Intratype sequence variation among clinical isolates of the human papillomavirus type 6 L1 ORF: clustering of mutations and identification of a frequent amino acid sequence variant.

Abstract

Human papillomavirus type 6 (HPV-6) is the causative agent of condyloma acuminata, a common sexually transmitted disease. Virus-like particles (VLPs) assembled from the L1 major capsid protein represent promising candidates for prophylactic vaccines. However, any intratype sequence variation among HPV-6 L1 ORFs will influence which sequence is used for a vaccine according to its prevalence in the population and its propensity for VLP production. Therefore, we have analysed the entire L1 nucleotide sequence of 17 clinical isolates of HPV-6 from the London area. We found 28 positions where changes from the prototype HPV-6b L1 occurred, showing that HPV-6 L1 intratype variation is greater than previously reported. The most frequently observed substitutions are clustered into three discrete regions : R 1 (nt 5920-6075), R 2 (nt 6590-6670) and R 3 (nt 7070-7230). Indeed, most of the nucleotide substitutions within the HPV-6 L1 reported worldwide also map to these regions. The R3 region contains predominantly non-silent substitutions, the most common of which is a G-to-C substitution at position 7079. This results in a Glu-to-Gln change at aa 431, although this change had no effect on VLP yield or stability. This substitution defines a new HPV-6 L1 amino acid sequence that is more abundant in the isolates examined than any other reported sequence.

Synthetic multi‐epitope peptides identified in silico induce protective immunity against multiple influenza serotypes

“…However, over time, point mutations tend to accumulate in regions of the genome where they may or may not be biologically advantageous, but where they are certainly not disadvantageous, as that would result in the extinction of that virus line. Following this principle, it has been possible to define heterogeneic areas not only in variable viruses such as HIV [22], but also in highly stable viruses such as human papillomavirus [23]. Multiple sequence alignment of available influenza protein sequences is an appropriate method for the identification of such variable regions.…”

Humoral Immune Response Recognizes a Complex Set of Epitopes on Human Papillomavirus Type 6 L1 Capsomers

“…Chen also examined the L1 sequence of 49 HPVs, and although there is a hot spot of variability in the C terminus, the majority of the C terminus seems to be conserved, likely for structural reasons (7). One study characterizing HPV6 L1 variation among 17 clinical isolates showed that despite genetic variations clustering in three regions of L1, a nonsilent mutation, Glu3Gln at residue 431 of the C terminus, was the most frequently found (3). If the C terminus played a significant role in antibody binding it would be expected to have a greater degree of divergence resulting from evolutionary pressures selecting residue changes that evade the host immune response.…”

Human papillomavirus type 16 molecular variants in Guarani Indian women from Misiones, Argentina

“…8 For all HPV types studied to date, intratypic variants have been identified. [9][10][11][12] These variants differ from the reference viral type sequence in the L1 coding region by up to 2.0% and show different geographic distribution. 13 In particular, HPV16 variants are distributed differently among the five continents: Asian (A) variants are mainly in Southeast Asia, African (Af) variants are mainly in Africa, European (E) variants are in all regions other than Africa, and Asian-American (AA) variants are located mainly in Central, South America and Spain.…”