FRAME SHIFT MUTATIONS AS A NOVEL MECHANISM FOR THE GENERATION OF NEUTRALIZATION RESISTANT MUTANTS OF HUMAN RESPIRATORY SYNCYTIAL VIRUS

FRAME SHIFT MUTATIONS AS A NOVEL MECHANISM FOR THE GENERATION OF NEUTRALIZATION RESISTANT MUTANTS OF HUMAN RESPIRATORY SYNCYTIAL VIRUS
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DOI:
10.1002/j.1460-2075.1990.tb07642.x
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发表时间:
1990-12-01
期刊:
影响因子:
11.4
通讯作者:
MELERO, JA
MELERO, JA
中科院分区:
生物学1区
文献类型:
--
作者:
GARCIABARRENO, B;PORTELA, A;MELERO, JA

文献摘要

被引文献

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报道了4株人类呼吸道合胞病毒(RS)病毒突变株对63g单抗的抗药性。G蛋白基因的序列来自:(I)mRNA来源的重组体,(Ii)mRNA直接测序和(Iii)扩增的vRNA来源的cDNA。结果表明,从单个斑块中恢复的原始逃逸突变体含有不同的病毒种群。这种异质性影响了G蛋白基因588或623核苷酸之后存在的腺苷残基的数量。在第二个空斑纯化步骤后恢复的突变病毒产生了同质序列,但与长序列相比,这两个位置含有单一的腺苷插入或缺失。这些基因改变导致了移码改变,这反映在突变G蛋白的抗原性和结构属性上。讨论了RS病毒G蛋白基因移码突变的起源和重要性。
The genetic characterization of four previously reported mutants of human respiratory syncytial (RS) virus resistant to monoclonal antibody 63G is described. Sequences of the G protein genes were obtained from: (i) mRNA derived cDNA recombinants, (ii) direct mRNA sequencing and (iii) amplified vRNA derived cDNAs. The results obtained indicate that the original escape mutants, recovered from individual plaques, contained heterogeneous viral populations. This heterogeneity affected the number of adenosine residues present after nucleotides 588 or 623 of the G protein gene. Mutant viruses recovered after a second plaque purification step generated homogeneous sequences but contained single adenosine insertions or deletions at those two sites compared with the Long sequence. These genetic alterations introduced frameshift changes which are reflected in both the antigenic and structural properties of the mutant G proteins. The origin and importance of frameshift mutations in the RS virus G protein gene are discussed.