目的:戊型肝炎病毒是世界范围内急性肝炎的主要病因,在免疫功能低下的个体中可进展为慢性。已经报道了在戊型肝炎病毒基因组的高变区中的各种病毒-宿主重组事件,但是组装和选择的模式仍然不清楚。
方法:为了进一步了解病毒进化,我们使用靶向下一代测序方法评估了16例急性或慢性感染患者样本中存在低丰度变异的情况.
结果:在七个样本中,鉴定了具有插入和/或缺失的不同变体。其中,来自人类基因或戊型肝炎病毒基因组的八个插入。可以鉴定五个不同的缺失。插入序列的氨基酸组成显示出较高的赖氨酸频率和较低的脯氨酸丰度,此外,乙酰化和泛素化位点的频率高于戊型肝炎病毒野生型序列.
结论:这些发现表明,插入的核苷酸组成和翻译后修饰位点可能有助于重组事件。尽管低水平戊型肝炎病毒变异的影响尚不确定,我们的结果强调了高度敏感的下一代测序方法对于捕获高变区的全部多样性的重要性.
Hepatitis E virus is a major cause of acute hepatitis worldwide and can progress to chronicity in immunocompromised individuals. Various virus-host recombination events have been reported in the hypervariable region of the hepatitis E virus genome, but the patterns of assembly and selection remain unclear.
To gain further insight into viral evolution, we assessed the presence of low abundance variants in 16 samples from individuals with acute or chronic infection using a targeted next-generation sequencing approach.
In seven samples, different variants with insertions and/or deletions were identified. Among them, eight insertions originating either from human genes or from the hepatitis E virus genome. Five different deletions could be identified. The amino acid composition of sequences with insertions showed a higher frequency of lysine and a lower abundance of proline, and additionally acetylation and ubiquitination sites were more frequent than in hepatitis E virus wild-type sequences.
These findings suggest that the nucleotide composition of insertions and sites for post-translational modification may contribute to recombination events. Although the impact of low-level hepatitis E virus variants is uncertain, our results highlight the importance of a highly sensitive next-generation sequencing approach to capture the full diversity of hypervariable region.