title: Variation of human papillomavirus type 6 (HPV-6) and HPV-11 genomes sampled throughout the world.
abstract: We examined the genomic diversity of human papillomavirus type 6 (HPV-6) and HPV-11 isolates from different parts of the world by comparing the nucleotide sequences of part of the long control region of three reference clones and 62 HPV-6 and 40 HPV-11 isolates from Africa, Europe, Asia, and North and South America. The genomic sequence of the HPV-6b reference type had to be amended by inclusion of a 94-bp segment, which is also present with minor differences in HPV-6a. Aside from two small inserts typical of all variants related to HPV-6a and three inserts found in HPV-11 variants, no major alterations to the size of the long control regions of these viruses were observed. This corrects the previous impression that these two HPV types are highly polymorphic. Altogether, 19 HPV-6 and 10 HPV-11 variant genomes could be distinguished, and most of the differences were due to point substitutions. The variants of either type were continuously connected in phylogenetic trees rather than clustered separately into subtype groups. Thirteen mutations, namely, the two HPV-6a inserts and 11 substitutions in HPV-6 or HPV-11 variants, reduced the dissimilarity between the types, but they bridged only a small fraction of the genetic distance between the two types. Genomes more obviously intermediate between HPV-6 and HPV-11 were not found and probably do not exist any more. A single HPV-11 variant was found in Africa, but otherwise, no significant correlations of HPV-6 or HPV-11 variants with geography or ethnicity of the patient cohort were found. Functional analysis of diverse enhancer variants showed activities that differed two-to threefold, and it must be considered that transcriptional differences may alter the biology or pathology of these viruses. Similar variants were found in lesions from anatomically different sites and in both benign and malignant lesions.
authors.affiliation: Laboratory for Papillomavirus Biology, National University of Singapore.
authors.forename: P A
authors.initials: PA
authors.lastname: Heinzel
authors.forename: S Y
authors.initials: SY
authors.lastname: Chan
authors.forename: L
authors.initials: L
authors.lastname: Ho
authors.forename: M
authors.initials: M
authors.lastname: O'Connor
authors.forename: P
authors.initials: P
authors.lastname: Balaram
authors.forename: M S
authors.initials: MS
authors.lastname: Campo
authors.forename: K
authors.initials: K
authors.lastname: Fujinaga
authors.forename: N
authors.initials: N
authors.lastname: Kiviat
authors.forename: J
authors.initials: J
authors.lastname: Kuypers
authors.forename: H
authors.initials: H
authors.lastname: Pfister
mesh_terms: D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D004279:DNA, Viral / Q000235:genetics; D004742:Enhancer Elements, Genetic; D005006:Ethnicity; D014644:Genetic Variation; D016679:Genome, Viral; D006801:Humans; D017720:Molecular Epidemiology; D008969:Molecular Sequence Data; D009154:Mutation; D027383:Papillomaviridae / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification; D030361:Papillomavirus Infections / Q000453:epidemiology / Q000821:virology; D010802:Phylogeny; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D012689:Sequence Homology, Nucleic Acid; D014412:Tumor Virus Infections / Q000453:epidemiology / Q000821:virology
chemical_list: D017931:DNA Primers; D004279:DNA, Viral