Full-length open reading frame of a recombinant hepatitis C virus strain from St Petersburg: proposed mechanism for its formation
Full-length open reading frame of a recombinant hepatitis C virus strain from St Petersburg: proposed mechanism for its formation
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DOI：
10.1099/vir.0.79984-0
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发表时间：
2004-07-01
影响因子：
3.8
通讯作者：
Magnius, LO
中科院分区：
文献类型：
--
作者：
Kalinina, O;Norder, H;Magnius, LO
对丙型肝炎病毒重组株RF12k/1b(N687)和非重组1b株N589的全长ORFs进行了测序。C、E1、E2、p7、NS2、NS3、NS4和NS5基因的大小与亲本亚型一致。NS5A蛋白的PKR-eIF2α磷酸化位点同源区域序列与2型株相同，而NS5A蛋白的干扰素-α敏感性决定区与干扰素耐药株相同。对于亲本菌株，预测了两个发夹结构，HS1和HS2，在交叉位点的正链上下游，这在重组菌株中不存在。HS2与萝卜皱缩病毒RNA的基序1发夹相似，该基序与依赖RNA的RNA聚合酶结合，并在重组过程中促进3‘端的延伸。这项研究表明，由于3‘-亲本基因组HS1发夹的限制，在负链合成过程中，由于3’-亲本基因组HS1发夹的限制，RF1_2k/1b通过同源重组出现。
The full-length ORFs for the hepatitis C virus recombinant RF1_2k/1b (N687) and the non-recombinant 1b strain N589 were sequenced. A single recombination point was found and the sizes of the genes (C, E1, E2, p7, NS2, NS3, NS4 and NS5) were according to the parental subtypes. The PKR-eIF2alpha phosphorylation site homology domain sequence of the E2 protein was identical to those of genotype 2 strains, while the IFN-alpha-sensitivity-determining region of the NS5A protein was identical to those of interferon-resistant 1b strains. For the parental strains, two hairpin structures, HS1 and HS2, were predicted for the plus-strand up- and downstream of the crossover site, which were not present in the recombinant strain. HS2 shared similarity with the motif 1 hairpin of turnip crinkle virus RNA that binds to the RNA-dependent RNA polymerase and facilitates 3'-terminal extension during recombination. This study suggests that RF1_2k/1b has emerged by homologous recombination during minus-strand synthesis via template switching because of constraints imposed by the HS1 hairpin of the 3'-parental genome.