Simmonds P, Smith D B, McOmish F, Yap P L, Kolberg J, Urdea M S, Holmes E C
Department of Medical Microbiology, University of Edinburgh, U.K.
J Gen Virol. 1994 May;75 ( Pt 5):1053-61. doi: 10.1099/0022-1317-75-5-1053.
Isolates of hepatitis C virus (HCV) show considerable nucleotide sequence variability throughout the genome. Comparisons of complete genome sequences have been used as the basis of classification of HCV into a number of genotypes that show 67 to 77% sequence similarity. In order to investigate whether sequence relationships between genotypes are equivalent in different regions of the genome, we have carried out formal sequence analysis of variants in the 5' non-coding region (5'NCR) and in the genes encoding the core protein, an envelope protein (E1) and a non-structural protein (NS-5). In the E1 region, variants grouped into a series of six major genotypes and a series of subtypes that could be matched to the phylogenetic groupings previously observed for the NS-5 region. Furthermore, core and E1 sequences showed three non-overlapping ranges of sequence similarity corresponding to those between different genotypes, subtypes and isolates previously described in NS-5. Each major genotype could also be reliably identified by sequence comparisons in the well conserved 5'NCR, although many subtypes, such as 1a/1b, 2a/2c and some of those of type 4, could not be reliably distinguished from each other in this region. These data indicate that subgenomic regions such as E1 and NS-5 contain sufficient phylogenetic information for the identification of each of the 11 or 12 known types and subtypes of HCV. No evidence was found for variants of HCV that had sequences of one genotype in the 5'NCR but of a different one in the E1 or NS-5 region. This suggests that recombination between different HCV types is rare or non-existent and does not currently pose a problem in the use of subgenomic regions in classification.
丙型肝炎病毒（HCV）分离株在整个基因组中表现出相当大的核苷酸序列变异性。完整基因组序列的比较已被用作将HCV分类为多种基因型的基础，这些基因型显示出67%至77%的序列相似性。为了研究不同基因组区域中基因型之间的序列关系是否等同，我们对5'非编码区（5'NCR）以及编码核心蛋白、包膜蛋白（E1）和非结构蛋白（NS-5）的基因中的变异体进行了正式的序列分析。在E1区域，变异体分为六个主要基因型系列和一系列亚型，这些亚型可以与先前在NS-5区域观察到的系统发育分组相匹配。此外，核心序列和E1序列显示出三个不重叠的序列相似性范围，与先前在NS-5中描述的不同基因型、亚型和分离株之间的相似性范围相对应。每个主要基因型也可以通过在高度保守的5'NCR中的序列比较可靠地鉴定出来，尽管许多亚型，如1a/1b、2a/2c以及4型中的一些亚型，在该区域无法可靠地区分彼此。这些数据表明，诸如E1和NS-5等亚基因组区域包含足够的系统发育信息，可用于鉴定已知的11种或12种HCV类型和亚型中的每一种。未发现HCV变异体在5'NCR中具有一种基因型的序列，但在E1或NS-5区域中具有不同基因型序列的证据。这表明不同HCV类型之间的重组很少见或不存在，目前在亚基因组区域用于分类时不会造成问题。
