MOLECULAR AND BIOLOGICAL CHANGES IN THE COLD-ADAPTED MASTER STRAIN-A/AA/6/60(H2N2) INFLUENZA-VIRUS
MOLECULAR AND BIOLOGICAL CHANGES IN THE COLD-ADAPTED MASTER STRAIN-A/AA/6/60(H2N2) INFLUENZA-VIRUS
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DOI：
10.1073/pnas.90.13.6032
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发表时间：
1993-07-01
影响因子：
11.1
通讯作者：
WEBSTER, RG
中科院分区：
文献类型：
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作者：
HERLOCHER, ML;MAASSAB, HF;WEBSTER, RG
冷适应(Ca)A/AA/6/60流感活疫苗正在进行商业开发，供世界各地的儿童使用，并被用作其他活疫苗的模型。尽管它已被证明是安全的和免疫原性的，但冷适应的分子基础从未被确定。为了确定导致冷适应的序列变化，我们将CA疫苗主毒株的序列与其前体野生型病毒wtA/AA/6/60E2(Wt2)进行了比较。在3个基因片段中，只有4个碱基差异编码2个氨基酸差异。计算机预测的RNA折叠在ca和wt2分子之间投射出不同的二级结构，这是基于它们之间的两个沉默的差异。编码酸性聚合酶、基质和非结构蛋白的基因在两种病毒中是相同的。CAA/AA/6/60病毒在原代鸡肾细胞中经过25℃的长时间逐步传代后发现的几个差异表明，冷适应导致高度可变的RNA基因组具有更大的遗传稳定性。
The live cold-adapted (ca) A/AA/6/60 influenza vaccine is being commercially developed for worldwide use in children and is being used as a model for other live vaccines. Although it has been proven safe and immunogenic, the molecular basis of cold adaptation has never been determined. To identify sequence changes responsible for cold adaptation, we have compared the sequence of the master ca vaccine strain to its progenitor wild-type virus, wt A/AA/6/60 E2 (wt2). Only 4 nt differences encoding 2 aa differences were found in three gene segments. Computer-predicted RNA folds project different secondary structures between the ca and wt2 molecules based on the two silent differences between them. Genes coding for the acidic polymerase, matrix, and nonstructural proteins are identical between the two viruses. The few differences found in the ca A/AA/6/60 virus after its long stepwise passage at 25-degrees-C in primary chicken kidney cells suggest that cold adaptation resulted in greater genetic stability for the highly variable RNA genome.