Author/Editor     Jelen, Mateja; Chen, Zigui; Kocjan, Boštjan; Hošnjak, Lea; Oštrbenk, Anja; Seme, Katja; Židovec-Lepej, Snježana; Poljak, Mario
Title     Global genomic diversity of human papillomavirus type 6 (HPV6) based on 724 isolates and 190 complete genome sequences
Type     članek
Vol. and No.     Letnik 88, št. 13
Publication year     2014
Volume     str. 7307-7316
ISSN     0022-538X - Journal of virology
Language     eng
Abstract     Human papillomavirus type 6 (HPV6) is the major etiological agent of anogenital warts and laryngeal papillomas and has been included in both the quadrivalent and nonavalent prophylactic HPV vaccines. This study investigated global genomic diversity of HPV6 on 724 isolates and 190 complete genomes from six continents and the association of HPV6 genomic variants with geographical location, anatomical site of infection/disease and gender. Initially, a 2,800 bp E5a-E5b-L1-LCR fragment was sequenced from 492/530 (92.8%) HPV6 positive samples collected for this study. Out of them, 130 exhibited at least one single nucleotide polymorphisms (SNP), indel or amino acid change in the E5a-E5b-L1-LCR fragment and were sequenced in full-length. A global alignment and maximum likelihood tree of 190 HPV6 complete genomes (130 fully sequenced in this study and 60 from sequence repositories) revealed two variant lineages: A and B, and five B sublineages: B1, B2, B3, B4 and B5. HPV6 (sub)lineage-specific SNPs and a 960-bp representative region for whole-genome-based phylogenetic clustering within L2 open reading frame were identified. Multivariate logistic regression analysis revealed that lineage B predominated globally. Sublineage B3 was more common in Africa and North and South America and lineage A in Asia. Sublineages B1 and B3 were associated with anogenital infections, indicating a potential lesion-specific predilection of some HPV6 sublineages. Females had higher odds for infection with sublineage B3 than males. In conclusion, global HPV6 phylogenetic analysis revealed the existence of two variant lineages and five sublineages, showing some degree of ethnogeographic, gender and/or disease predilection in their distribution. IMPORTANCE: This study established the largest database of globally circulating HPV6 genomic variants and contributed a total of 130 new HPV6 complete genome sequences to available sequence repositories. Two HPV6 variant lineages and five sublineages were identified and showed some degree of association with geographical location, anatomical site of infection/disease and/or gender. We additionally identified several HPV6 lineage and sublineage-specific SNPs to facilitate the identification of HPV6 variants and determined a representative region within L2 gene suitable for HPV6 whole-genome-based phylogenetic analysis. This study complements and significantly expands the current knowledge of HPV6 genetic diversity and forms a comprehensive basis for future epidemiological, evolutionary, functional, pathogenicity, vaccination and molecular assay development studies.
Keywords     human papillomavirus
genomic diversity
anogenital warts
človeški papiloma virus
genomske raznolikosti
anogenitalne bradavice