Genetic diversity and functional implication of the long control region in human papillomavirus types 52, 58, and 16 from Central China

Object: High-risk human papillomavirus (HR-HPV) is a main reason for cervical cancer. The long control region (LCR) of the genome plays a variety of roles in the transcription of the virus.Methods: LCR sequences were amplified by polymerase chain reaction (PCR) and confirmed by DNA sequencing. MEGA 11.0 software and NCBI blast were used to analyze the sequences and construct the Neighbor-Joining tree. In addition, the JASPAR database was used to predict the potential transcription factor binding sites (TFBS).Results: For HPV-52 LCR, 68 single nucleotide polymorphisms (SNPs), 8 deletions, and 1 insertion were found, 17 of which were novel variations. Most of the variants were clustered in B2 sub-lineage (96.22%). For HPV-58 LCR, 25.43% of samples were prototype. 49 SNPs, 2 deletions, and 1 insertion were observed in the remaining samples. A1 sub-lineage was the most frequent (64.16%). For HPV-16 LCR, 75 SNPs and 2 deletions were identified, 13 of which were newly identified. A total of 55.68% of the variants were distributed in A4 sub -lineage. The JASPAR results suggested that multiple variations occurred in TFBSs, which might affect the function of transcription factors.Conclusions: This study provides experimental data for further studies on the epidemiology and biological function of LCR. Various LCR mutational data may prove useful for exploring the carcinogenic mechanism of HPV.