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Global genomic diversity of human papillomavirus 6 based on 724 isolates and 190 complete genome sequences

Jelen MM 1 , Chen Z 2 , Kocjan BJ 1 , Burt FJ 3 , Chan PK 4 , Chouhy D 5 Show all authors , Combrinck CE 3 , Coutlée F 6 , Estrade C 7 , Ferenczy A 8 , Fiander A 9 , Franco EL 10 , Garland SM 11 , Giri AA 5 , González JV 12 , Gröning A 13 , Heidrich K 13 , Hibbitts S 9 , Hošnjak L 1 , Luk TN 14 , Marinic K 15 , Matsukura T 16 , Neumann A 13 , Oštrbenk A 1 , Picconi MA 12 , Richardson H 17 , Sagadin M 1 , Sahli R 7 , Seedat RY 18 , Seme K 1 , Severini A 19 , Sinchi JL 15 , Smahelova J 20 , Tabrizi SN 11 , Tachezy R 20 , Tohme S 19 , Uloza V 21 , Vitkauskiene A 22 , Wong YW 23 , Zidovec Lepej S 24 , Burk RD 25 , Poljak M 26

Affiliations 

  • 1 Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
  • 2 Department of Pediatrics, Albert Einstein College of Medicine, New York, New York, USA
  • 3 Department of Medical Microbiology and Virology, Faculty of Health Sciences, University of the Free State, Bloemfontein, South Africa
  • 4 Department of Microbiology, Faculty of Medicine, Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China
  • 5 Human Virology Group, National Council of Scientific and Technical Research, Institute of Molecular and Cell Biology of Rosario, Rosario, Argentina
  • 6 Laboratoire de Virologie Moléculaire, Centre de Recherche, Centre Hospitalier de L'Université de Montréal, Hôpital Notre-Dame-Pavillon Deschamps, Montréal, Québec, Canada
  • 7 Lausanne University Hospital (CHUV), Institute of Microbiology, Lausanne, Switzerland
  • 8 Department of Pathology, McGill University and Jewish General Hospital, Montréal, Québec, Canada
  • 9 Department of Obstetrics and Gynaecology, Cardiff University School of Medicine, Institute of Cancer and Genetics, Cardiff, United Kingdom
  • 10 Department of Oncology, Division of Cancer Epidemiology, McGill University, Montréal, Québec, Canada
  • 11 Department of Microbiology and Infectious Diseases, The Royal Women's Hospital, Parkville, Victoria, Australia Department of Obstetrics and Gynaecology, University of Melbourne, Victoria, Australia Murdoch Children's Research Institute, Parkville, Victoria, Australia
  • 12 Oncogenic Viruses Service, National Institute of Infectious Diseases-ANLIS Dr. Carlos G. Malbrán, Buenos Aires, Argentina
  • 13 Medizinisches Versorgungszentrum wagnerstibbe für Laboratoriumsmedizin und Pathologie GmbH, Hannover, Germany
  • 14 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
  • 15 Histocompatibility and Molecular Genetics Laboratory, Dr. Julio C. Perrando Hospital, Resistencia, Chaco, Argentina
  • 16 Ganshintetsu Memorial Laboratory, Department of Virology II, National Institute of Health, Tokyo, Japan
  • 17 Queen's Cancer Research Institute, Queen's University, Kingston, Ontario, Canada
  • 18 Department of Otorhinolaryngology, Faculty of Health Sciences, University of the Free State, Bloemfontein, South Africa
  • 19 Viral Exanthemata and STD Section, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada
  • 20 Department of Experimental Virology, National Reference Laboratory for Papillomaviruses, Institute of Hematology and Blood Transfusion, Prague, Czech Republic
  • 21 Department of Otolaryngology, Lithuanian University of Health Sciences, Medical Academy, Kaunas, Lithuania
  • 22 Department of Laboratory Medicine, Lithuanian University of Health Sciences, Medical Academy, Kaunas, Lithuania
  • 23 DNA Laboratories Sdn. Bhd., UKM-MTDC Technology Centre, Universti Kebangsaan Malaysia, Bangi, Malaysia
  • 24 Department of Molecular Diagnostics, University Hospital for Infectious Diseases Dr. Fran Mihaljević, Zagreb, Croatia
  • 25 Departments of Microbiology and Immunology, Epidemiology and Population Health, Obstetrics and Gynecology and Women's Health, Albert Einstein College of Medicine, New York, New York, USA Department of Pediatrics, Albert Einstein College of Medicine, New York, New York, USA
  • 26 Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia mario.poljak@mf.uni-lj.si
J Virol, 2014 Jul;88(13):7307-16.
PMID: 24741079 DOI: 10.1128/JVI.00621-14

Abstract

Human papillomavirus type 6 (HPV6) is the major etiological agent of anogenital warts and laryngeal papillomas and has been included in both the quadrivalent and nonavalent prophylactic HPV vaccines. This study investigated the global genomic diversity of HPV6, using 724 isolates and 190 complete genomes from six continents, and the association of HPV6 genomic variants with geographical location, anatomical site of infection/disease, and gender. Initially, a 2,800-bp E5a-E5b-L1-LCR fragment was sequenced from 492/530 (92.8%) HPV6-positive samples collected for this study. Among them, 130 exhibited at least one single nucleotide polymorphism (SNP), indel, or amino acid change in the E5a-E5b-L1-LCR fragment and were sequenced in full. A global alignment and maximum likelihood tree of 190 complete HPV6 genomes (130 fully sequenced in this study and 60 obtained from sequence repositories) revealed two variant lineages, A and B, and five B sublineages: B1, B2, B3, B4, and B5. HPV6 (sub)lineage-specific SNPs and a 960-bp representative region for whole-genome-based phylogenetic clustering within the L2 open reading frame were identified. Multivariate logistic regression analysis revealed that lineage B predominated globally. Sublineage B3 was more common in Africa and North and South America, and lineage A was more common in Asia. Sublineages B1 and B3 were associated with anogenital infections, indicating a potential lesion-specific predilection of some HPV6 sublineages. Females had higher odds for infection with sublineage B3 than males. In conclusion, a global HPV6 phylogenetic analysis revealed the existence of two variant lineages and five sublineages, showing some degree of ethnogeographic, gender, and/or disease predilection in their distribution.

IMPORTANCE: This study established the largest database of globally circulating HPV6 genomic variants and contributed a total of 130 new, complete HPV6 genome sequences to available sequence repositories. Two HPV6 variant lineages and five sublineages were identified and showed some degree of association with geographical location, anatomical site of infection/disease, and/or gender. We additionally identified several HPV6 lineage- and sublineage-specific SNPs to facilitate the identification of HPV6 variants and determined a representative region within the L2 gene that is suitable for HPV6 whole-genome-based phylogenetic analysis. This study complements and significantly expands the current knowledge of HPV6 genetic diversity and forms a comprehensive basis for future epidemiological, evolutionary, functional, pathogenicity, vaccination, and molecular assay development studies.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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