傳染性脾腎壞死病毒 (ISKNV)屬於虹彩病毒科巨細胞病毒屬，主要感染魚之腎臟及脾臟。近年來透過水產品貿易，傳播到各個國家，造成水產養殖的嚴重損失。虹彩病毒透過絲胺酸/蘇胺酸激酶 (Serine/threonine kinase, ST kinase)誘導石斑魚鰭細胞株之凋亡。本研究比對ISKNV ST kinase之基因序列。結果顯示該基因在巨細胞病毒是特有之序列。透過建立ISKNV ST kinase蛋白序列之預測模型，可以發現磷酸化酶激酶相似之區域。故推測ST激酶蛋白的功能可能影響細胞之磷酸化作用。
本研究以shRNA抑制ST kinase，並建立穩定表達shRNA之sh58細胞株。藉由sh58細胞株和對照組在感染ISKNV後之差異，觀察到ISKNV的ST kinase透過磷酸化p53 Ser392位點，正調控凋亡蛋白上調，進而活化caspase 9/3導致細胞凋亡。ST kinase亦會促進AMPK之磷酸化，進而抑制mTOR活化，並增加ULK1 Ser555之磷酸化導致細胞自噬。免疫共沉澱測定結果證實，ST kinase可能直接作用於p53作為受質。
ISKNV之ST kinase調節細胞信號通路及蛋白磷酸化影響細胞存亡，是防治病毒的重要靶點。研究ST kinase的磷酸化模式，為今後預防或治療ISKNV感染提供研究依據。

Infectious splenorenal necrosis virus (ISKNV) belongs to the genus Megalocytivirus of the family Iridoviridae and mainly infects the kidneys and spleens of fish. In recent years, it has spread to various countries through aquatic product trade, causing severe losses to aquaculture. Iridovirus induces apoptosis in grouper fin cell lines through serine/threonine kinase (ST kinase). This study compared the gene sequence of ISKNV ST kinase. The results showed that this gene is a unique sequence in cytomegalovirus.
This study used shRNA to inhibit ST kinase and establish a sh58 cell line stably expressing shRNA. Based on the difference between the sh58 cell line and the control group after infection with ISKNV, it was observed that the ST kinase of ISKNV induces the upregulation of pro-apoptotic proteins by phosphorylating the p53 Ser392 site leading to cell apoptosis. ST kinase promotes the activation of the autophagy pathway by increasing the phosphorylation of ULK1 Ser555. Co-immunoprecipitation assay results indicate that ST kinase may directly use p53 as a substrate.
The ST kinase of ISKNV, a key regulator of cell signaling pathways and protein phosphorylation, is a prime target for virus prevention and treatment. Our understanding of the phosphorylation pattern of ST kinase could serve as a robust research foundation for future endeavors to combat ISKNV infection.

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