Abstract:Natural variants of human papillomavirus (HPV) are classified into lineages and sublineages based upon whole-genome sequence, but the impact of diversity on protein function is unclear. We investigated the susceptibility of 3–8 representative pseudovirus variants of HPV16, HPV18, HPV31, HPV33, HPV45, HPV52, and HPV58 to neutralization by nonavalent vaccine (Gardasil®9) sera. Many variants demonstrated significant differences in neutralization sensitivity from their consensus A/A1 variant but these were of a lo… Show more
“…Among the four HPV16 lineages, lineage D contained the largest number of different glycosylation sites in L1 and L2 proteins from lineage A ( Figure 2 ). Godi et al showed that compared with HPV16 lineage A, lineages B, C, and D exhibited slightly (<2-fold) reduced sensitivity to nonavalent vaccine sera [ 62 ]. The unique glycosylation sites existing on the L1 proteins of lineages B, C and D, especially D, might be one of the determinants accounting for this difference.…”
Human papillomavirus type 16 (HPV16) is the most prevalent HPV type causing cervical cancers. Herein, using 1597 full genomes, we systemically investigated the mutation profiles, surface protein glycosylation sites and the codon usage bias (CUB) of HPV16 from different lineages and sublineages. Multiple lineage- or sublineage-conserved mutation sites were identified. Glycosylation analysis showed that HPV16 lineage D contained the highest number of different glycosylation sites from lineage A in both L1 and L2 capsid proteins, which might lead to their antigenic distances between the two lineages. CUB analysis showed that the HPV16 open reading frames (ORFs) preferred codons ending with A/T. The CUB of HPV16 ORFs was mainly affected by natural selection except for E1, E5 and L2. HPV16 only shared some of the preferred codons with humans, which might help reduce competition in translational resources. These findings increase our understanding of the heterogeneity between HPV16 lineages and sublineages, and the adaptation mechanism of HPV in human cells. In summary, this study might facilitate HPV classification and improve vaccine development and application.
“…Among the four HPV16 lineages, lineage D contained the largest number of different glycosylation sites in L1 and L2 proteins from lineage A ( Figure 2 ). Godi et al showed that compared with HPV16 lineage A, lineages B, C, and D exhibited slightly (<2-fold) reduced sensitivity to nonavalent vaccine sera [ 62 ]. The unique glycosylation sites existing on the L1 proteins of lineages B, C and D, especially D, might be one of the determinants accounting for this difference.…”
Human papillomavirus type 16 (HPV16) is the most prevalent HPV type causing cervical cancers. Herein, using 1597 full genomes, we systemically investigated the mutation profiles, surface protein glycosylation sites and the codon usage bias (CUB) of HPV16 from different lineages and sublineages. Multiple lineage- or sublineage-conserved mutation sites were identified. Glycosylation analysis showed that HPV16 lineage D contained the highest number of different glycosylation sites from lineage A in both L1 and L2 capsid proteins, which might lead to their antigenic distances between the two lineages. CUB analysis showed that the HPV16 open reading frames (ORFs) preferred codons ending with A/T. The CUB of HPV16 ORFs was mainly affected by natural selection except for E1, E5 and L2. HPV16 only shared some of the preferred codons with humans, which might help reduce competition in translational resources. These findings increase our understanding of the heterogeneity between HPV16 lineages and sublineages, and the adaptation mechanism of HPV in human cells. In summary, this study might facilitate HPV classification and improve vaccine development and application.
“…Among the four HPV16 lineages, lineage D contained the largest number of different glycosylation sites in L1 and L2 proteins from lineage A (Figure 1). Godi et al showed that comparing with HPV16 lineage A, lineage B, C, and D exhibited slightly (<2-fold) reduced sensitivity to nonavalent vaccine sera [57]. The unique glycosylation sites existed on the L1 proteins of lineages B, C and D, especially D, might be one of the determinants for this difference.…”
Human papillomavirus type 16 (HPV16) is the most prevalent HPV type causing cervical cancers. Herein, using 1,597 full genomes of HPV16, we systemically investigated the mutation profiles, surface protein glycosylation sites and the codon usage bias of the eight open reading frames (ORFs) of HPV16 genomes from different lineages and sublineages. Multiple lineage- or subline-age-specific mutation sites were identified. Glycosylation analysis showed that HPV16 lineage D contained the highest number of unique potential glycosylation site in both L1 and L2 capsid protein, which might lead to their antigenic distances from other HPV16 lineages. Nucleotide composition of HPV16 showed that the overall AT content was higher than GC content at the 3rd codon position. Relatively high ENC values suggested that the HPV16 ORFs didn't have strong codon usage bias. Most of the HPV16 ORFs were mainly governed by natural selection pressure such as translational pressure, except for L2. HPV16 only shared some of the preferred codons with human, which might help reduce competition in translational resources. These findings may help increase our understanding of the heterogeneity between HPV16 lineages and sublineages, and the adaptation mechanism of HPV in human cells, which might facilitate HPV classification and improve vaccine development and application.
“…The absence of cross-protection against HPV types that belong to both the same and different α-species was also seen for HPV16 and HPV18 in vaccinated women from Costa Rica (Skinner et al, 2016), where HPV31 (α-9) and HPV51 (α-6) infections appeared post-vaccination. Moreover, considering that sublineage variants show significant differences in neutralization sensitivity (Godi et al, 2015;Godi et al, 2019), we examined HPV81 strains, to investigate whether different L1 antigenic variants were present in SI and MI, and whether they might influence their cross-protection properties. Overall, the L1 protein harbored a greater number of variable amino acids than the L2 protein (35 amino-acid vs 9 aminoacid changes, respectively).…”
Section: Discussionmentioning
confidence: 99%
“…β-Turns are very frequently the sites of interactions in proteins and peptides, both because they are topologically biased to occur on the surfaces of proteins, and because their structures present the side chains of corner residues, which are optimal for molecular recognition. The Hamming distance (Hamming, 1986;Farci et al, 2000) was calculated using online software (Hacksparrow, 2019). The Pearson distance and phylogenetic tree were calculated using the MEGA10 software (Kumar et al, 2018).…”
Non-nonavalent vaccine (9v) Human papillomavirus (HPV) types have been shown to have high prevalence among HIV-positive women. Here, 1444 cervical samples were tested for HPV DNA positivity. Co-infections of the 9v HPV types with other HPV types were evaluated. The HPV81 L1 and L2 genes were used to investigate the genetic variability of antigenic epitopes. HPV-positive samples were genotyped using the HPVCLART2 assay. The L1 and L2 protein sequences were analyzed using a self-optimized prediction method to predict their secondary structure. Co-occurrence probabilities of the 9v HPV types were calculated. Non9v types represented 49% of the HPV infections; 31.2% of the non9v HPV types were among the low-grade squamous intraepithelial lesion samples, and 27.3% among the high-grade squamous intraepithelial lesion samples, and several genotypes were low risk. The co-occurrence of 9v HPV types with the other genotypes was not correlated with the filogenetic distance. HPV81 showed an amino-acid substitution within the BC loop (N75Q) and the FGb loop (T315N). In the L2 protein, all of the mutations were located outside antigenic sites. The weak cross-protection of the 9v types suggests the relevance of a sustainable and effective screening program, which should be implemented by HPV DNA testing that does not include only high-risk types.
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