Functional analysis of the inhibitor of apoptosis (iap) gene carried by the entomopoxvirus of Amsacta moorei.
Functional analysis of the inhibitor of apoptosis (iap) gene carried by the entomopoxvirus of Amsacta moorei.
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莫雷昆虫痘病毒携带的凋亡抑制剂（iap）基因的功能分析。
DOI：
10.1128/jvi.79.4.2335-2345.2005
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发表时间：
2005
影响因子：
5.4
通讯作者：
Moyer,RichardW
中科院分区：
文献类型：
--
作者：
Li,Qianjun;Liston,Peter;Moyer,RichardW
来自木蠹蛾（Amsacta moorei，AmEPV）的昆虫痘病毒（entomopoxvirus）不含脊椎动物痘病毒凋亡抑制基因。然而，AmEPV携带一个单一的细胞凋亡抑制因子（iap）基因（AMViap），在脊椎动物痘病毒中不存在。AMViap基因与果蝇抑凋亡基因在Ld 652细胞中共表达时具有活性，并且可以拯救细胞免于凋亡，如存活细胞数量增加和caspase-3样活性水平降低所示。我们还发现AMViapgene的表达挽救了苜蓿银纹夜蛾核型多角体病毒（AcMNPV）Δp35感染的Sf 9细胞在凋亡诱导的其他失败感染期间的多面体生产。令人惊讶的是，从AmEPV基因组中删除AMViapgene仅导致感染的Ld 652细胞中病毒体产生的适度（10倍）损失，表明AMViapgene对于这些条件下的病毒复制是不必要的。然而，Ld 652细胞感染AmEPV缺乏一个functionaliapgene导致更快的诱导细胞毒性和caspase-3样活性的水平增加。观察到类似的结果，并且在感染的Sf 9和S2细胞中更明显。纯化的AMVIAP蛋白还在体外抑制人caspase-9和caspase-3的酶活性。我们的研究结果表明，虽然AMViapgene通过内在途径在控制细胞凋亡中是活跃的，但病毒可能编码另外的蛋白质，这些蛋白质也调节细胞凋亡。
The entomopoxvirus fromAmsacta moorei(AmEPV) contains none of the commonly recognized vertebrate poxvirus apoptotic suppressor genes. However, AmEPV carries a single inhibitor of apoptosis (iap) gene (AMViap) not present in vertebrate poxviruses. The AMViapgene was active when coexpressed with theDrosophilaproapoptotic genehidin Ld652 cells and can rescue cells from apoptosis as shown by increased number of surviving cells and reduced levels of caspase-3-like activity. We also showed that expression of the AMViapgene rescued polyhedron production inAutographa californica Mnucleopolyhedrovirus (AcMNPV)Δp35-infected Sf9 cells during an otherwise abortive infection induced by apoptosis. Surprisingly, deletion of the AMViapgene from the AmEPV genome led to only a modest (10-fold) loss of virion production in infected Ld652 cells, indicating that the AMViapgene is nonessential for virus replication under these conditions. However, infection of Ld652 cells by AmEPV lacking a functionaliapgene led to a more rapid induction of cytotoxicity and increased levels of caspase-3-like activity. Similar results were observed and were more pronounced in infected Sf9 and S2 cells. The purified AMVIAP protein also inhibits the enzymatic activities of human caspase-9 and caspase-3 in vitro. Our results indicate that while the AMViapgene was active in controlling apoptosis through the intrinsic pathway, the virus likely encodes additional proteins that also regulate apoptosis.