Comparison of the eIF-2α homologous proteins of seven ranaviruses (Iridoviridae)
Comparison of the eIF-2α homologous proteins of seven ranaviruses (Iridoviridae)
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DOI：
10.1023/a:1012533625571
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发表时间：
2001-01-01
期刊：
影响因子：
1.6
通讯作者：
Ahne, W
中科院分区：
文献类型：
--
作者：
Essbauer, S;Bremont, M;Ahne, W
真核起始因子2（eIF-2 α）的α亚基是细胞翻译机制的关键组分。在对细胞应激（如病毒感染）的反应中，eIF-2 α被双链RNA依赖性蛋白激酶（PKR）磷酸化，导致细胞蛋白质合成的抑制。eIF-2 α作为蛋白质合成的调节机制的重要性通过病毒用于下调PKR的各种策略来说明。因此，牛痘病毒编码K3 L蛋白，其类似于eIF-2 α并作为PKR的假底物抑制剂。流行性造血器官坏死病毒（EHNV）是虹彩病毒科蛙病毒属的成员，其基因组的核苷酸测序揭示了eIF-2 α等同基因。我们已经克隆并测序了几种鱼类和青蛙虹彩病毒的eIF-2 α基因。研究的虹彩病毒的eIF-2 α开放阅读框架和推导的蛋白质在核苷酸和氨基酸序列上都具有高度的同源性。在N-末端，虹彩病毒eIF-2 α显示出与各种物种的细胞起始因子2-α的N-末端、全长痘病毒eIF-2 α蛋白以及核糖体蛋白的S1结构域的显著同源性。比较相应的虹彩病毒蛋白与痘病毒和真核生物的eIF-2 α同源蛋白的氨基酸序列，揭示了基序的高度保守性。真核eIF-2 α和痘病毒和虹彩病毒eIF-2 α序列的系统发育分析已经证明了这些虹彩病毒的关系。为了研究eIF-2 α等同物的作用，在原核和真核（昆虫、鱼和鸡细胞）系统中表达了相应的基因。虹彩病毒eIF-2 α蛋白具有31 kDa的分子量，并且是细胞质的。虹彩病毒的细胞和病毒蛋白质合成可能受到与牛痘病毒类似的机制的调节。蛙病毒3，虹彩病毒科蛙病毒属的模式种，具有独特的翻译效率，而且，下调感染细胞的细胞蛋白质合成。
The alpha -subunit of the eukaryotic initiation factor 2 (eIF-2 alpha) is a key component of the translation machinery of the cell. In response to cellular stress such as viral infections, eIF-2 alpha is phosphorylated by double-stranded RNA-dependent protein kinase (PKR) leading to the inhibition of cellular protein synthesis. The importance of eIF-2 alpha as a regulatory mechanism for protein synthesis is illustrated by the wide variety of strategies employed by viruses to down-regulate PKR. Thus, Vaccinia virus encodes K3L protein, which resembles eIF-2 alpha and acts as a pseudo-substrate inhibitor of PKR. Nucleotide sequencing of the genome of epizootic haematopoietic necrosis virus (EHNV), a member of the genus ranavirus of Iridoviridae, has revealed an eIF-2 alpha equivalent gene. We have cloned and sequenced eIF-2 alpha genes of several iridoviruses of fishes and frogs. The eIF-2 alpha open reading frames and deduced proteins of the iridoviruses investigated exhibit a high degree of homology of both nucleotide and amino acid sequences. At the N-terminus, the iridoviral eIF-2 alpha shows significant homology to the N-termini of cellular initiation factor 2-alpha of various species, to full-length poxviral eIF-2 alpha proteins, and to the S1 domain of ribosomal proteins. Comparison of amino acid sequences of corresponding iridoviral proteins with eIF-2 alpha homologous proteins of poxviruses and eukaryotes has revealed a high conservation of motifs. A phylogenetic analysis of eukaryotic eIF-2 alpha and poxvirus and iridovirus eIF-2 alpha sequences has demonstrated the relationship of these iridoviruses. In order to investigate the role of the eIF-2 alpha equivalent, respective genes have been expressed in prokaryotic and eukaryotic (insect, fish and chicken cell) systems. The iridoviral eIF-2 alpha protein has a molecular weight of 31 kDa and is cytoplasmic. The cellular and viral protein synthesis of iridoviruses is probably regulated by a mechanism similar to that of Vaccinia virus. Frog-virus 3, the type species of the genus ranavirus of Iridoviridae, has a unique translational efficiency and, moreover, down-regulates the cellular protein synthesis of infected cells.