Elsevier

Virology

Volume 485, November 2015, Pages 460-466
Virology

Detection of hypermutated human papillomavirus type 16 genome by Next-Generation Sequencing

https://doi.org/10.1016/j.virol.2015.08.017Get rights and content
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Abstract

Human papillomavirus type 16 (HPV16) is a major cause of cervical cancer. We previously demonstrated that C-to-T and G-to-A hypermutations accumulated in the HPV16 genome by APOBEC3 expression in vitro. To investigate in vivo characteristics of hypermutation, differential DNA denaturation-PCR (3D-PCR) was performed using three clinical specimens obtained from HPV16-positive cervical dysplasia, and detected hypermutation from two out of three specimens. One sample accumulating hypermutations in both E2 and the long control region (LCR) was further subjected to Next-Generation Sequencing, revealing that hypermutations spread across the LCR and all early genes. Notably, hypermutation was more frequently observed in the LCR, which contains a viral replication origin and the early promoter. APOBEC3 expressed abundantly in an HPV16-positive cervix, suggesting that single-stranded DNA exposed during viral replication and transcription may be efficient targets for deamination. The results further strengthen a role of APOBEC3 in introducing HPV16 hypermutation in vivo.

Keywords

HPV16
Hypermutation
APOBEC3
Cervical cancer
Next-Generation Sequencing

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These authors contributed equally to this study.