虹彩病毒造成許多淡水或海水經濟魚種的系統性感染。其中之ㄧ為金目鱸虹彩病毒 (giant seaperch iridovirus ; GSIV)，分類上為虹彩病毒科 (Iridoviridae) 新區分出來的巨大細胞屬 (Megalocytivirus) 一員，與該屬的代表種之ㄧ嘉魶虹彩病毒 (red sea bream iridovirus ; RSIV) 在親源分析上序列非常接近。雖然有不少文獻指出虹彩病毒會導致宿主細胞進行細胞凋亡 (apoptosis)，但其中提到巨大細胞屬的病毒相關之研究卻很少，且虹彩病毒科病毒誘發細胞凋亡的機制亦尚未明瞭。在感染的石斑魚鰭細胞株 (GF-1) 細胞可以發現明顯細胞病變，並可觀察到下列現象：Annexin V-positive 或 PI-positive的細胞、粒線體膜電位喪失(mitochondrial membrane potential loss ; MMP loss)、mitochondria-mediated pathway 相關的 Bcl-2 family 蛋白 Bax 與 Bak 表現量增加，以及 caspase-3/7 與 caspase-9 活化。經由新合成蛋白抑制劑 CHX (Cycloheximide)、粒線體膜電位喪失抑制劑 BKA (Bongkrekic acid) 處理，皆可有效減緩上述情形的發生，並增加細胞存活率。穩定表現可抑制cytochrome c 釋放的Bcl-2 family 蛋白 zebra fish Bcl-xl 於石斑魚肝細胞株 (GL-av cells)，亦可抑制粒線體膜電位喪失，並增加存活率。綜合以上結果，GSIV 能透過 mitochondria-mediated pathway 誘發宿主細胞走向凋亡，而此過程需要新生蛋白的合成。此外，虹彩病毒科病毒誘使宿主細胞 Bcl-2 family 蛋白的表現量改變之現象目前為止尚未發表過，本實驗首次觀察到此現象。

A variety of freshwater and marine economical fish species are threatened by iridovirus-caused systemic diseases. One of them is giant seaperch iridovirus (GSIV), a red sea bream iridovirus (RSIV)-like Iridoviridae virus isolated from giant seaperch (Lates calcarifer). RSIV is a typical strain of Megalocytivirus, a new genus of Iridoviridae. Recently, some papers reported to inducing host cell apoptosis by iridovirus, but very few of them was induced by Megalocytivirus. Moreover, there is no evidence defining the molecular mechanism of this death pathway. GSIV infection induces the following features of apoptosis：(1) Annexin V-positive or PI-positive cells,(2) severe mitochondrial membrane potential (MMP) loss,(3) Bcl-2 family protein Bax and Bad upregulation and (4) caspase-3/7 and caspase-9 activation. Treatment with either protein newly synthesized inhibitor CHX (Cycloheximide) or treatment with MMP loss inhibitor BKA (Bongkrekic acid), could effectively block those events and enhanced the cellular viability. Anti-apoptotic Bcl-xl protein can prevent cytochrome c release and block MMP loss to enhance the cellular viability. Taken together, our results suggest that GSIV may induce mitochondria-mediated cell death via newly synthesized proteins-dependent pathway. Our study may provide new insight into iridovirus-induced molecular pathogenesis.

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