Biological significance of the U residue at the -3 position of the mRNA sequences of influenza A viral segments PB1 and NA
Biological significance of the U residue at the -3 position of the mRNA sequences of influenza A viral segments PB1 and NA
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DOI：
10.1016/j.virusres.2003.11.013
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发表时间：
2004-03-15
期刊：
影响因子：
5
通讯作者：
Kawaoka, Y
中科院分区：
文献类型：
--
作者：
Maeda, Y;Goto, H;Kawaoka, Y
受感染细胞中的病毒蛋白水平被认为受到多种机制的调节。 A/WSN/33 (H1N1) 流感病毒的 PB1 和 NA 蛋白的起始密码子位于翻译欠佳的 Kozak 序列中。为了确定这些次优 Kozak 序列的重要性，构建了模型 vRNA，其编码区被报告基因 SEAP 基因（分泌型碱性磷酸酶）替换，并构建了具有 PB1 和 NA 最佳 Kozak 序列的重组病毒。 PB 1 和 NA 起始密码子上游序列向最佳 Kozak 序列的转换反映在报告蛋白表达水平上，但不反映在 PB1 和 NA 蛋白表达水平上。具有 PB1、NA 或这两个基因的最佳 Kozak 序列的重组病毒在细胞培养物和小鼠体内都具有与野生型病毒相似的复制特性。这些结果表明，PB1 和 NA 蛋白的表达受控制这些蛋白翻译起始的机制以外的机制调节。 (C) 2003 Elsevier B.V. 保留所有权利。
The levels of viral proteins in infected cells are thought to be regulated by a variety of mechanisms. The initiation codons for the PB1 and NA proteins of A/WSN/33 (H1N1) influenza virus are in a suboptimal Kozak sequence for translation. To determine the significance of these suboptimal Kozak sequences, model vRNAs, whose coding regions were replaced with the reporter SEAP gene (for secreted alkaline phosphatase) and recombinant viruses with optimal Kozak sequences for PB1 and NA were constructed. Conversion of the upstream sequence of the PB 1 and NA initiation codon to an optimal Kozak sequence was reflected in the level of reporter protein expression, but not the level of PB1 and NA protein expression. The recombinant viruses that had optimal Kozak sequences for PB1, NA, or both genes had similar replicative properties, both in cell culture and in mice, to those of the wild-type virus. These results suggest that expression of the PB1 and NA proteins is regulated by a mechanism other than that controlling the initiation of translation of these proteins. (C) 2003 Elsevier B.V. All rights reserved.