Klinikum der Johann Wolfgang Goethe-Universität, Medizinische Klinik 1, Frankfurt am Main, Germany.
J Viral Hepat. 2011 Mar;18(3):181-92. doi: 10.1111/j.1365-2893.2010.01296.x.
The aim of the present study was to investigate the variability of hepatitis C virus (HCV) CD81 binding regions (CD81-1/2) in peripheral blood mononuclear cells (PBMC)-derived and serum-derived HCV-RNA samples. HCV-RNA was isolated from PBMC (10⁴ cells) and serum samples from 37 patients chronically infected with HCV genotype 1a/1b (n=21/16). The hypervariable regions 1/2 (amino acid 384-410, amino acid 474-482) and regions CD81-1/2 (amino acid 474-494, amino acid 522-551) were analysed. Mutational frequency of amino acid sequences was compared between PBMC-derived and serum-derived HCV variants as well as local accumulation of mutations. Furthermore, CD81 was quantified on PBMC. Mutational frequency was not different between PBMC-derived and serum-derived HCV variants. A trend to lower mutational frequency in genotype 1a PBMC variants compared with serum-derived variants was observed in region CD81-2 (5%vs 10%). Smoothed mutational frequency analysis showed a significantly lower variability within genotype 1a CD81-2 in PBMC-derived compared to serum-derived HCV-RNA (P=0.026). CD81 expression on PBMC was not correlated with the number of mutations within the CD81 binding regions.
A higher conservation was observed in region CD81-2 in PBMC-derived versus serum-derived HCV-RNA indicating selection of HCV variants on PBMC. The variability in the CD81 binding regions appeared to be independent from CD81 expression.
本研究旨在探讨丙型肝炎病毒（HCV）CD81 结合区域（CD81-1/2）在外周血单个核细胞（PBMC）衍生和血清衍生 HCV-RNA 样本中的变异性。从慢性 HCV 基因型 1a/1b 感染患者（n=21/16）的 PBMC（10⁴个细胞）和血清样本中分离 HCV-RNA。分析了高度可变区 1/2（氨基酸 384-410、氨基酸 474-482）和 CD81-1/2 区（氨基酸 474-494、氨基酸 522-551）。比较了 PBMC 衍生和血清衍生 HCV 变异体中氨基酸序列的突变频率以及突变的局部聚集。此外，还对 PBMC 上的 CD81 进行了定量。PBMC 衍生和血清衍生 HCV 变异体之间的突变频率没有差异。在 CD81-2 区观察到基因型 1a PBMC 变异体的突变频率较血清衍生变异体降低的趋势（5%比 10%）。平滑突变频率分析显示，基因型 1a CD81-2 中 PBMC 衍生 HCV-RNA 的变异性明显低于血清衍生 HCV-RNA（P=0.026）。CD81 在 PBMC 上的表达与 CD81 结合区的突变数量无关。
在 PBMC 衍生的 HCV-RNA 中，CD81-2 区的保守性更高，表明 HCV 变异体在 PBMC 上受到选择。CD81 结合区的变异性似乎与 CD81 表达无关。
