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HBV genotypes E and A deletions and recombination: two sides of the same coin?

HBV genotypes E and A deletions and recombination: two sides of the same coin? Penelope Garmiri 1 , Andre Loua 2 , Daniel Candotti 3 and Jean-Pierre Allain 1 1 Dept of Haematology, University of Cambridge 2 National Blood Transfusion Centre, Conakry, Guinea 3 NHSBT, Cambridge.

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HBV genotypes E and A deletions and recombination: two sides of the same coin?

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  1. HBV genotypes E and A deletions and recombination: two sides of the same coin? Penelope Garmiri1, Andre Loua2, Daniel Candotti3 and Jean-Pierre Allain1 1 Dept of Haematology, University of Cambridge 2National Blood Transfusion Centre, Conakry, Guinea 3NHSBT, Cambridge

  2. HBV prevalence in Guinea, West Africa • HBV genotype E became prevalent in West Africa over the past 300 years • HBsAg carriage ranging between 12% and 25% is the highest in the world • In Guinea, the prevalence of HBsAg+ in 1st time blood donors is 15% • Very high HBV exposure in population (75%)

  3. 100 AY090454 Nicaragua H AY090457 Nicaragua H X69798 Brazil F 100 X75658 France F X75663 Colombia F AB036910 Venezuela F AB036920 Venezuela F 100 M54923 Indonesia B D23678 Japan B D50522 Japan B D50519 Japan C 100 M38636 Korea C D23680 Japan C AB194949 Cameroon A3 GU1616* 100 GU1607* GH2537 Ghana* AM180623 Mali A4 100 GU1021^ AY934764 Gambia A3 AB194952 Cameroon A3 AB194951 Cameroon A3 84 A3 AM180624 Cameroon A3 AB194950 Cameroon A3 AM184126 Gabon A3 AM184125 Gabon A3 AY934763 Gambia A3 100 AF297624 South Africa A2 A2 AF143302 A2 DQ788725 Germany A2 AB116078 USA A2 EF208113 Germany A2 DQ020002 Congo A1 AY934772 Uganda A1 AY934773 Tanzania A1 100 AM494718 Cent African Republ A1 AY934766 Somalia A1 A1 AY934765 Somalia A1 AB246336 South Africa A1 AY934771 Somalia A1 AY903452 South Africa A1 AY934767 Somalia A1 AY934768 Somalia A1 AY934769 Somalia A1 AY934770 Somalia A1 100 AB056515 USA G AB056513 USA G AB064311 USA G GH16 Ghana* 98 AB033558 Japan D5 AB048703 Australia D4 100 AY233291 S. Africa D3 X80925 Greece D2 Z35716 Poland D AB104710 Egypt D1 X02496 Latvia D GU754* GU763* AB091256 Cote Ivoire E 98 100 E AB106564 Ghana E X75657 France E X75664 Senegal E AB091255 Cote Ivoire E  77 Guinea E^ 0.1 Phylogenetic analysis of full genome sequences from Guinea • 81 full genome sequences • Genotype A3 : 1 seq • Genotype E : 77 seq • Seq in blue: Recombinants

  4. A EcoRI 3222 bp Wild type 2241 1979 1  262 bp 2007 2314 2  49 bp 147 bp 2010 2235 4  37 bp 78 bp 1818 2454 Core Pre-core B 7 Guinean strains with deletions in the core region

  5. Recombinant strains • Indication • Differential clustering of sequences during assembling • Unusual clustering of samples during phylogenetic analysis • Confirmation • NCBI/ Genotyping function • SIMPLOT software

  6. Guinean recombinant strains • GU1616, GU754, GU763: full genome • GU1125, GU1127, GU1607: partial sequences • GH16, GH2537: full genome from Ghana • Further confirmation - Cloning

  7. Evidence of recombination between HBV genotype E and A and E and D in strains originating from Guinea and Ghana Red: genotype A Blue: genotype E Orange: genotype D

  8. Schematic representation of Guinean and Ghanaian HBV A/E and E/D recombinant strains

  9. Schematic representation of clone diversity from a single plasma sample from Ghana (GH99)

  10. SIMPLOT analysis of GU1127 recombinant clones

  11. SIMPLOT analysis of GU1607 recombinant clones

  12. SIMPLOT analysis of GU1616 recombinant clones

  13. Overview of the recombination and deletion points in West African strains Deletions and recombinations occur in similar core regions suggesting preferential DNA re-arrangement in this area of HBV genome

  14. Viral Load distribution of HBsAg+ Guinean samples

  15. Origin & epidemiology of Rec HBV in Guinea The ratio E/A3 is 77/1 but 7% of donors carry recombinant forms (RFs) Recombination points are identical in multiple strains - Recombination occurs in the same positions of the HBV genome and/or - RFs are infectious (CRFs) It most likely happened earlier when the balance of E and A genotypes in the population was different Viral Load of Rec samples is similarly distributed to the WT samples

  16. Summary • Genotype E is most prevalent in Guinea (93.9%) • Core deletions in Guinea strains (8.5%); evidence of multiple populations • Recombination events between genotypes E and A are frequent in Guinea (7.1%) • Several E/A infectious recombinant forms might be circulating in the region • Deletions and recombinations occur in the core region suggesting preferential DNA rearrangement in this area of HBV genome

  17. Acknowledgements • The staff of National Blood Transfusion Centre, Conakry for collecting and testing the donor samples • Dr I.H.A. Barnes for determining the HBV BCP/PC sequences of the strains included in this study • Dr B. Meldal for her input in the phylogenetic analysis • Funding from National Health Service Blood and Transplant (NHSBT)

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