Cancer, warts, or asymptomatic infections: clinical presentation matches codon usage preferences in human papillomaviruses

  • Viruses rely completely on the hosts' machinery for translation of viral transcripts. However, for most viruses infecting humans, codon usage preferences (CUPrefs) do not match those of the host. Human papillomaviruses (HPVs) are a showcase to tackle this paradox: they present a large genotypic diversity and a broad range of phenotypic presentations, from asymptomatic infections to productive lesions and cancer. By applying phylogenetic inference and dimensionality reduction methods, we demonstrate first that genes in HPVs are poorly adapted to the average human CUPrefs, the only exception being capsid genes in viruses causing productive lesions. Phylogenetic relationships between HPVs explained only a small proportion of CUPrefs variation. Instead, the most important explanatory factor for viral CUPrefs was infection phenotype, as orthologous genes in viruses with similar clinical presentation displayed similar CUPrefs. Moreover, viral genes with similar spatiotemporal expression patterns also showed similar CUPrefs. Our results suggest that CUPrefs in HPVs reflect either variations in the mutation bias or differential selection pressures depending on the clinical presentation and expression timing. We propose that poor viral CUPrefs may be central to a trade-off between strong viral gene expression and the potential for eliciting protective immune response.

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Author:Marta Félez-Sánchez, Jan-Hendrik Trösemeier, Stéphanie Bedhomme, Maria Isabel González-Bravo, Christel KampORCiDGND, Ignacio G. Bravo
Pubmed Id:
Parent Title (English):Genome biology and evolution
Publisher:Oxford Univ. Press
Place of publication:Oxford
Document Type:Article
Date of Publication (online):2015/07/01
Date of first Publication:2015/07/01
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2016/08/24
Tag:acute infection; cancer; chronic infection; clinical presentation; codon usage preferences; genotype–phenotype; human viruses; immune system; mutation; translational selection; warts
Page Number:19
First Page:2117
Last Page:2135
(c)The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (, which permits
non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact
Institutes:Informatik und Mathematik / Informatik
Dewey Decimal Classification:0 Informatik, Informationswissenschaft, allgemeine Werke / 00 Informatik, Wissen, Systeme / 004 Datenverarbeitung; Informatik
6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (English):License LogoCreative Commons - Namensnennung-Nicht kommerziell 4.0