Intra-host sequence variability in human papillomavirus
Journal article, Peer reviewed
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Original versionMandishora RSD, Gjøtterud K, Lagström SL, Stray-Pedersen B, Duri K, Chin'ombe N, Nygård M, Christiansen IK, Ambur OH, Chirenje MZ, Rounge TB. Intra-host sequence variability in human papillomavirus. Papillomavirus Research. The Journal of HPV and other Small DNA Tumor Viruses. 2018;5:180-191 http://dx.doi.org/10.1016/j.pvr.2018.04.006
Human papillomaviruses (HPVs) co-evolve slowly with the human host and each HPV genotype displays epithelial tropisms. We assessed the evolution of intra HPV genotype variants within samples, and their association to anogenital site, cervical cytology and HIV status. Variability in the L1 gene of 35 HPV genotypes was characterized phylogenetically using maximum likelihood, and portrayed by phenotype. Up to a thousand unique variants were identiﬁed within individual samples. In-depth analyses of the most prevalent genotypes, HPV16, HPV18 and HPV52, revealed that the high diversity was dominated by a few abundant variants. This suggests high intra-host mutation rates. Clades of HPV16, HPV18 and HPV52 were associated to anatomical site and HIV co-infection. Particularly, we observed that one HPV16 clade was speciﬁc to vaginal cells and one HPV52 clade was speciﬁc to anal cells. One major HPV52 clade, present in several samples, was strongly associated with cervical neoplasia. Overall, our data suggest that tissue tropism and HIV immunosuppression are strong shapers of HPV evolution.