title: Virological failure of intralesional cidofovir therapy in recurrent respiratory papillomatosis is not associated with genetic or epigenetic changes of HPV11: complete genome comparison of sequential isolates.
abstract: Five sequential human papillomavirus type 11 (HPV11) positive samples collected from an aggressive juvenile onset recurrent respiratory papillomatosis before, during and after intralesional cidofovir therapy leading to virological failure after initial response were analyzed. Sequencing of the complete genome as well as methylation analysis by bisulfate modification and sequencing of the long control region (LCR) were performed to seek for genetic and epigenetic changes as a possible background for therapy failure. Single-strand conformation polymorphism of E1, E2, E6, E7 and LCR was used to exclude the presence of multiple HPV11 infection. All five complete genomes were identical and all four E2 binding sites in the LCR were uniformly unmethylated in all five genomes. Thus the virological failure was not due to virological factors suggesting that cidofovir action may depend more heavily on the host.
authors.affiliation: Department of Medical Microbiology, University of Debrecen, H-4032 Debrecen, Nagyerdei krt. 98, Hungary. tamasgall@freemail.hu
authors.forename: Tamás
authors.initials: T
authors.lastname: Gáll
authors.forename: Andrea
authors.initials: A
authors.lastname: Kis
authors.forename: Eniko
authors.initials: E
authors.lastname: Fehér
authors.forename: Lajos
authors.initials: L
authors.lastname: Gergely
authors.forename: Krisztina
authors.initials: K
authors.lastname: Szarka
mesh_terms: D000998:Antiviral Agents / Q000008:administration & dosage*; D000077404:Cidofovir; D003596:Cytosine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D019175:DNA Methylation; D004279:DNA, Viral / Q000737:chemistry / Q000235:genetics; D044127:Epigenesis, Genetic; D016679:Genome, Viral; D052140:Human papillomavirus 11 / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D063065:Organophosphonates / Q000008:administration & dosage*; D030361:Papillomavirus Infections / Q000188:drug therapy* / Q000821:virology*; D018807:Polymorphism, Single-Stranded Conformational; D012141:Respiratory Tract Infections / Q000188:drug therapy* / Q000821:virology*; D017422:Sequence Analysis, DNA; D017211:Treatment Failure
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D063065:Organophosphonates; D003596:Cytosine; D000077404:Cidofovir