Lu Ling, Murphy Donald, Li Chunhua, Liu Shuanghu, Xia Xueshan, Pham Phiet Hoang, Jin Yuhuai, Hagedorn Curt H, Abe Kenji
Division of Gastroenterology-Hepatology and Nutrition, Department of Medicine, University of Utah, 30N 1900E, Salt Lake City, UT 84132, USA.
Institut National de Santé Publique du Québec, Laboratoire de Santé Publique du Québec, Sainte-Anne-de-Bellevue, QC, Canada.
J Gen Virol. 2008 Feb;89(Pt 2):444-452. doi: 10.1099/vir.0.83460-0.
In this study, the complete genomic sequence was determined for three hepatitis C virus variants (VT21, TV241 and TV249) of genotype 6 that do not classify within the established subtypes. All three genomes were isolated from patients in Vietnam and sequenced using 100 microl of serum. They showed 91.4-93.6% nucleotide similarities to each other but only 71.7-79.4% similarities to 17 reference sequences representing subtypes 6a-6q and to isolates km41 and gz52557. VT21, TV241 and TV249 displayed genome lengths of 9407, 9460 and 9445 nt, respectively. All three isolates contained a single open reading frame of 9051 nt while the 5'UTRs and 3'UTRs were 324-338 nt and 32-71 nt, respectively. They shared common sizes with QC227/6o and QC216/6p isolates in all ten protein regions. Phylogenetic analyses demonstrated that VT21, TV241 and TV249 clustered independently and were assigned subtype 6t, following the recent designations of 6r and 6s. Analysis of partial genomic sequences available for genotype 6 variants revealed five additional subtype 6t isolates, all originating from Vietnam. This analysis revealed two additional groups of isolates, and at least seven novel variants analogous to km41 and gz52557 that group independently and do not classify within the subtypes 6a-6t. This suggests the existence of at least 11 additional subtypes for genotype 6. In addition, the existence of isolates showing genetic distances greater than those within subtypes, but lesser than those between subtypes, raises interesting questions regarding the classification of HCV.
在本研究中，测定了6型丙型肝炎病毒的三种变异体（VT21、TV241和TV249）的完整基因组序列，这些变异体不属于已确定的亚型。所有三个基因组均从越南患者中分离得到，并使用100微升血清进行测序。它们彼此之间显示出91.4 - 93.6%的核苷酸相似性，但与代表6a - 6q亚型的17个参考序列以及分离株km41和gz52557的相似性仅为71.7 - 79.4%。VT21、TV241和TV249的基因组长度分别为9407、9460和9445个核苷酸。所有三个分离株都包含一个9051个核苷酸的单一开放阅读框，而5'非翻译区和3'非翻译区分别为324 - 338个核苷酸和32 - 71个核苷酸。它们在所有十个蛋白质区域与QC227/6o和QC216/6p分离株具有共同的大小。系统发育分析表明，VT21、TV241和TV249独立聚类，并按照最近对6r和6s的命名被指定为6t亚型。对6型变异体可用的部分基因组序列分析揭示了另外五个6t亚型分离株，均来自越南。该分析揭示了另外两组分离株，以及至少七个类似于km41和gz52557的新型变异体，它们独立聚类且不属于6a - 6t亚型。这表明6型至少还存在11个其他亚型。此外，存在一些分离株，其遗传距离大于亚型内的距离，但小于亚型间的距离，这引发了关于丙型肝炎病毒分类的有趣问题。
