title: Global Genomic Diversity of Human Papillomavirus 11 Based on 433 Isolates and 78 Complete Genome Sequences.
abstract: Human papillomavirus 11 (HPV11) is an etiological agent of anogenital warts and laryngeal papillomas and is included in the 4-valent and 9-valent prophylactic HPV vaccines. We established the largest collection of globally circulating HPV11 isolates to date and examined the genomic diversity of 433 isolates and 78 complete genomes (CGs) from six continents. The genomic variation within the 2,800-bp E5a-E5b-L1-upstream regulatory region was initially studied in 181/207 (87.4%) HPV11 isolates collected for this study. Of these, the CGs of 30 HPV11 variants containing unique single nucleotide polymorphisms (SNPs), indels (insertions or deletions), or amino acid changes were fully sequenced. A maximum likelihood tree based on the global alignment of 78 HPV11 CGs (30 CGs from our study and 48 CGs from GenBank) revealed two HPV11 lineages (lineages A and B) and four sublineages (sublineages A1, A2, A3, and A4). HPV11 (sub)lineage-specific SNPs within the CG were identified, as well as the 208-bp representative region for CG-based phylogenetic clustering within the partial E2 open reading frame and noncoding region 2. Globally, sublineage A2 was the most prevalent, followed by sublineages A1, A3, and A4 and lineage B.
  
  
  
  This collaborative international study defined the global heterogeneity of HPV11 and established the largest collection of globally circulating HPV11 genomic variants to date. Thirty novel complete HPV11 genomes were determined and submitted to the available sequence repositories. Global phylogenetic analysis revealed two HPV11 variant lineages and four sublineages. The HPV11 (sub)lineage-specific SNPs and the representative region identified within the partial genomic region E2/noncoding region 2 (NCR2) will enable the simpler identification and comparison of HPV11 variants worldwide. This study provides an important knowledge base for HPV11 for future studies in HPV epidemiology, evolution, pathogenicity, prevention, and molecular assay development.
authors.affiliation: Institute of Pathology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
authors.forename: Mateja M
authors.initials: MM
authors.lastname: Jelen
authors.affiliation: Department of Microbiology, Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China.
authors.forename: Zigui
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
authors.forename: Boštjan J
authors.initials: BJ
authors.lastname: Kocjan
authors.affiliation: Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
authors.forename: Lea
authors.initials: L
authors.lastname: Hošnjak
authors.affiliation: Department of Medical Microbiology and Virology, Faculty of Health Sciences, University of the Free State, Bloemfontein, South Africa.
authors.forename: Felicity J
authors.initials: FJ
authors.lastname: Burt
authors.affiliation: Department of Microbiology, Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China.
authors.forename: Paul K S
authors.initials: PKS
authors.lastname: Chan
authors.affiliation: Human Virology Group, National Council of Scientific and Technical Research, Institute of Molecular and Cell Biology of Rosario, Rosario, Argentina.
authors.forename: Diego
authors.initials: D
authors.lastname: Chouhy
authors.affiliation: Department of Medical Microbiology and Virology, Faculty of Health Sciences, University of the Free State, Bloemfontein, South Africa.
authors.forename: Catharina E
authors.initials: CE
authors.lastname: Combrinck
authors.affiliation: Institute of Microbiology, Lausanne University Hospital (CHUV), and University of Lausanne, Lausanne, Switzerland.
authors.forename: Christine
authors.initials: C
authors.lastname: Estrade
authors.affiliation: Department of Obstetrics and Gynaecology, Cardiff University School of Medicine, Institute of Cancer and Genetics, Cardiff, United Kingdom.
authors.forename: Alison
authors.initials: A
authors.lastname: Fiander
authors.affiliation: Department of Microbiology and Infectious Diseases, The Royal Women's Hospital, Parkville, Victoria, Australia.|Department of Obstetrics and Gynaecology, University of Melbourne, Melbourne, Victoria, Australia.|Murdoch Childrens Research Institute, Parkville, Victoria, Australia.
authors.forename: Suzanne M
authors.initials: SM
authors.lastname: Garland
authors.affiliation: Human Virology Group, National Council of Scientific and Technical Research, Institute of Molecular and Cell Biology of Rosario, Rosario, Argentina.
authors.forename: Adriana A
authors.initials: AA
authors.lastname: Giri
authors.affiliation: Oncogenic Viruses Service, National Institute of Infectious Diseases-ANLIS Dr. Carlos G. Malbrán, Buenos Aires, Argentina.
authors.forename: Joaquín Víctor
authors.initials: JV
authors.lastname: González
authors.affiliation: Medizinisches Versorgungszentrum wagnerstibbe für Laboratoriumsmedizin und Pathologie GmbH, Hannover, Germany.
authors.forename: Arndt
authors.initials: A
authors.lastname: Gröning
authors.affiliation: Department of Obstetrics and Gynaecology, Cardiff University School of Medicine, Institute of Cancer and Genetics, Cardiff, United Kingdom.
authors.forename: Sam
authors.initials: S
authors.lastname: Hibbitts
authors.affiliation: Dermatology Research Centre, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China.|Department of Health, Social Hygiene Service, Centre for Health Protection, Hong Kong Special Administrative Region, China.
authors.forename: Tommy N M
authors.initials: TNM
authors.lastname: Luk
authors.affiliation: Histocompatibility and Molecular Genetics Laboratory, Dr. Julio C. Perrando Hospital, Resistencia, Chaco, Argentina.
authors.forename: Karina
authors.initials: K
authors.lastname: Marinic
authors.affiliation: Momate Memorial Laboratory, Tokyo, Japan.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Matsukura
authors.affiliation: Medizinisches Versorgungszentrum wagnerstibbe für Laboratoriumsmedizin und Pathologie GmbH, Hannover, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Neumann
authors.affiliation: Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
authors.forename: Anja
authors.initials: A
authors.lastname: Oštrbenk
authors.affiliation: Oncogenic Viruses Service, National Institute of Infectious Diseases-ANLIS Dr. Carlos G. Malbrán, Buenos Aires, Argentina.
authors.forename: Maria Alejandra
authors.initials: MA
authors.lastname: Picconi
authors.affiliation: Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
authors.forename: Martin
authors.initials: M
authors.lastname: Sagadin
authors.affiliation: Institute of Microbiology, Lausanne University Hospital (CHUV), and University of Lausanne, Lausanne, Switzerland.
authors.forename: Roland
authors.initials: R
authors.lastname: Sahli
authors.affiliation: Department of Otorhinolaryngology, Faculty of Health Sciences, University of the Free State, Bloemfontein, South Africa.
authors.forename: Riaz Y
authors.initials: RY
authors.lastname: Seedat
authors.affiliation: Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
authors.forename: Katja
authors.initials: K
authors.lastname: Seme
authors.affiliation: Viral Exanthemata and STD Section, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada.
authors.forename: Alberto
authors.initials: A
authors.lastname: Severini
authors.affiliation: Histocompatibility and Molecular Genetics Laboratory, Dr. Julio C. Perrando Hospital, Resistencia, Chaco, Argentina.
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Sinchi
authors.affiliation: Department of Experimental Virology, National Reference Laboratory for Papillomaviruses, Institute of Hematology and Blood Transfusion, Prague, Czech Republic.
authors.forename: Jana
authors.initials: J
authors.lastname: Smahelova
authors.affiliation: Department of Microbiology and Infectious Diseases, The Royal Women's Hospital, Parkville, Victoria, Australia.|Department of Obstetrics and Gynaecology, University of Melbourne, Melbourne, Victoria, Australia.|Murdoch Childrens Research Institute, Parkville, Victoria, Australia.
authors.forename: Sepehr N
authors.initials: SN
authors.lastname: Tabrizi
authors.affiliation: Department of Experimental Virology, National Reference Laboratory for Papillomaviruses, Institute of Hematology and Blood Transfusion, Prague, Czech Republic.
authors.forename: Ruth
authors.initials: R
authors.lastname: Tachezy
authors.affiliation: Viral Exanthemata and STD Section, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada.
authors.forename: Sarah
authors.initials: S
authors.lastname: Tohme Faybush
authors.affiliation: Department of Otolaryngology, Lithuanian University of Health Sciences, Medical Academy, Kaunas, Lithuania.
authors.forename: Virgilijus
authors.initials: V
authors.lastname: Uloza
authors.affiliation: Department of Otolaryngology, Lithuanian University of Health Sciences, Medical Academy, Kaunas, Lithuania.
authors.forename: Ingrida
authors.initials: I
authors.lastname: Uloziene
authors.affiliation: DNA Laboratories Sdn. Bhd., UKM-MTDC Technology Centre, Universiti Kebangsaan Malaysia, Bangi, Malaysia.
authors.forename: Yong Wee
authors.initials: YW
authors.lastname: Wong
authors.affiliation: Department of Molecular Diagnostics, University Hospital for Infectious Diseases Dr. Fran Mihaljević, Zagreb, Croatia.
authors.forename: Snježana
authors.initials: S
authors.lastname: Židovec Lepej
authors.affiliation: Departments of Pediatrics, Microbiology and Immunology, Epidemiology and Population Health, Obstetrics and Gynecology, and Women's Health, Albert Einstein College of Medicine, New York, New York, USA.
authors.forename: Robert D
authors.initials: RD
authors.lastname: Burk
authors.affiliation: Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia mario.poljak@mf.uni-lj.si.
authors.forename: Mario
authors.initials: M
authors.lastname: Poljak
mesh_terms: D019143:Evolution, Molecular; D014644:Genetic Variation; D016679:Genome, Viral; D023281:Genomics; D005838:Genotype; D059014:High-Throughput Nucleotide Sequencing; D052140:Human papillomavirus 11 / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D016013:Likelihood Functions; D016366:Open Reading Frames; D030361:Papillomavirus Infections / Q000821:virology*; D010802:Phylogeny; D020641:Polymorphism, Single Nucleotide; D016415:Sequence Alignment