Relationships within and between genotypes of hepatitis B virus at points across the genome: footprints of recombination in certain isolates

Abstract

Hepatitis B virus (HBV) was partitioned into type, subtype and isolate categories and the average evolutionary distances within and between categories was plotted at each of 54 points along the genome. The graphs showed alternating variable and conserved domains within and between HBV subtypes and revealed that some specimens assigned to different groups are more similar across several contiguous intervals than specimens belonging to the same group. Isolates were screened individually to determine their conformation to type and mosaic structure was identified in 14/65 specimens. Two entire clades (six specimens) of genotype B had a B/C sequence switch in the core gene region, whereas six genotype D specimens showed D/A switching in one or more regions of the genome. Genotype E was not separate from genotype D in the X and C subgenomic regions. The nature and distribution of polymorphic sites in mosaic regions was mapped at both the nucleotide and protein levels and the position of the variant fragments was related to mutational hot spots and linear epitopes of HBV. Mosaic structure was demonstrated statistically in 11 isolates using bootstrap resampling and recombination, rather than random change, appeared to be the mechanism responsible. The sequence between and including the two DR regions was represented in all putative recombinants. The distribution of genetic distances over subgenomic regions showed that substitution rates are not constant among the lineages of HBV in the preS regions. Genotype F is the most diverse group. Only genotypes A, C and F partition consistently into subtypes.

Hepatitis B Virus of Genotype B with or without Recombination with Genotype C over the Precore Region plus the Core Gene

“…HBV strains of certain genotypes in which a part of the open reading frame is replaced by the corresponding part of those of the other genotypes have been reported (2,3). With a small number of recombinant strains available, it is not clear how frequently they occur and influence the evolution and pathogenicity of HBV.…”

Hepatitis B virus taxonomy and hepatitis B virus genotypes

“…A hypothetical mosaicism of the HBV genome has already been proposed by Bowyer and Sim [73] . This work and later works described most HBV genotypes as a modular genome [63] that represents a mixture of small segments coming from many different HBV genotypes.…”

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.…”