高危人乳头瘤病毒 (HPV) 感染是导致宫颈癌的原因。然而，人们对 HPV 类型和风险类别之间关于其遗传多样性的差异知之甚少，特别是 APOBEC3 诱导的突变（这些突变有助于对 HPV 的先天免疫反应）。使用基于捕获的下一代测序，从 2017 年采样的 30 名多哥女性性工作者 (FSW) 的配对宫颈和肛门拭子中生成了涵盖 43 种 HPV 类型的 156 个 HPV 全基因组序列。遗传多样性和 APOBEC3 诱导的突变在病毒全基因组和基因水平。涵盖宫颈和肛门拭子中 24 种 HPV 类型的 34 对序列比较显示，两个解剖部位存在相同的感染。观察到患者之间 HPV 类型的遗传多样性存在差异。与高危 HPV (hrHPV) 相比，E6 基因在低危 HPV (lrHPV) 中的保守性显着较低 (p = 0.009)。发现 APOBEC3 诱导的突变在 lrHPV 中比在 hrHPV 中更常见 (p = 0.005)，这得到了我们的数据和 GenBank 数据库中大型 HPV 序列集的支持。关注最常见的 lrHPV 6 和 11 以及 hrHPV 16 和 18，APOBEC3 诱导的突变主要发现于 lrHPV 的 E4 和 E6 基因中，但在 hrHPV 的这些基因中几乎不存在。可变的 APOBEC3 突变特征可能导致 HPV 之间不同的致癌潜力。需要进一步研究来最终确定 APOBEC3 编辑水平是否与 HPV 在类型和亚谱系尺度上的致癌潜力相关。© 2024 作者。 《医学病毒学杂志》由 Wiley periodicals LLC 出版。

High-risk human papillomavirus (HPV) infections are responsible for cervical cancer. However, little is known about the differences between HPV types and risk categories regarding their genetic diversity and particularly APOBEC3-induced mutations - which contribute to the innate immune response to HPV. Using a capture-based next-generation sequencing, 156 HPV whole genome sequences covering 43 HPV types were generated from paired cervical and anal swabs of 30 Togolese female sex workers (FSWs) sampled in 2017. Genetic diversity and APOBEC3-induced mutations were assessed at the viral whole genome and gene levels. Thirty-four pairwise sequence comparisons covering 24 HPV types in cervical and anal swabs revealed identical infections in the two anatomical sites. Differences in genetic diversity among HPV types was observed between patients. The E6 gene was significantly less conserved in low-risk HPVs (lrHPVs) compared to high-risk HPVs (hrHPVs) (p = 0.009). APOBEC3-induced mutations were found to be more common in lrHPVs than in hrHPVs (p = 0.005), supported by our data and by using large HPV sequence collections from the GenBank database. Focusing on the most common lrHPVs 6 and 11 and hrHPVs 16 and 18, APOBEC3-induced mutations were predominantly found in the E4 and E6 genes in lrHPVs, but were almost absent in these genes in hrHPVs. The variable APOBEC3 mutational signatures could contribute to the different oncogenic potentials between HPVs. Further studies are needed to conclusively determine whether APOBEC3 editing levels are associated to the carcinogenic potential of HPVs at the type and sublineage scales.© 2024 The Author(s). Journal of Medical Virology published by Wiley Periodicals LLC.