Characterization of a recombinant type 3 type 2 poliovirus isolated from a healthy vaccinee and containing a chimeric capsid protein VP1

Characterization of a recombinant type 3 type 2 poliovirus isolated from a healthy vaccinee and containing a chimeric capsid protein VP1
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DOI:
10.1099/vir.0.18708-0
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发表时间:
2003-03-01
影响因子:
3.8
通讯作者:
Hovi, T
Hovi, T
中科院分区:
医学3区
文献类型:
--
作者:
Blomqvist, S;Bruu, AL;Hovi, T

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在口服脊髓灰质炎病毒疫苗接种约12周后,从一名2岁健康男童的粪便标本中分离到一株Sabin 3/Sabin 2/Sabin 3(S3/2/3)型重组脊髓灰质炎病毒。第一个重组连接位于编码VP1衣壳蛋白的基因组区域,位于核苷酸位置3274和3285之间(编号根据Sabin 3),第二个重组连接位于RNA聚合酶区域(核苷酸位置6824和6825)。该重组将6个Sabin 2衍生的氨基酸引入到VP1羧基末端的Sabin 3衣壳环境中。重组病毒的全基因组在33个核苷酸位置上与相应的亲本Sabin毒株不同,其中9个核苷酸位置导致氨基酸替换。衣壳蛋白中有4个替换,非结构蛋白编码区有5个替换。抗原位2B有1个氨基酸发生改变,3B位有2个氨基酸发生改变。此外,S3/2/3株的整个抗原点3A被Sabin 2特异性氨基酸取代,但S3/2/3株的抗原性没有表现出2型特异性。用灭活脊髓灰质炎病毒疫苗免疫的芬兰儿童血清中的中和抗体效价并不低于对重组病毒的中和抗体滴度。我们的结果表明,嵌合病毒最有可能是由疫苗接种者体内的重组事件产生的,而不是代表正在传播的疫苗衍生病毒的后代。
A Sabin 3/Sabin 2/Sabin 3 (S3/2/3) intertypic recombinant poliovirus was isolated from a faecal specimen from a 2-year-old healthy boy approximately 12 weeks after administration of oral poliovirus vaccine. The first recombination junction was in the genomic region encoding the VP1 capsid protein between nucleotide positions 3274 and 3285 (numbering according to Sabin 3) and the second was in the RNA polymerase region (nucleotide positions 6824 and 6825). The recombination had introduced six Sabin 2-derived amino acids into the Sabin 3 capsid environment in the carboxyl terminus of VP1. The complete genome of the recombinant virus differed from corresponding parental Sabin strains at 33 nucleotide positions, nine of them resulting in an amino acid substitution. Four substitutions were in the capsid proteins and five were in the region encoding the non-structural proteins. One amino acid was changed in the antigenic site 2B and two in site 3B. In addition, the whole antigenic site 3A was replaced by Sabin 2-specific amino acids, but the antigenic characteristics of the S3/2/3 did not show type 2-specific features. Neutralizing antibody titres in sera from Finnish children immunized with the inactivated poliovirus vaccine were not lower against the recombinant virus than against Sabin 3. Our results suggest that the chimeric virus was most likely generated by recombination events in the vaccinee, rather than representing progeny of circulating vaccine-derived virus.