Centre for Forensic Science, University of Western Australia, Western Australia, Australia.
Hepatology. 2011 Feb;53(2):396-405. doi: 10.1002/hep.24076. Epub 2011 Jan 18.
The host's immune response to hepatitis C virus (HCV) can result in the selection of characteristic mutations (adaptations) that enable the virus to escape this response. The ability of the virus to mutate at these sites is dependent on the incoming virus, the fitness cost incurred by the mutation, and the benefit to the virus in escaping the response. Studies examining viral adaptation in chronic HCV infection have shown that these characteristic immune escape mutations can be observed at the population level as human leukocyte antigen (HLA)-specific viral polymorphisms. We examined 63 individuals with chronic HCV infection who were infected from a single HCV genotype 1b source. Our aim was to determine the extent to which the host's immune pressure affects HCV diversity and the ways in which the sequence of the incoming virus, including preexisting escape mutations, can influence subsequent mutations in recipients and infection outcomes.
HCV sequences from these individuals revealed 29 significant associations between specific HLA types within the new hosts and variations within their viruses, which likely represent new viral adaptations. These associations did not overlap with previously reported adaptations for genotypes 1a and 3a and possibly reflected a combination of constraint due to the incoming virus and genetic distance between the strains. However, these sites accounted for only a portion of the sites in which viral diversity was observed in the new hosts. Furthermore, preexisting viral adaptations in the incoming (source) virus likely influenced the outcomes in the new hosts.
宿主对丙型肝炎病毒（HCV）的免疫反应可导致病毒选择出特征性突变（适应性），使病毒能够逃避这种反应。病毒在这些部位发生突变的能力取决于进入的病毒、突变带来的适应性成本，以及病毒逃避反应的益处。研究慢性 HCV 感染中的病毒适应性表明，这些特征性免疫逃逸突变可以在人群水平上作为人类白细胞抗原（HLA）特异性病毒多态性观察到。我们检查了 63 名来自单一 HCV 基因 1b 来源的慢性 HCV 感染者。我们的目的是确定宿主免疫压力对 HCV 多样性的影响程度，以及进入病毒的序列（包括预先存在的逃逸突变）如何影响受者的后续突变和感染结果。
这些个体的 HCV 序列揭示了新宿主内特定 HLA 类型与病毒内变异之间的 29 个显著关联，这可能代表新的病毒适应性。这些关联与先前报道的基因型 1a 和 3a 的适应性没有重叠，可能反映了由于进入的病毒和菌株之间的遗传距离而导致的约束的组合。然而，这些位点仅占新宿主中观察到病毒多样性的部分位点。此外，进入（来源）病毒中的预先存在的病毒适应性可能影响新宿主的结局。
