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.

Phylogenetically related, clinically different: human papillomaviruses 6 and 11 variants distribution in genital warts and in laryngeal papillomatosis

“…However, previous research did not identify geographical origin as an important component of viral diversity for HPV6 and HPV11. Heinzel and co‐workers communicated a global study of these two HPVs , including 19 samples containing HPV6 and ten samples containing HPV11. More recently, de Matos et al .…”

“…Based on this criterion, HPV6 and HPV11 variant lineages have been described . Several studies have addressed the genetic diversity of HPV6 and HPV11 , and some of them have aimed to establish a link between genetic variation and differential outcome of the infection .…”

Genome variation of human papillomavirus types: Phylogenetic and medical implications

“…If HPVs had diversified recently in humans, one would expect to find a spectrum of intermediate HPV genomes represented in addition to the known HPV types. However, comparison of thousands of HPV isolates has failed to identify a single genome that is intermediate to any pair of even the most closely related HPV types, namely, HPV‐2/27, 6/11 and 18/45 16, 17, 18. Instead, each HPV type is an isolated taxonomic unit, represented by a small number (up to 100) of closely related molecular variants.…”

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

“…from random mutational events and several variation sites were shared by several isolates and variants [Ho et al, 1993;Ong et al, 1993;Heinzel et al, 1995;Yamada et al, 1997;Giannoudis and Herrington, 2001;Nindl, 2002;Aho et al, 2003;Calleja-Macias et al, 2004;Gagnon et al, 2004;Prado et al, 2005;Bernard et al, 2006]. The genetic variation of up to 1.1% between the most divergent L1 variants for each type corresponds to the expected degree of diversity within an HPV type in a coding sequence.…”