Determination of the complete genome and functional analysis of HPV6 isolate VBD19/10 from a patient with aggressive recurrent respiratory papillomatosis.

Human papillomavirus (HPV) types 6 and 11 are the aetiological agent of recurrent respiratory papillomatosis (RRP). The complete genome of an HPV6 isolate with a 170 base pair (bp) duplication identified within the long control region (LCR) from a patient with aggressive recurrent respiratory papillomatosis was determined. The promoter sequence from the HPV LCR including the 170 bp duplication was placed upstream of a heterologous reporter gene and the activity of the reporter gene product determined using transfected cells. In total, mutations were observed at 157 nucleotide positions of the complete genome and included nucleotide substitutions, deletions and insertions, resulting in amino acid changes at 43 residue positions. Reporter gene activity using an HPV-derived LCR region with a 170 bp duplication was significantly higher than that using an HPV-derived LCR region with no duplication within this region. The results suggest that novel HPV variants warrant further investigation for potential biomarkers of aggressive disease.

Novel HPV-6 variants of human papillomavirus causing recurrent respiratory papillomatosis in southern Africa.

There is currently no information regarding the genetic diversity of HPV-6 variants circulating in South Africa. The aim of this study was to determine the HPV-6 variants affecting patients with recurrent respiratory papillomatosis, to determine whether mutations correlate with disease severity and identify molecular determinants of virulence with prognostic relevance. HPV-6 variants were identified based on genome changes within the 712-991 bp region encompassing the non-coding region (URR) of the genome, with variations in length resulting from insertions and duplications, and the 453-bp gene encoding the E6 protein. Based on manual comparison of sequence data from the URR, the isolates were identified as HPV-6a and HPV-6vc variants. Three novel HPV-6 variants were identified: one based on a mutation in the E6 region; two based on changes in the URR including a unique substitution detected in three isolates and an insertion and 170-bp duplication in the URR genome in one patient, who had clinical features of severe disease.