J Viral Hepat 2016; 1–11 wileyonlinelibrary.com/journal/jvh
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1 © 2016 John Wiley & Sons Ltd
Received: 21 July 2016
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Accepted: 6 October 2016
DOI: 10.1111/jvh.12631
Summary
Hepatts B virus (HBV) is genetcally highly divergent and classifed in ten genotypes
and forty subgenotypes in distnct ethno-geographic populatons worldwide. Ethiopia
is a country with high HBV prevalence; however, litle is known about the genetc vari-
ability of HBV strains that circulate. Here, we characterize the complete genome of 29
HBV strains originatng from fve Ethiopian regions, by 454 deep sequencing and
Sanger sequencing. Phylogenetcally, ten strains were classifed as genotype A1 and
nineteen as genotype D. Fifeen genotype D strains, provisionally named subgenotype
D10, showed a novel distnct cluster supported by high bootstrap value and >4% nu-
cleotde divergence from other known subgenotypes. In additon, the novel D10
strains harboured nine unique amino acid signatures in the surface, polymerase and X
genes. Seventy-two per cent of the genotype D strains had the precore premature
stop codon G1896A. In additon, 63% genotype A and 33% genotype D strains had the
basal core promoter mutatons, A1762T/G1764A. Furthermore, four pre-S deleton
variants and two recombinants were identfed in this study. In conclusion, we ident-
fed a novel HBV subgenotype D10 circulatng in Ethiopia, underlining the high genetc
variability of HBV strains in Africa.
KEYWORDS
Ethiopia, genetc variability, genotype and subgenotypes, hepatts B virus, novel subgenotype D10
1
Department of Viroscience, Erasmus
Medical Center, Roterdam, The Netherlands
2
Natonal blood bank services, Ministry of
Health, Addis Ababa, Ethiopia
3
Artemis One health, Utrecht, The
Netherlands
4
Center for Infecton Medicine and
Zoonoses Research, University of Veterinary
Medicine, Hannover, Germany
5
ViroClinics BioScience BV, Roterdam, The
Netherlands
Correspondence
Bart L. Haagmans, Department of
Viroscience, Erasmus Medical Center,
Roterdam, The Netherlands.
Email: b.haagmans@erasmusmc.nl
Funding informaton
Nufc, Grant/Award Number: CF8605
ORIGINAL ARTICLE
A novel hepatts B virus subgenotype D10 circulatng in
Ethiopia
G. B. Hundie
1
| V. Stalin Raj
1
| D. Gebre Michael
2
| S. D. Pas
1
| M. P. Koopmans
1
|
A. D. M. E. Osterhaus
3,4
| S. L. Smits
5
| B. L. Haagmans
1
1 | INTRODUCTION
Despite advances in preventon, diagnosis and treatment, hepatts B
virus (HBV) infecton remains a major global health problem, especially
in Africa and Asia, where seroprevalence is high.
1
HBV is the prototype
of the family Hepadnaviridae with a partally double-stranded circular
DNA genome of 3.2 kb organized into four overlapping open reading
frames (ORFs: S, for the surface or envelope gene; C, for the core gene;
X, for the regulatory X gene; and P, for the polymerase gene).
2
Because
its polymerase lacks proof-reading actvity and its genomes undergo
frequent recombinaton, HBV exhibits a high degree of genetc het-
erogeneity.
3
To date, ten genotypes, A-J, defned by an intergroup di-
vergence of greater than 7.5% over the entre genome sequence have
been established.
4-8
Moreover, extensive phylogenetc analyses of
HBV genotypes in diferent studies worldwide have identfed several
subgenotypes within genotypes, A (A1-A6), B (B1-B9), C (C1-C16), D
(D1-D9), F (F1-F4) and I (I1-I2), based on full genome divergence of >
4% but < 7.5%.
4,6,9-14
HBV genotypes and subgenotypes difer in clini-
cal and therapeutc outcomes
15,16
and have distnct ethno-geographic
distributon worldwide.
6,17
Numerous studies carried out in diferent African countries have
also unveiled the emergence of a trend in the geographic distribu-
ton of genotypes and subgenotypes. Subgenotype A1 is dominant in
Abbreviatons: BCP, basal core promoter; HBV, hepatts B virus; ORF, open reading frames;
PC, preCore; RDP, recombinaton detecton program.