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. 2022 May 29:31:101286.
doi: 10.1016/j.bbrep.2022.101286. eCollection 2022 Sep.

Genetic diversity of E6, E7 and the long control region in human papillomavirus type 16 variants in Beijing, China

Jiao Wang  1 , Yifan Guo  2 , Hui Wang  1 , Ying Li  1 , Li Zhang  1 , Zhan Wang  1 , Lei Song  3 , Hongtu Liu  1   4   5
Affiliations

Genetic diversity of E6, E7 and the long control region in human papillomavirus type 16 variants in Beijing, China

Jiao Wang et al. Biochem Biophys Rep. .

Abstract

Background: High-risk human papillomavirus type 16 (HPV16) is a risk factor for cervical cancer. The progression from initial infection to cervical cancer has been linked to properties of the viral sequences. However, the distribution of HPV16 variants among Chinese women has not been extensively addressed and the role of HPV16 variants in the risk of cervical carcinogenesis remains poorly understood.

Methods: HPV16 positive cervical exfoliated cell samples were collected from 249 women living in Beijing, China. PCR products from two fragments of E6-E7 and LCR of HPV16 in these samples were sequenced and analyzed.

Results: Lineage A was found in the subjects, including A1, A2, A3 and A4 sublineages. Based on the HPV16 reference sequences, 26 nucleotide mutations of A4 sublineage and 39 nucleotide mutations of A1-3 sublineages were found in the E6, E7 and LCR of HPV16 isolates. Point mutations T843C, A7287C and A7872G of A4 sublineage were significantly associated with high-grade cervical lesions. The high-frequency sites in HPV16 LCR located at regions that can bind to multiple transcription factors.

Conclusions: This study contributes to the identification of unique variants in the E6, E7 and LCR of HPV16 isolates infected in Chinese women. Mutations of T843C, A7287C and A7872G in A4 sublineages were significantly associated with high-grade cervical lesions, suggesting that mutations in the E7 and LCR region have potential effects on viral replication and progression of cervical cancer.

Keywords: E6; E7; HPV16; LCR; Phylogeny; Polymorphism.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Fig. 1
Fig. 1
Phylogenetic tree of the HPV16 variants based on E6E7 and LCR sequences. A. Phylogenetic tree based on 98 E6E7 sequences. B. Phylogenetic tree based on 84 LCR sequences. The Neighbor-Joining method and the Tamura 3-Parameter model were used to construct the phylogenetic tree by MEGA version 7.0. The standard sequences included NC_001526.4, K02718 (A1), AF536179 (A2), HQ644236 (A3), AF534061 (A4), AF536180 (B1), AF472509 (C1) and AF402678 (D3). Numbers closest to the branch points are bootstrap values (1,000 replicates). Both E6E7 and LCR sequences of 41 samples were marked in red. . (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)
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