白點症病毒（white spot syndrome virus，WSSV）近年來造成蝦類養殖產業經濟重大損失，因此了解其致病機轉日趨重要。先前實驗室研究發現WSSV感染白蝦後會誘發代謝路徑改變，產生類似於癌症細胞之瓦氏效應（Warburg effect），其特點有細胞大量攝取葡萄糖及乳糖累積細胞外。已知PI3K/Akt/mTOR訊息傳遞路徑能夠調控WSSV所誘發之瓦氏效應，但是否有其他宿主因子會影響此路徑，目前尚不清楚。Ras在人類癌症中為重要致癌基因，具有不同的異形體，其中又以K-Ras最為常見。本篇研究在白蝦中得到兩種K-Ras異構型，分別為RAS1及RAS2，並發現在基因體複製期（12 hpi）及晚期（24 hpi），RAS1/2之基因表現量及RAS之活性均有顯著提升。此外，RAS/ERK以及PI3K/Ak路徑於病毒感染後有活化現象。為了解Ras對於病毒複製之重要性，我們以Ras抑制劑Salirasib抑制Ras或以雙股RNA進行基因默化實驗。預處理Ras抑制劑造成WSSV基因體複製數及VP28基因表現量降低；而在分別處理RAS1/2雙股RNA後，VP28基因表現量皆有顯著降低，但WSSV基因體複製數僅有在靜默化RAS2的蝦隻中有顯著降低。總結本研究所得，RAS在基因體複製時期WSSV誘導之瓦氏效應及病毒複製中相當重要。

The White Spot Syndrome Virus (WSSV) has caused huge economic losses in the shrimp-farming industry all around the world. In previous studies, metabolic changes occurred in WSSV-infected shrimp resembling the Warburg effect (present in some cancer cells), namely increases in glucose consumption and plasma lactate concentrations at the replication stage (12 hpi). Although the Warburg effect can be regulated by a PI3K/Akt/mTOR pathway, how WSSV affects that pathway is unknown. Ras is a critical oncogene in human cancers, with K-Ras being the most common. We identified two types of K-Ras (designated RAS1 and RAS2) in L. vannamei and determined that gene expression of RAS1/2 was significantly increased after WSSV infection (12 and 24 hpi). Moreover, PI3K/Akt and RAS/ERK pathways were activated after WSSV infection. To determine importance of Ras in WSSV replication, studies were conducted to suppress Ras with Salirasib or silence Ras with dsRNA. Pre-treatment with inhibitor caused significant, dose-dependent decreases in WSSV genome copies. Moreover, after dsRNA treatment, at a late stage (24 hpi), there were decreases in gene expression of VP28, but viral genome copy number only decreased in RAS2-silenicng shrimp. We concluded that RAS was crucial in triggering WSSV-induced Warburg effect at the viral genome replication stage (12 hpi) and had an important role during WSSV replication.

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