當前主要危害台灣養殖業的水產病毒以虹彩病毒和神經壞死病毒為主，而傳染性脾臟及腎臟壞死病毒（ISKNV）屬於虹彩病毒科-巨大細胞屬病毒，主要感染脾臟和腎臟，導致器官腫脹，使魚隻死亡，因此需要了解虹彩病毒的機轉和防治方法，解決病毒感染問題。自噬作用是細胞內進行分解回收胞器或不需要的蛋白，並且再利用的一種重要生理機制，在作用時，細胞內會形成囊狀構造，將這些不需要的物質包覆起來，形成自噬體（autophagosome），接著與溶酶體（lysosome）融合，將包裹的物質分解，並提供給其他細胞再利用這些成分。利用ISKNV感染石斑魚鰭細胞（GF-1），在先前的實驗中發現在感染ISKNV後第2天，自噬作用的指標LC3-II表現量上升，因此我們試著探討ISKNV在魚類細胞對自噬作用與宿主細胞產生的影響。本文在感染ISKNV後，發現病毒藉由調控，Akt/ULK1訊號傳遞路徑誘導細胞自噬發生；並在添加Akt抑制劑至受感染ISKNV的GF-1細胞後，則發現自噬作用停止在晚期階段的分解時期，並且有許多小顆的自噬溶酶體形成，聚集在一起的現象，形成巨大的自噬溶酶體（huge autolysosome），並且使病毒的蛋白質表現量減少，促使細胞存活率更加提升。而mTOR在本系統中可能不參與細胞自噬，與細胞生長、存活較相關。

Infectious spleen and kidney necrosis virus （ISKNV）mainly infects the spleen and kidney, leading to organs swelling and fish died. We need to understand the machine of iridovirus and control methods to solve the virus infection. In this present, we examined that iridovirus-ISKNV induced autophagy process and its possible signaling pathway related to Akt/mTOR activation.
Autophagy is an important physiological mechanism in the cell that it degraded and recycled unwanted protein or broken organelles. However, control of autophagy process is advantaged or disadvantaged for virus replication or viral expression is still very few to know especially megalocytivirus.
In our system, in ISKNV induced autophagy in GF-1 cells, we found that the expression level of autophagy marker LC3-II increased by western blot analysis at 24 h and 48 hpi. Then, further confirmed by RFP-LC3-II reporting system and combined with autophagy tracing dye （monodansylcadaverine, MDC） on late autophagosome, which received a consistent result. Furthermore, in the molecular autophagy pathway, we have screened and focused on Akt/UKL1 signaling pathway. In the study Akt specific inhibitor MK-2206-HCl was used to test the effect of Akt/UKL1 signaling. In the MK-2206-HCl treatment, p-Akt Ser 473 was inhibited and increased p-UKL1 757, finally promoted autophagic process. In our observation, MK2206 not olny enhanced host cell survival at 3 day post-infection but also reduced ISKNV major capsid protein（MCP）. Our data may suggest that first report ISKNV induced autophagy process could be modulated by Akt specific inhibitor on enhanced host viability, which may provide new insight into DNA virus infection and disease controlling.

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