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. 2024 Apr 16;15(5):e00729-24. doi: 10.1128/mbio.00729-24

Fig 2.

Tables list the locations where HPV DNA and RNA have integrated into the host genome with sequencing data maps. Illustrations locate HPV16 integration site on chromosome 4 with four isoforms and HPV18 on chromosome 8 with three isoforms.

RNA transcription, splicing, and polyadenylation from a single HPV DNA integration site in the HPV16 cervical cancer tissue A1BJ and HPV18 cervical cancer tissue A3HE. (A and E) Distributions of the DNA CJRs mapped to the chimeric HPV16- or HPV18-host chromosomes in the frequency order of the determined unique junction reads in the tissues A1BJ (A) and A3HE (E). (B and F) The mapped RNA CJRs (≥2 CJRs) from RNA-seq of the tissues A1BJ (B) and A3HE (F) to the chimeric virus-host genome. (C and G) Mapping and visualization of HPV-specific reads from DNA-seq and RNA-seq to the HPV16-hg38 genome (C) and to the HPV18-hg38 genome (G) by IGV. (D) The mapped HPV16 DNA integration site in the intergenic region between CXCL6 and RASSF6 genes on Chr4 in the tissue A1BJ. Expression of viral E6E7 RNA from the integrated DNA is shown as a chimeric virus-host RNA, with RNA-seq reads-coverage (0–6,000 scale) and Sashimi plots for splice directions illustrated by IGV (middle). Numbers above or below the diagrams indicate the virus (yellow) or host (blue) genome nucleotide (nt) positions, the viral early promoter P97 (arrows), the host polyadenylation signal (PAS), and the RNA splice sites. Four isoforms of HPV16-host fusion RNA identified were transcribed from the viral early promoter and polyadenylated by using a host PAS at Chr4 nt 73,777,512. This integration of HPV16 DNA led to ~4.5 kb loss of the viral genome region from nt 1,937 to nt 6,514. URR, upstream regulatory region; 7906/1, viral genome tail-to-head junction. The number below each isoform RNA indicates the estimated length of the RNA without a pA tail. (H) Diagram showing the mapped HPV18 DNA in the intron 6 region of PVT1 (GENCODE V44) on Chr8 in the tissue A3HE and the expression of the virus-host fusion RNA from the viral early promoter P55/102. A host PAS at Chr8 nt 128,124,027 downstream of the HPV18 integration site was used for polyadenylation of the virus-host fusion RNA and production of three RNA isoforms via alternative RNA splicing. See other details in (D).