Modulation of iridovirus-induced apoptosis by endocytosis, early expression, JNK, and apical caspase.
Modulation of iridovirus-induced apoptosis by endocytosis, early expression, JNK, and apical caspase.
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DOI：
10.1016/j.virol.2007.09.010
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发表时间：
2008-01-20
期刊：
影响因子：
3.7
通讯作者：
Bilimoria SL
中科院分区：
文献类型：
--
作者：
Chitnis NS;D'Costa SM;Paul ER;Bilimoria SL
奇洛虹彩病毒（CIV）是虹彩病毒科的典型种，是一种大的、等长的细胞质dsDNA病毒。我们探讨了CIV诱导细胞凋亡的机制。高剂量CIV （CIVXS; 400 μg/ml）、紫外线照射病毒（CIVUV; 10 μg/ml）和CVPE （CIV蛋白提取物；10 μg/ml）诱导60%处理过的富菲拉毛线虫（ipr - cf - 124t）细胞凋亡。正常剂量的传染性CIV （10 μg/ml）仅诱导10%的富米假丝酵母（CF）细胞凋亡。细胞凋亡被顶端caspase抑制剂Z-IETD-FMK抑制，表明civ诱导的细胞凋亡需要caspase活性。CF细胞中推测的caspase被命名为CF -caspase-i。相对于模拟处理的细胞，CIVUV或CVPE在24小时内可使Cf-caspase-i活性提高80%。由于MAP激酶通路根据不同的环境诱导或抑制细胞凋亡，我们使用JNK抑制剂SP600125，并证明了对cvpe诱导的细胞凋亡的显著抑制。因此，JNK信号通路在该系统中对细胞凋亡具有重要意义。病毒与细胞表面的相互作用不足以导致细胞凋亡，因为与聚甾体微球结合的CIVUV颗粒不能诱导细胞凋亡。胞吞抑制剂（巴菲霉素或氯化铵）可否定CIVUV、CIVXS或CVPE诱导的细胞凋亡，表明需要通过该模式进入。鉴于对传染性CIV的弱凋亡反应，我们假设病毒基因表达抑制细胞凋亡。环己亚胺预处理的CIV感染细胞诱导69%的细胞凋亡，而正常感染的细胞凋亡率为10%。此外，用aphidicolin或磷酸阻断病毒DNA复制可抑制细胞凋亡和Cf-caspase-i活性，这表明早期病毒表达是抑制细胞凋亡的必要条件，而诱导不需要从头合成病毒蛋白。我们首次表明，在鸢尾病毒科的一种成员中，细胞凋亡：(i)需要病毒粒子或病毒粒子蛋白的进入和内吞作用，（ii）在允许早期病毒表达的条件下被抑制，（iii）需要JNK信号通路。这是昆虫病毒诱导细胞凋亡过程中JNK信号需求的首次报道。
Chilo iridescent virus (CIV) is the type species for the family Iridoviridae, which are large, isometric, cytoplasmic dsDNA viruses. We examined the mechanism of apoptosis induction by CIV. High CIV doses (CIVXS; 400 μg/ml), UV-irradiated virus (CIVUV; 10 μg/ml) and CVPE (CIV protein extract; 10 μg/ml) induced apoptosis in 60% of treated Choristoneura fumiferana (IPRI-CF-124T) cells. Normal doses of infectious CIV (10 μg/ml) induced apoptosis in only 10% of C. fumiferana (CF) cells. Apoptosis was inhibited by Z-IETD-FMK, an apical caspase inhibitor, indicating that CIV-induced apoptosis requires caspase activity. The putative caspase in CF cells was designated Cf-caspase-i. CIVUV or CVPE enhanced Cf-caspase-i activity by 80% at 24 h relative to mock-treated cells. Since the MAP kinase pathway induces or inhibits apoptosis depending on the context, we used JNK inhibitor SP600125 and demonstrated drastic suppression of CVPE-induced apoptosis. Thus, the JNK signaling pathway is significant for apoptosis in this system. Virus interaction with the cell surface was not sufficient for apoptosis since CIVUV particles bound to polysterene beads failed to induce apoptosis. Endocytosis inhibitors (bafilomycin or ammonium chloride) negated apoptosis induction by CIVUV, CIVXS or CVPE indicating that entry through this mode is required. Given the weak apoptotic response to infectious CIV, we postulated that viral gene expression inhibited apoptosis. CIV infection of cells pretreated with cycloheximide induced apoptosis in 69% of the cells compared to 10% in normal infections. Furthermore, blocking viral DNA replication with aphidicolin or phosphonoacetic acid suppressed apoptosis and Cf-caspase-i activity, indicating that early viral expression is necessary for inhibition of apoptosis, and de novo synthesis of viral proteins is not required for induction. We show for the first time that, in a member of the family Iridoviridae, apoptosis: (i) requires entry and endocytosis of virions or virion proteins, (ii) is inhibited under conditions permitting early viral expression, and (iii) requires the JNK signaling pathway. This is the first report of JNK signal requirement during apoptosis induction by an insect virus.
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影响因子：
3.7
作者：
IJkel, WFJ;Westenberg, M;Zuidema, D
通讯作者：
Zuidema, D
DOI：
10.1073/pnas.0438011100
发表时间：
2003-03-04
影响因子：
11.1
作者：
Lei, K;Davis, RJ
通讯作者：
Davis, RJ
影响因子：
3.7
作者：
Imajoh, M;Sugiura, H;Oshima, S
通讯作者：
Oshima, S
影响因子：
3.7
作者：
Carrascosa, AL;Bustos, MJ;Revilla, Y
通讯作者：
Revilla, Y
影响因子：
3.7
作者：
Chacon, MR;Almazan, F;Rodriguez, JF
通讯作者：
Rodriguez, JF