Global genomic diversity of human papillomavirus type 6 (HPV6): a comparative analysis of 724 isolates and 190 complete genome sequences

MATEJA M. JELEN; ZIGUI CHEN; BOTJAN J. KOCJAN; SEME K; FELICITY J. BURT; PAUL K.S. CHAN; CHOUHY DIEGO; CATHARINA E. COMBRINCK; FRANCOIS COUTLEE; CHRISTINE ESTRADE; ALEX FERENCZY; ALISON FIANDER; EDUARDO L. FRANCO; SUZANNE M. GARLAND; ADRIANA A GIRI; JOAQUÍN VÍCTOR GONZÁLEZ; GRÖNING A; KERSTIN HEIDRICH; SAM HIBBITTS; HONJAK L; TOMMY N.M. LUK; KARINA MARINIC; TOSHIHIKO MATSUKURA; ANNA NEUMANN; OTRBENK A; PICCONI MA; RICHARDSON H; SAGADIN M; SAHLI R; SEEDAT RY; SEVERINI A; SINCHI JL; SMAHELOVA J; TABRIZI SN; TACHEZY R; TOHME S; ULOZA V; VITKAUSKIENE A; WONG YW; ZIDOVEC LEPEJ S; BURK RD; POLJAK M

Conferencia; 29th International Papillomavirus Conference and Public Health & Clinical Workshops; 2014

Background: HPV6 is the major etiological agent of anogenital warts and laryngeal papillomas. Geographical and clinical associations of globally circulating HPV6 variants have never been clearly evaluated. Objetives: To characterize the global genomic diversity of HPV6 and explore geographical and clinical associations of HPV6 genome variants. Methods: In total, 530 HPV6 isolates from the anogenital region (179 anogenital warts, 186 cervical swabs, 35 unspecified), head and neck region (83 laryngeal papillomas, 1 nasal papilloma) and from unspecified anatomical sites (46 isolates) from 14 countries (six continents) were sequenced in four regions: E5a-E5b-L1-LCR. Isolates with unique single nucleotide polymorphisms (SNPs), indels and amino acid changes were fully sequenced. Global and pairwise alignments were used for nucleotide difference calculation, maximum likelihood (RAxML) phylogenetic tree construction, lineage/sublineage assignment and identification of (sub) lineage specific SNPs. Geographical and clinical associations were statistically evaluated on 724 HPV6 isolates obtained from our study and GenBank. Results: 492/530 HPV6 isolates were successfully sequenced in E5a-E5b-L1-LCR regions; of them, 130 were fully sequenced. Pairwise heterogeity of 190 HPV6 complete genomes (130 from our study, 60 from GenBank) was 1.6%. Open reading frames (ORFs) differed in nucleotide diversity, froom 13.2% (E5b) to least 3.4% (E7). Global phylogenetic tree revealed two lineages (A and B) and five B sublineages: B1-B5. A 960-bp region within L2 ORF was disignated as the representative region for complete-genome-based phylogenetic clustering. Significant (p