RNA SEQUENCE VARIANTS IN LIVE POLIOVIRUS VACCINE AND THEIR RELATION TO NEUROVIRULENCE

RNA SEQUENCE VARIANTS IN LIVE POLIOVIRUS VACCINE AND THEIR RELATION TO NEUROVIRULENCE
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DOI:
10.1128/jvi.66.2.966-970.1992
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发表时间:
1992-02-01
影响因子:
5.4
通讯作者:
LEVENBOOK, IS
LEVENBOOK, IS
中科院分区:
医学2区
文献类型:
--
作者:
CHUMAKOV, KM;NORWOOD, LP;LEVENBOOK, IS

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利用聚合酶链反应和限制性内切酶裂解(MAPREC)突变体分析,研究了3型脊髓灰质炎减毒病毒与野生型祖病毒不同位点的序列异质性和稳定性。在测试的七个基因组位置中,只有两个(位置472和2493)显示核苷酸异质性。疫苗病毒在细胞培养物中的繁殖导致在基因组的这两个位置具有逆转的病毒的快速选择。472位点突变的相对丰度与猴子神经毒力测试结果相关,而2493位点突变与病毒在猴子中的神经毒力不直接相关。相反,后一个位置的突变丰度与种子病毒的来源及其传代水平有关。这些结果进一步表明,472位点的MAPREC可用于评价3型脊髓灰质炎病毒疫苗的质量。
Mutant analysis by polymerase chain reaction and restriction enzyme cleavage (MAPREC) was used to study sequence heterogeneity and stability in attenuated poliovirus type 3 at positions in which the vaccine virus differs from its wild-type progenitor. Of seven genomic positions tested, only two (positions 472 and 2493) show nucleotide heterogeneity. Propagation of the vaccine virus in cell cultures leads to rapid selection of virus with reversions at these two positions of the genome. The relative abundance of reversions at position 472 correlates with the result of monkey neurovirulence tests, while the mutation at position 2493 is not directly associated with neurovirulence of the virus in monkeys. Instead, the abundance of mutations at the latter position correlates with the source of the seed virus and its passage level. These results further indicate that MAPREC at position 472 can be used to assess the quality of poliovirus type 3 vaccine.