Polymorphism of the capsid L1 gene of human papillomavirus types 31, 33, and 35

Cornut, Gilbert; Gagnon, Simon; Hankins, Catherine; Money, Deborah; Pourreaux, Karina; Franco, Eduardo L.; Coutlée, François

doi:10.1002/jmv.21777

Cited by 19 publications

(14 citation statements)

References 53 publications

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“…1 Clinical relevance of HPV31 variants has been rarely described, [13][14][15] although the intratypic variations in the L1, E6, E7 and long control region were recognized. [14][15][16][17][18][19][20][21] A recent study by Chen et al 22 has defined HPV31 variants as A, B and C lineages based on the whole genome analyses. This provides a basis to view the variant as a distinct phylogenetic entity and better understand the variant-related pathogenesis of cervical lesion.…”

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confidence: 99%

Association of human papillomavirus type 31 variants with risk of cervical intraepithelial neoplasia grades 2–3

Schiffman

Koutsky

et al. 2012

Intl Journal of Cancer

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Although the lineages of human papillomavirus type 31 (HPV31) variants are recognized, their clinical relevance is unknown. The purpose of our study was to examine risk of cervical intraepithelial neoplasia Grades 2-3 (CIN2/3) by HPV31 variants. Study subjects were women who participated in the atypical squamous cells of undetermined significance and low-grade squamous intraepithelial lesion Triage Study and who had HPV31 infections detected at one or more visits. They were followed semi-annually over 2 years for detection of HPV DNA and cervical lesion. HPV31 isolates were characterized by DNA sequencing and assigned into 1 of 3 variant lineages. CIN2/3 was histologically confirmed in 127 (27.0%) of the 470 HPV31-positive women, 83 diagnosed at the first HPV31-positive visit and 44 thereafter. The odds ratio for the association of 2-year cumulative risk of CIN2/3 was 1.7 (95% CI: 1.0-2.9) for infections with A variants and 2.2 (95% CI: 1.2-3.9) for infections with B variants as compared to those with C variants. Among women without CIN2/3 at the first HPV31-positive visit, the risk of subsequent CIN2/3 was 2.2-fold greater for those with A variants (95% CI: 1.0-4.8) and 2.0-fold greater for those with B variants (95% CI: 0.9-4.9) as compared to those with C variants. Similar associations were observed when CIN3 was used as the endpoint. The findings from our study help to tag HPV31 variants that differ in risk of CIN2/3 and to explain in part why some HPV31 infections regress spontaneously and others lead to disease progression.Cervical infection with human papillomavirus (HPV) types is a necessary cause of cervical cancer and its precursor, cervical intraepithelial neoplasia Grades 2-3 (CIN2/3). 1-3 To date, >150 papillomavirus types have been fully characterized and classified, from the higher to lower taxon, as genera, species and type. 4,5 HPV types are known to differ in their tropisms and oncogenic potentials. Studies of the intratypic variation, i.e., the variant, a level below the taxon of type, have focused mainly on HPV16 and HPV18, showing that some variants were more aggressive than others. [6][7][8][9][10][11][12] HPV31 is one of the oncogenic types, most closely related to HPV16. Prevalence of some HPV types may vary geographically. Results from a recent meta-analysis (including 215 studies worldwide) have shown that on average prevalence of HPV31 infection ranks fourth, after types 16, 18 and 45, in cases of cervical cancer and second, only after type 16, in women with high-grade squamous intraepithelial lesion (referring both to cytologically detected high-grade lesions and histologically diagnosed CIN2/3 or carcinoma in situ in this analysis). 1 Clinical relevance of HPV31 variants has been rarely described, 13-15 although the intratypic variations in the L1, E6, E7 and long control region were recognized. 14-21 A recent study by Chen et al. 22 has defined HPV31 variants as A, B and C lineages based on the whole genome analyses. This provides a basis to view the variant as a distinct phylogenet...

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Association of human papillomavirus type 31 variants with risk of cervical intraepithelial neoplasia grades 2–3

Schiffman

Koutsky

et al. 2012

Intl Journal of Cancer

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“…The L1 gene (bp 5443 to 7119 [40] or the FG loop region from bp 6141 to 6476; numbered according to the HPV31 reference sequence with GenBank accession number J04353) and the L2 gene (bp 3921 to 5725) were amplified with Platinum Taq high-fidelity DNA polymerase (Life Technologies) and sequenced using an ABI 3730 genetic analyzer. Sequence data were collated using DNAS-TAR Lasergene (v9.0) software (DNASTAR, Inc.).…”

Section: Study Samplesmentioning

confidence: 99%

Naturally Occurring Capsid Protein Variants of Human Papillomavirus Genotype 31 Represent a Single L1 Serotype

Bissett

Godi

Fleury

et al. 2015

J Virol

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We investigated naturally occurring variation within the major (L1) and minor (L2) capsid proteins of oncogenic human papillomavirus (HPV) genotype 31 (HPV31) to determine the impact on capsid antigenicity. L1L2 pseudoviruses (PsVs) representing the three HPV31 variant lineages, variant lineages A, B, and C, exhibited comparable particle-to-infectivity ratios and morphologies. Lineage-specific L1L2 PsVs demonstrated subtle differences in susceptibility to neutralization by antibodies elicited following vaccination or preclinical L1 virus-like particle (VLP) immunization or by monoclonal antibodies; however, these differences were generally of a low magnitude. These data indicate that the diagnostic lineage-specific single nucleotide polymorphisms within the HPV31 capsid genes have a limited effect on L1 antibody-mediated neutralization and that the three HPV31 variant lineages belong to a single L1 serotype. These data contribute to our understanding of HPV L1 variant antigenicity. IMPORTANCEThe virus coat (capsid) of the human papillomavirus contains major (L1) and minor (L2) capsid proteins. These proteins facilitate host cell attachment and viral infectivity and are the targets for antibodies which interfere with these events. In this study, we investigated the impact of naturally occurring variation within these proteins upon susceptibility to viral neutralization by antibodies induced by L1 VLP immunization. We demonstrate that HPV31 L1 and L2 variants exhibit similar susceptibility to antibody-mediated neutralization and that for the purposes of L1 VLP-based vaccines, these variant lineages represent a single serotype. Human papillomaviruses (HPVs) have a double-stranded DNA genome of approximately 8 kb which is replicated via host cell polymerases with an error rate of ca. 2 ϫ 10 Ϫ8 base substitutions per site per year (1), substantially lower than that found in the majority of single-stranded RNA viruses (ca. 1 ϫ 10 Ϫ3 base substitutions per site per year) (2). Despite the low evolutionary rate of the HPV genome, variants have arisen over time, leading to the generation of distinct intragenotype lineages classified by a sequence difference of 1 to 10% across the whole genome (3). The single nucleotide polymorphisms (SNPs) that allow segregation of these variants into distinct lineages can be found in each gene/ region, with the highest number accumulating in the noncoding regions (NCR1, NCR2, and URR) and the lowest number accumulating in structural (L1 and L2) genes (4).The HPV structural genes encode the major (L1) and minor (L2) proteins that form the nonenveloped icosahedral viral capsid, which comprises 72 pentameric L1 capsomers, and each capsomer has an upper estimate of one L2 protein (5). The L1 protein mediates attachment to host cells (6), while the L2 protein is essential for subsequent viral infectivity (7).The humoral immune response following natural HPV infection predominately targets conformational epitopes on the surface-exposed loop regions of the L1 protein (8, 9). Seroconvers...

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“…The oncogenesis process is mainly associated with different viral oncoprotein expressions, which are involved in cell transformation [7, 12, 19, 29]. The accuracy of diagnostic processes and the distribution of the different viral types [14, 26, 30–32] indicate which types and variants deserve the special attention [8, 9, 25, 33, 34]. The expression and characterization of recombinant viral oncoproteins are required to obtain biotechnological products as antibodies and potential vaccines [9, 15, 35–37].…”

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confidence: 99%