Abstract
BackgroundCervical cancer is associated with infection by certain subtypes of human papillomavirus (HPV). The L1 protein comprising HPV vaccine formulations elicits high-titre neutralizing antibodies and confers protection against specific HPV subtypes. HPV L2 protein is an attractive candidate for cross-protective vaccines. HPV-33 and HPV-58 are very prevalent among Chinese women.MethodsTo study the gene intratypic variations and polymorphisms of HPV-33 and HPV-58 L1/L2 in Sichuan China, HPV-33 and HPV-58 L1 and L2 genes were sequenced and compared with other genes submitted to GenBank. Phylogenetic trees were constructed by maximum-likelihood and the Kimura 2-parameters methods (MEGA 6). The secondary structure was analyzed by PSIPred software, and HPV-33 and HPV-58 L1 homology models were created by SWISS-MODEL software. The selection pressures acting on the L1/L2 genes were estimated by PAML 4.8.ResultsAmong 124 HPV-33 L1 sequences 20 single nucleotide mutations were observed included 8/20 non-synonymous and 12/20 synonymous mutations. The 101 HPV-33 L2 sequences included 12 single nucleotide mutations comprising 7/12 non-synonymous and 5/12 synonymous mutations. The 223 HPV-58 L1 sequences included 32 single nucleotide mutations comprising 9/32 non-synonymous and 23/32 synonymous mutations. The 201 HPV-58 L2 sequences comprised 26 single nucleotide mutations including 9/26 non-synonymous and 17/26 synonymous mutations. Selective pressure analysis showed that most of the common non-synonymous mutations showed a positive selection. HPV-33 and HPV-58 L2 were more stable than HPV-33 and HPV-58 L1.ConclusionsHPV-33 and HPV-58 L2 were better candidates as clinical diagnostic targets compared with HPV-33 and HPV-58 L1. Clinical diagnostic probes and second-generation polyvalent vaccines should be designed on the basis of the unique sequence of HPV-33 and 58 L1/L2 variations in Sichuan, to improve the accuracy of clinical detection and the protective efficiency of vaccines.Electronic supplementary materialThe online version of this article (doi:10.1186/s12985-016-0629-9) contains supplementary material, which is available to authorized users.
Highlights
Cervical cancer is associated with infection by certain subtypes of human papillomavirus (HPV)
Of all the HPV-58 and HPV-33 samples, only 223 sequences of HPV-58 L1 gene, 201 sequences of the HPV-58 L2 gene, 124 sequences of the HPV-33 L1 gene, and 101 sequences of the HPV-33 L2 gene were obtained owing to the small number of copies of infected HPV in some women and limited amplicons obtained for sequencing, and there maybe a potential sampling bias against integrated HPV genomes resulting in lost capsid genes
Gene polymorphism of HPV-33 L1 Compared with the HPV-33 reference sequence (GenBank: M12732.1), the nucleotide variation rate of HPV33 L1 was 68.55 % (85/124) in the 124 HPV-33 L1 sequences studied
Summary
Cervical cancer is associated with infection by certain subtypes of human papillomavirus (HPV). The L1 protein comprising HPV vaccine formulations elicits high-titre neutralizing antibodies and confers protection against specific HPV subtypes. HPV-33 and HPV-58 are very prevalent among Chinese women. Human papillomavirus (HPV) infection plays a critical role in the development of cervical cancer [1]. The risk of developing cervical cancer in HPV-infected patients is 50-fold higher than in uninfected women [1, 2]. High-risk oncogenic HPV subtypes −16, −18, −58, −33, −52 and −45 are more common in Asia than elsewhere [5]. HPV-33 and HPV-58 are prevalent among Chinese women, only after HPV-16 [6,7,8]. Compared with the highrisk HPV-18, vaccine design in China is focused predominantly on high-risk subtypes HPV-58, and HPV-33
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