Deletions and recombinations in the core region of hepatitis B virus genotype E strains from asymptomatic blood donors in Guinea, west Africa

Abstract

The prevalence of hepatitis B virus (HBV) surface antigen (HBsAg) chronic carriage in west Africa is the highest in the world, but its molecular epidemiology remains relatively poorly investigated. Plasma samples from random asymptomatic carriers of HBsAg in Conakry, Guinea, were studied and the complete genome sequences of 81 strains were obtained. Three additional samples from Kumasi, Ghana, were also included in the analysis. Phylogenetic analyses confirmed the dominance of genotype E (95.1 %), including 8.6 % of strains (viral load, 5¾10 3 -2.6¾10 8 IU ml "1 ) comprising dominant variants with large deletions in the core region and minority wild-type variants. The presence of two different patterns of deletions in two and four donors suggested targeted genome fragility between nt 1979 and 2314. The remaining sequences included one subgenotype A3 (1 %) and six A/E recombinant forms (4-7 %). A/E strains with identical points of recombination in three donors suggested strongly that these recombinant HBV strains are circulating and transmitted in the population. Recombination points were concentrated in the core gene. The detection of similar A/E recombinant strains in Ghana suggested a geographical extension of recombinant HBV to the region. The quasispecies of one additional Ghanaian strain sequenced in the pre-surface/surface region resolved into dominant clones of either the A or E genotype, but also three different patterns of A/E recombinant variants. The observation that both deletions of genotype E strains and A/E recombination points are mostly located in the core gene at specific positions indicates a region of the genome where genetic rearrangements preferentially take place.

A novel hepatitis B virus (HBV) subgenotype D (D8) strain, resulting from recombination between genotypes D and E, is circulating in Niger along with HBV/E strains

“…Elsewhere in Africa, several hybrid strains have been described as involving HBV/E and genotypes A, D and G (Bekondi et al, 2007;Garmiri et al, 2009;Kurbanov et al, 2005;Laoi & Crowley, 2008;Meldal et al, 2009;Mulders et al, 2004;Olinger et al, 2006). Molecular analyses often found these same recombinant sites.…”

“…Interestingly, Niger is located between the Maghreb (Algeria in the north) where HBV/D strains are dominant (Ayed et al, 2007;Bahri et al, 2006;Ezzikouri et al, 2008;Khelifa & Thibault, 2009;Meldal et al, 2009) and tropical sub-Saharan west Africa where HBV/E is prevalent (Andernach et al, 2009;Garmiri et al, 2009;Hubschen et al, 2008). Moreover, Niger is also historically a pastoral nomad society, with records of several population migrations, which may well account for the spread of HBV strains of different genotypes in the Nigerian population, leading to the emergence of recombinant strains.…”

“…For example, a recombinant between HBV/C and HBV/D is the dominant subgenotype circulating in Tibet (Cui et al, 2002). In Africa, such recombination events have also been described, including recombinants A-D (Owiredu et al, 2001), A-E (Garmiri et al, 2009;Kurbanov et al, 2005), D-E-A and the G insertion (Olinger et al, 2006). Very recently, new HBV/ D-E recombinants were identified in the Central African Republic, Ireland (in a west African patient), Tunisia and Guinea, with all of them sharing the same recombination profile (Bekondi et al, 2007;Garmiri et al, 2009;Laoi & Crowley, 2008;Meldal et al, 2009).…”

“…In Africa, such recombination events have also been described, including recombinants A-D (Owiredu et al, 2001), A-E (Garmiri et al, 2009;Kurbanov et al, 2005), D-E-A and the G insertion (Olinger et al, 2006). Very recently, new HBV/ D-E recombinants were identified in the Central African Republic, Ireland (in a west African patient), Tunisia and Guinea, with all of them sharing the same recombination profile (Bekondi et al, 2007;Garmiri et al, 2009;Laoi & Crowley, 2008;Meldal et al, 2009). Interestingly, Niger is situated in the Sahara region, between the Maghreb (Algeria, Morocco and Tunisia) in the north, where HBV/D is predominant (Khelifa & Thibault, 2009), and Mali, Burkina Faso, Benin and Nigeria in the west and south, where HBV/E is predominant (Hubschen et al, 2008;Kramvis & Kew, 2007).…”

Identification of novel recombinants of hepatitis B virus genotypes F and G in human immunodeficiency virus-positive patients from Argentina and Brazil

“…Dual HBV infection and genomic recombination between different genotypes have been increasingly documented (Simmonds & Midgley, 2005;Sugauchi et al, 2003;Yang et al, 2007). Recombination has been found to occur more frequently in certain 'hot-spot' regions of the viral genome, such as the core region (Bowyer & Sim, 2000;Garmiri et al, 2009;Luo et al, 2004), pre-S1 (Chen et al, 2004), pre-S2/S (Chen et al, 2006;Wang et al, 2005), polymerase (Kurbanov et al, 2005;Magiorkinis et al, 2005) and X (Martin et al, 2011), and has been considered a significant source of HBV genetic variability (Simmonds & Midgley, 2005). In our study, all but one G/F recombinant clones had recombination breakpoints in the core region ( Fig.…”