moussaoui, S., and Bates, G. P. Novel isoforms of heat shock transcription factor 1, HSF1γα and HSF1γβ, regulate chaperone protein gene transcription. The Journal of Biological Chemistry 289, 19894-19906, 2014.

Nguyen, V. T., Morange, M., and Bensaude, O. Firefly luciferase luminescence assays using scintillation counters for quantitation in transfected mammalian cells. Analytical Biochemistry 171, 404-408, 1988.

Nolan, T., Hands, R. E., and Bustin, S. A. Quantification of mRNA using real-time RT-PCR. Nature Protocols 1, 1559-1582, 2006.

Ojima, N., and Yamashita, M. Cloning and characterization of two distinct isoforms of rainbow trout heat shock factor 1. Evidence for heterotrimer formation. European Journal of Biochemistry 271, 703-712, 2004.

Ou, M. C., Chen, Y. M., Jeng, M. F., Chu, C. J., Yang, H. L., and Chen, T. Y. Identification of critical residues in nervous necrosis virus B2 for dsRNA-binding and RNAi-inhibiting activity through by bioinformatic analysis and mutagenesis. Biochemical and Biophysical Research Communications 361, 634-640, 2007.

Panzarin, V., Toffan, A., Abbadi, M., Buratin, A., Mancin, M., Braaen, S., Olsen, C. M., Bargelloni, L., Rimstad, E., and Cattoli, G. Molecular basis for antigenic diversity of genus betanodavirus. PLoS One 11, e0158814, 2016.

Pelham, H. R. B. A regulatory upstream promoter element in the Drosophila hsp70 heat-shock gene. Cell 30, 517-528, 1982.

Pettersen, E. F., Bjørløw, I., Hagland, T. J., and Wergeland, H. I. Effect of seawater temperature on leucocyte populations in Atlantic salmon post-smolts. Veterinary Immunology and Immunopathology 106, 65-76, 2005.

Pierre, S., Gaillard, S., Prevot-D’Alvise, N., Aubert, J., Rostaing-Capaillon, O., Leung-Tack, D., and Grillasca, J. P. Grouper aquaculture: Asian success and Mediterranean trials. Aquatic Conservation: Marine and Freshwater Ecosystems 18, 297-308, 2008.

Pirkkala, L., Nykänen, P., and Sistonen, L. Roles of the heat shock transcription factors in regulation of the heat shock response and beyond. The Federation of American Societies for Experimental Biology Journal 15, 1118-1131, 2001.

Poynter, S. J., and DeWitte-Orr, S. J. Fish interferon-stimulated genes: The antiviral effectors. Developmental and Comparative Immunology 65, 218-225, 2016.

Råbergh, C. M., Airaksinen, S., Soitamo, A., Björklund, H. V., Johansson, T., Nikinmaa, M., and Sistonen, L. Tissue-specific expression of zebrafish (Danio rerio) heat shock factor 1 mRNAs in response to heat stress. Journal of Experimental Biology 203, 1817-1824, 2000.

Rabindran, S. K., Giorgi, G., Clos, J., and Wu, C. Molecular cloning and expression of a human heat shock factor, HSF1. Proceedings of the National Academy of Science of the United States of America 88, 6906-6910, 1991.

Rabindran, S. K., Haroun, R. I., Clos, J., Wisniewski, J., and Wu, C. Regulation of heat shock factor trimer formation: role of a conserved leucine zipper. Science 259, 230-234, 1993.

Rawat, P., and Mitra, D. Cellular heat shock factor 1 positively regulates human immunodeficiency virus-1 gene expression and replication by two distinct pathways. Nucleic Acids Research 39, 5879-5892, 2011.

Rey, S., Moiche, V., Boltaña, S., Teles, M., and MacKenzie, S. Behavioural fever in zebrafish larvae. Developmental and Comparative Immunology 67, 287-292, 2017.

Reynolds, W. W., Casterlin, M. E., and Covert, J. B. Febrile responses of bluegill (Lepomis macrochirus) to bacterial pyrogens. Journal of Thermal Biology 3, 129-130, 1978.

Richter, K., Haslbeck, M., and Buchner, J. The heat shock response: life on the verge of death. Molecular Cell 40, 253-266, 2010.

Rijkers, G. T., Frederix-Wolters, E. M., and van Muiswinkel, W. B. The immune system of cyprinid fish. Kinetics and temperature dependence of antibody-producing cells in carp (Cyprinus carpio). Immunology 41, 91-97, 1980.

Sarge, K. D., Zimarino, V., Holm, K., Wu, C., and Morimoto, R. I. Cloning and characterization of two mouse heat shock factors with distinct inducible and constitutive DNA-binding ability. Genes and Development 5, 1902-1911, 1991.

Schneider, W. M, Chevillotte, M. D., and Rice, C. M. Interferon-stimulated genes: a complex web of host defenses. Annual Review of Immunology 32, 513-545, 2014.

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, Y., Mosser, D. D., and Morimoto, R. I. Molecular chaperones as HSF1-specific transcriptional repressors. Genes and Development 12, 654-666, 1998.

Singh, I. S., He, J. R., Hester, L., Fenton, M. J., and Hasday, J. D. Bacterial endotoxin modifies heat shock factor-1 activity in RAW 264.7 cells: implications for TNF-alpha regulation during exposure to febrile range temperatures. Journal of Endotoxin Research 10, 175-184, 2004.

Singh, V., and Aballay, A. Heat shock and genetic activation of HSF-1 enhance immunity to bacteria. Cell Cycle 5, 2443-2446, 2006.

Sinyakov, M. S., Dror, M., Zhevelev, H. M., Margel, S., and Avtalion, R. R. Natural antibodies and their significance in active immunization and protection against a defined pathogen in fish. Vaccine 20, 3668-3674, 2002.

Song, M., Pinsky, M. R., and Kellum, J. A. Heat shock factor 1 inhibits nuclear factor-κB nuclear binding activity during endotoxin tolerance and heat shock. Journal of Critical Care 23, 406-415, 2008.

Sorger, P. K., and Nelson, H. C. Trimerization of a yeast transcriptional activator via a coiled-coil motif. Cell 59, 807-813, 1989.

Stetter, K. O. Hyperthermophiles in the history of life. Philosophical transactions of the Royal Society of London. Series B, Biological sciences 361, 1837-1842, 2006.

Takaki, E., Fujimoto, M., Sugahara, K., Nakahari, T., Yonemura, S., Tanaka, Y., Hayashida, N., Inouye, S., Takemoto, T., Yamashita, H., and Nakai, A. Maintenance of olfactory neurogenesis requires HSF1, a major heat shock transcription factor in mice. The Journal of Biological Chemistry 281, 4931-4937, 2006.

Tanaka, S., Aoki, H., and Nakai, T. Pathogenicity of the nodavirus detected from diseased sevenband grouper Epinephelus septemfasciatus. Fish Pathology 33, 31-36, 1998.

Thanasaksiri, K., Sakai, N., Yamashita, H., Hirono, I., and Kondo, H. Influence of temperature on Mx gene expression profiles and the protection of sevenband grouper, Epinephelus septemfasciatus, against red-spotted grouper nervous necrosis virus (RGNNV) infection after poly (I:C) injection. Fish and Shellfish Immunology 40, 441-445, 2014.

Verbeke, P., Fonager, J., Clark, B. F. C., and Rattan, S. I. S. Heat shock response and ageing: mechanisms and applications. Cell Biology International 25, 845-857, 2001.

Vihervaara, A., Sergelius, C., Vasara, J., Blom, M. A., Elsing, A. N., Roos-Mattjus, P, and Sistonen, L. Transcriptional response to stress in the dynamic chromatin environment of cycling and mitotic cells. Proceedings of the National Academy of Sciences of the United States of America 110, 3388-3397, 2013.

Walsh, D., Li, Z., Wu, Y., and Nagata, K. Heat shock and the role of the HSPs during neural plate induction in early mammalian CNS and brain development. Cellular and Molecular Life Sciences 53, 198-211, 1997.

Wilfinger, W. W., Mackey, K., and Chomczynski, P. Effect of pH and ionic strength on the spectrophotometric assessment of nucleic acid purity. Biotechniques 22, 474-476, 1997.

Wu, C. S., Wang, T. Y., Liu, C. F., Lin, H. P., Chen, Y. M., and Chen, T. Y. Molecular cloning and characterization of orange-spotted grouper (Epinephelus coioides) CXC chemokine ligand 12. Fish and Shellfish Immunology 47, 996-1005, 2015

Xiao, X., Zuo, X., Davis, A. A., McMillan, D. R., Curry, B. B., Richardson, J. A., and Benjamin, I. J. HSF1 is required for extra-embryonic development, postnatal growth and protection during inflammatory responses in mice. The European Molecular Biology Organization Journal 18, 5943-5952, 1999.

Xie, Y., Chen, C., Stevenson, M. A., Auron, P. E., and Calderwood, S. K. Heat shock factor 1 represses transcription of the IL-1 beta gene through physical interaction with the nuclear factor of interleukin 6. The Journal of Biological Chemistry 277, 11802-11810, 2002.

Xu, G., Sheng, X., Xing, J., and Zhan, W. Effect of temperature on immune response of Japanese flounder (Paralichthys olivaceus) to inactivated lymphocystis disease virus (LCDV). Fish and Shellfish Immunology 30, 525-531, 2011.

Yabu, T., Imamura, S., Mohammed, M. S., Touhata, K., Minami, T., Terayama, M., and Yamashita, M. Differential gene expression of HSC70/HSP70 in yellowtail cells in response to chaperone-mediated autophagy. The Federation of European Biochemical Societies Journal 278, 673-685, 2011.

Yamashita, H., Fujita, Y., Kawakami, H., and Nakai, T. The efficacy of inactivated virus vaccine against viral nervous necrosis (VNN). Fish Pathology 40, 15-21, 2005.

Yamashita, M., Yabu, T., and Ojima, N. Stress Protein HSP70 in Fish. Aqua-BioScience Monographs 3, 111-141, 2010.

Yan, H., Zhang, S., Li, X. Y., Yuan, F. H., Qiu, W., Chen, Y. G., Weng, S. P., He, J. G., and Chen, Y. H. Identification and functional characterization of heat shock transcription factor1 in Litopenaeus vannamei. Fish and Shellfish Immunology 37, 184-192, 2014.

Yoon, Y. J., Kim, J. A., Shin, K. D., Shin, D. S., Han, Y. M., Lee, Y. J., Kwon, B. M., and Han, D. C. KRIBB11 inhibits HSP70 synthesis through inhibition of heat shock factor 1 function by impairing the recruitment of positive transcription elongation factor b to the hsp70 promoter. The Journal of Biological Chemistry 286, 1737-1747, 2010.

Zou, J., Guo, Y., Guettouche, T., Smith, D. F., and Voellmy, R. Repression of heat shock transcription factor HSF1 activation by HSP90 (HSP90 complex) that forms a stress-sensitive complex with HSF1. Cell 94, 471-480, 1998.

Zuo, J., Baler, R., Dahl, G., and Voellmy, R. Activation of the DNA binding ability of human heat shock transcription factor 1 may involve the transition from an intramolecular to an intermolecular triple-stranded coiled-coil structure. Molecular and Cellular Biology 14, 7557-7568, 1994.