title: ISAV infection promotes apoptosis of SHK-1 cells through a ROS/p38 MAPK/Bad signaling pathway.
abstract: The impact that the infectious salmon anemia virus (ISAV) has on the immune response of Salmo salar, from the perspective of activating/inactivating cellular processes, is currently unknown. Therefore, the present study evaluated this interaction and found that SHK-1 cells infected with ISAV resulted in respiratory burst activation and the induction of a strong pro-apoptotic imbalance through an increased expression of the Bad protein and decreased transcripts of Bcl-xl. Interestingly, the pharmacological inhibition of the p38 MAPK protein through SB203580 blocked the production of reactive oxygen species, the activity of caspase 3, and the formation of apoptotic nuclei in SHK-1 cells. Additionally, when the NADPH oxidase complex, a producer of superoxide anions, was blocked through apocynin, decreased apoptotic activity was observed in infected cells without significant modifications to viral amplification. These results, together with bioinformatics analysis performed for the Bad gene of fugu, suggest that the ISA virus triggers a strong production of oxygen radicals capable of activating transduction signaling pathways and mediating the expression and activation of pro-apoptotic proteins through the p38 MAPK pathway, all of which results in the apoptosis of ISAV infected cells.
authors.affiliation: Facultad de Ciencias, Instituto de Bioquímica y Microbiología, Universidad Austral de Chile, Campus Isla Teja S/N, Valdivia, Chile. Electronic address: volavarria@uach.cl.
authors.forename: Víctor H
authors.initials: VH
authors.lastname: Olavarría
authors.affiliation: Facultad de Ciencias, Instituto de Bioquímica y Microbiología, Universidad Austral de Chile, Campus Isla Teja S/N, Valdivia, Chile.
authors.forename: Pablo
authors.initials: P
authors.lastname: Recabarren
authors.affiliation: Facultad de Ciencias, Instituto de Bioquímica y Microbiología, Universidad Austral de Chile, Campus Isla Teja S/N, Valdivia, Chile.
authors.forename: Fernanda
authors.initials: F
authors.lastname: Fredericksen
authors.affiliation: Facultad de Ciencias, Instituto de Bioquímica y Microbiología, Universidad Austral de Chile, Campus Isla Teja S/N, Valdivia, Chile.
authors.forename: Melina
authors.initials: M
authors.lastname: Villalba
authors.affiliation: Facultad de Ciencias, Instituto de Bioquímica y Microbiología, Universidad Austral de Chile, Campus Isla Teja S/N, Valdivia, Chile; Interdisciplinary Center for Aquaculture Research (INCAR), Víctor Lamas 1290, PO Box 160-C, Concepción, Chile. Electronic address: ayanez@uach.cl.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Yáñez
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D002460:Cell Line; D060226:Head Kidney / Q000201:enzymology / Q000473:pathology / Q000821:virology*; D046829:Isavirus / Q000502:physiology*; D008954:Models, Biological; D008969:Molecular Sequence Data; D009976:Orthomyxoviridae Infections / Q000201:enzymology* / Q000821:virology; D011401:Promoter Regions, Genetic / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism*; D020317:Salmo salar; D015398:Signal Transduction; D051025:bcl-Associated Death Protein / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D017382:Reactive Oxygen Species; D051025:bcl-Associated Death Protein; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Apoptosis; ISA virus; NADPH; Oxidative stress; Reactive oxygen species (ROS); p38 MAPK