title: Epidemiological history and genomic characterization of non-D1 HBV strains identified in Iran.
abstract: BACKGROUND
  Hepatitis B virus (HBV) has been classified into eight genotypes and forty subgenotypes. Genotype D of HBV is the most worldwide distributed genotype and HBV subgenotype D1 has been isolated from Iranian patients.
  
  
  OBJECTIVE
  To characterize for the first time complete genomes of recently emerged non-D1 strains in Iran.
  
  
  METHODS
  HBV complete genomes isolated from 9 Iranian HBV carriers were sequenced. Different diversities of the ORFs were mapped and evolutionary history relationships were investigated.
  
  
  RESULTS
  Phylogenetic analysis identified four D2 subgenotypes and five D3 subgenotypes of HBV in the studied patients. Of note, D2 strains clustered with strains from Lebanon and Syria. The time of the most recent common ancestor (TMRCA) of the first cluster of D2 was dated at 1953 (BCI=1926, 1976) while the second cluster was dated at 1947 (BCI=1911, 1978). All five Iranian D3 strains formed a monophyletic cluster with Indian strain and dated back to 1967 (BCI=1946, 1987). Surprisingly, two D3 strains had an adw2 subtype. Interestingly, more than 80% of the present strains showed precore mutations, while two isolates carried basal core promoter variation.
  
  
  CONCLUSIONS
  Iranian D2 and D3 isolates were introduced on at least two and one occasion in Iran and diverged from west and south Asian HBV strains, respectively. Considering the impact of the different (sub) genotypes on clinical outcome, exploring the distinct mutational patterns of Iranian D1 and non-D1 strains is of clinical importance.
authors.affiliation: Department of Microbiology and Immunology, Laboratory of Clinical and Epidemiological Virology, Rega Institute for Medical Research, KU Leuven, Leuven, Belgium; Molecular Biology and Immunology Department, Fundación Instituto de Inmunología de Colombia (FIDIC), Bogotá, Colombia; Basic Sciences Department, School of Medicine and Health Sciences, Universidad del Rosario, Bogotá, Colombia; Centro de Malária e Outras Doenc¸ as Tropicais and Unidade de Saúde Pública Internacional e Bioestatística, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, Lisbon, Portugal.
authors.forename: Andrea-Clemencia
authors.initials: AC
authors.lastname: Pineda-Peña
authors.affiliation: Department of Zoology, University of Oxford, South Parks Road, OX1-3PS, Oxford, United Kingdom.
authors.forename: Nuno Rodrigues
authors.initials: NR
authors.lastname: Faria
authors.affiliation: Department of Microbiology and Immunology, Laboratory of Clinical and Epidemiological Virology, Rega Institute for Medical Research, KU Leuven, Leuven, Belgium.
authors.forename: Thomas
authors.initials: T
authors.lastname: Mina
authors.affiliation: Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Harlyne J. Norris Cancer Research Tower, Los Angeles, CA 90033, USA.
authors.forename: Samad
authors.initials: S
authors.lastname: Amini-Bavil-Olyaee
authors.affiliation: Middle East Liver Disease Clinics, Sepahbod Gharani Ave, 14155-3651 Tehran, Iran.
authors.forename: Seyed Moayed
authors.initials: SM
authors.lastname: Alavian
authors.affiliation: Department of Microbiology and Immunology, Laboratory of Clinical and Epidemiological Virology, Rega Institute for Medical Research, KU Leuven, Leuven, Belgium.
authors.forename: Philippe
authors.initials: P
authors.lastname: Lemey
authors.affiliation: Department of Microbiology and Immunology, Laboratory of Clinical and Epidemiological Virology, Rega Institute for Medical Research, KU Leuven, Leuven, Belgium.
authors.forename: Piet
authors.initials: P
authors.lastname: Maes
authors.affiliation: Department of Microbiology and Immunology, Laboratory of Clinical and Epidemiological Virology, Rega Institute for Medical Research, KU Leuven, Leuven, Belgium.
authors.forename: Marc
authors.initials: M
authors.lastname: Van Ranst
authors.affiliation: Department of Microbiology and Immunology, Laboratory of Clinical and Epidemiological Virology, Rega Institute for Medical Research, KU Leuven, Leuven, Belgium; Blood Transfusion Research Centre, High Institute for Research and Education in Transfusion Medicine, Hemmat Exp. Way, 14665-1157, Tehran, Iran. Electronic address: mahmoudreza.pourkarim@uzleuven.be.
authors.forename: Mahmoud Reza
authors.initials: MR
authors.lastname: Pourkarim
mesh_terms: D000328:Adult; D002353:Carrier State / Q000453:epidemiology / Q000821:virology; D016000:Cluster Analysis; D004279:DNA, Viral / Q000737:chemistry / Q000235:genetics; D019143:Evolution, Molecular; D005260:Female; D014644:Genetic Variation; D016679:Genome, Viral; D005838:Genotype; D006509:Hepatitis B / Q000453:epidemiology* / Q000821:virology; D006515:Hepatitis B virus / Q000145:classification* / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D007492:Iran / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D017720:Molecular Epidemiology; D008969:Molecular Sequence Data; D010802:Phylogeny; D017422:Sequence Analysis, DNA; D017385:Sequence Homology
chemical_list: D004279:DNA, Viral
keywords: Ancestor; D2; D3; Evolution; Hepatitis B virus; Iran; Mutation