title: Cancer, Warts, or Asymptomatic Infections: Clinical Presentation Matches Codon Usage Preferences in Human Papillomaviruses.
abstract: 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.
authors.affiliation: Infections and Cancer Laboratory, Catalan Institute of Oncology, L'Hospitalet de Llobregat, Barcelona, Spain Virus and Cancer Laboratory. Bellvitge Institute of Biomedical Research (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Félez-Sánchez
authors.affiliation: Molecular Bioinformatics, Institute of Computer Science, Johann Wolfgang Goethe University, Frankfurt am Main, Germany Paul-Ehrlich-Institut, Federal Institute for Vaccines and Biomedicines, Langen, Germany.
authors.forename: Jan-Hendrik
authors.initials: JH
authors.lastname: Trösemeier
authors.affiliation: Infections and Cancer Laboratory, Catalan Institute of Oncology, L'Hospitalet de Llobregat, Barcelona, Spain Virus and Cancer Laboratory. Bellvitge Institute of Biomedical Research (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain Département d'Ecologie Evolutive Centre d'Ecologie Fonctionnelle et Evolutive, CNRS - UMR 5175, Montpellier, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Bedhomme
authors.affiliation: Facultad de Economía y Empresa, University Salamanca, Salamanca, Spain.
authors.forename: Maria Isabel
authors.initials: MI
authors.lastname: González-Bravo
authors.affiliation: Paul-Ehrlich-Institut, Federal Institute for Vaccines and Biomedicines, Langen, Germany.
authors.forename: Christel
authors.initials: C
authors.lastname: Kamp
authors.affiliation: Infections and Cancer Laboratory, Catalan Institute of Oncology, L'Hospitalet de Llobregat, Barcelona, Spain Virus and Cancer Laboratory. Bellvitge Institute of Biomedical Research (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain igbravo@iconcologia.net.
authors.forename: Ignacio G
authors.initials: IG
authors.lastname: Bravo
mesh_terms: D001482:Base Composition; D036022:Capsid Proteins / Q000235:genetics; D003062:Codon; D004279:DNA, Viral / Q000737:chemistry; D019143:Evolution, Molecular; D015870:Gene Expression; D005814:Genes, Viral; D006801:Humans; D009369:Neoplasms / Q000821:virology; D009856:Oncogene Proteins, Viral / Q000235:genetics; D027383:Papillomaviridae / Q000235:genetics*; D030361:Papillomavirus Infections / Q000175:diagnosis / Q000821:virology*; D014860:Warts / Q000821:virology
chemical_list: D036022:Capsid Proteins; D003062:Codon; D004279:DNA, Viral; D009856:Oncogene Proteins, Viral
keywords: acute infection; cancer; chronic infection; clinical presentation; codon usage preferences; genotype–phenotype; human viruses; immune system; mutation; translational selection; warts