title: Phylogeny and polymorphism in the long control region, E6, and L1 of human papillomavirus types 53, 56, and 66 in central Brazil.
abstract: BACKGROUND
  Several studies related that different human papillomavirus (HPV) types and intratype variants can present different oncogenic potential. In opposite to HPVs 16 and 18 variants, information about variants of other carcinogenic HPV types is still scarce. The aim of this study was to investigate the genetic variability of HPVs 53, 56, and 66 from Central Brazil isolates.
  
  
  METHODS
  The long control region (LCR), E6, and L1 genomic regions were amplified and sequenced. We evaluate for nucleotide variations in relation to the reference sequence of each HPV type and also the conservation of physicochemical properties of the deduced amino acid substitutions. In silico analysis was performed to locate binding sites for transcriptional factors within the LCR. Moreover, we performed a phylogenetic analysis with the Central Brazilian and worldwide sequences available at genomic databases.
  
  
  RESULTS
  Gathering LCR, E6, and L1 genomic regions, the highest genetic variability was found among HPV-53 isolates with 52 nucleotide variations, followed by HPVs 56 and 66 with 24 and 16 nucleotide substitutions, respectively. The genetic analysis revealed 11 new molecular variants of all HPV types analyzed, totalizing 31 new nucleotide and 3 new amino acid variations. Eight nonconservative amino acid substitutions were detected, which may indicate a biological and pathogenic diversity among HPV types. Furthermore, 8 nucleotide substitutions were localized at putative binding sites for transcription factors in the LCR with a potential implication on viral oncogene expression. The HPVs 53, 56, and 66 phylogenetic analysis confirmed a dichotomic division only described to HPV subtypes and different from the patterns described for HPVs 16 and 18 variants.
  
  
  CONCLUSIONS
  The high genetic variability observed emphasizes the importance of investigating polymorphisms in types other than HPVs 16 or 18 to better understand the molecular genomic profile of viral infection by different HPV types.
authors.affiliation: Department of Molecular Biology and Plant Virology, University of Stuttgart, Stuttgart, Germany.
authors.forename: Patrícia Soares
authors.initials: PS
authors.lastname: Wyant
authors.forename: Daniela Marreco
authors.initials: DM
authors.lastname: Cerqueira
authors.forename: Daniella Sousa
authors.initials: DS
authors.lastname: Moraes
authors.forename: José Paulo Gagliardi
authors.initials: JP
authors.lastname: Leite
authors.forename: Cláudia Renata Fernandes
authors.initials: CR
authors.lastname: Martins
authors.forename: Marcelo
authors.initials: M
authors.lastname: de Macedo Brígido
authors.forename: Tainá
authors.initials: T
authors.lastname: Raiol
mesh_terms: D052685:Alphapapillomavirus / Q000235:genetics*; D001938:Brazil; D036022:Capsid Proteins / Q000235:genetics*; D005260:Female; D006801:Humans; D009856:Oncogene Proteins, Viral / Q000235:genetics*; D010802:Phylogeny; D011110:Polymorphism, Genetic
chemical_list: D036022:Capsid Proteins; C114580:HPV L1 protein, Human papillomavirus; D009856:Oncogene Proteins, Viral