Genetic variation of E6 and E7 genes of human papillomavirus type 16 from central China

Abstract

Background Persistent high-risk human papillomavirus (HR-HPV) infection is an important factor in the development of cervical cancer, and human papillomavirus type 16 (HPV-16) is the most common HR-HPV type worldwide. The oncogenic potential of HPV-16 is closely related to viral sequence variation. Methods In order to clarify the variant characteristics of HPV-16 E6 and E7 genes in central China, E6 and E7 sequences of 205 HPV‐16 positive samples were amplified by polymerase chain reaction. PCR products of E6 and E7 genes were further sequenced and subjected to variation analysis, phylogenetic analysis, selective pressure analysis and B-cell epitope prediction. Results Twenty-six single nucleotide variants were observed in E6 sequence, including 21 non-synonymous and 5 synonymous variants. Twelve single nucleotide variants were identified in E7 sequence, including 6 non-synonymous and 6 synonymous variants. Four new variants were found. Furthermore, nucleotide variation A647G (N29S) in E7 was significantly related to the higher risk of HSIL and cervical cancer. Phylogenetic analysis showed that the E6 and E7 sequences were all distributed in A lineage. No positively selected site was found in HPV-16 E6 and E7 sequences. Non-conservative substitutions in E6, H31Y, D32N, D32E, I34M, L35V, E36Q, L45P, N65S and K75T, affected multiple B-cell epitopes. However, the variation of E7 gene had little impact on the corresponding B-cell epitopes (score < 0.85). Conclusion HPV-16 E6 and E7 sequences variation data may contribute to HR-HPV prevention and vaccine development in Jingzhou, central China.

Phylogenetic analysis and antigenic epitope prediction for E6 and E7 of Alpha-papillomavirus 9 in Taizhou, China

“…However, there were no reports of positive selection sites for HPV58 E6 in China [ 33 – 36 ]. No positive selection sites for HPV16 E6 and E7 genes have been reported in central China [ 37 ]. No positive selection sites for HPV52 E6 and E7 genes have been reported in central and Southwest China [ 38 , 39 ].…”

“…Therefore, the substitution of the positive selection site D32E in HPV16 E6 influences its antigenic epitopes, which may make it more difficult to detect by the immune system, thereby enhancing adaptability of HPV to the environment. In addition, Li et al [ 37 ] suggested that non-conservative substitutions of amino acids should be fully considered when developing therapeutic vaccines, such as H31Y, D32N, D32E, I34M, L35V, E36Q, L45P, N65S, and K75T in HPV16 E6. Chen et al [ 33 ] suggested that K93N in HPV33 E6, Q97L in HPV33 E7, R145K in HPV58 E6, and T20I in HPV58 E7 belong to ideal B-cell epitopes.…”