The Hepatitis B Virus Genotypes E to J: The Overlooked Genotypes

Abstract

Hepatitis B virus (HBV) genotypes E to J are understudied genotypes. Genotype E is found almost exclusively in West Africa. Genotypes F and H are found in America and are rare in other parts of the world. The distribution of genotype G is not completely known. Genotypes I and J are found in Asia and probably result from recombination events with other genotypes. The number of reported sequences for HBV genotypes E to J is small compared to other genotypes, which could impact phylogenetic and pairwise distance analyses. Genotype F is the most divergent of the HBV genotypes and is subdivided into six subgenotypes F1 to F6. Genotype E may be a recent genotype circulating almost exclusively in sub-Saharan Africa. Genotype J is a putative genotype originating from a single Japanese patient. The paucity of data from sub-Saharan Africa and Latin America is due to the under-representation of these regions in clinical and research cohorts. The purpose of this review is to highlight the need for further research on HBV genotypes E to J, which appear to be overlooked genotypes.

Keywords: Africa; Asia; Latin America; genotype E; genotype F; genotype G; genotype H; genotype I; genotype J; hepatitis B virus.

Figure 1

Maps of hepatitis B virus (HBV) whole-genome sequence distribution worldwide; (a) genotype E sequences, (b) genotype F sequences, (c) genotype G sequences, and (d) genotype H sequences. All available full-length sequences for HBV genotypes E to H were downloaded from GenBank and HBV database (HBVdb). The number of complete genome sequences of genotypes E, F, G, and H included in the map analysis (including recombinants) after removal of redundant sequences was 332, 339, 59, and 36, respectively. HBV genotype E has also been found in Afro-descendant populations in Colombia [13], but no complete genome is available.

Figure 2

Phylogenetic analysis of HBV genotype E sequences. The evolutionary history was inferred by using the Maximum Likelihood (ML) method and General Time Reversible (GTR) model. The tree with the highest log likelihood is shown. The percentage of trees in which the associated taxa clustered together is shown next to the branches. Initial tree(s) for the heuristic search were obtained automatically by applying Neighbor-Join and BioNJ algorithms to a matrix of pairwise distances estimated using the Maximum Composite Likelihood (MCL) approach and then selecting the topology with the superior log likelihood value. A discrete Gamma distribution was used to model evolutionary rate differences among sites (3 categories). The rate variation model allowed for some sites to be evolutionary. The tree is drawn to scale, with branch lengths measured in the number of substitutions per site. This analysis involved 307 non-redundant nucleotide sequences out of the 326 sequences initially included (19 identical sequences had to be omitted). Codon positions included were 1st + 2nd + 3rd + Noncoding. Evolutionary analyses were conducted in Molecular Evolutionary Genetics Analysis (MEGA) version 11 [24]. Recombinant sequences were identified using the jumping profile Hidden Markov Model (jpHMM) tool [25] and were not included in the phylogenetic analysis, as for identical sequences. All the sequences are included in Supplemental Table S1.

Figure 3

Phylogenetic analysis of HBV genotype F. The evolutionary history was inferred by using the ML method and GTR model. The tree with the highest log likelihood is shown. The percentage of trees in which the associated taxa clustered together is shown next to the branches. Initial tree(s) for the heuristic search were obtained automatically by applying Neighbor-Join and BioNJ algorithms to a matrix of pairwise distances estimated using the MCL approach and then selecting the topology with the superior log likelihood value. A discrete Gamma distribution was used to model evolutionary rate differences among sites (3 categories). The rate variation model allowed for some sites to be evolutionary. The tree is drawn to scale, with branch lengths measured in the number of substitutions per site. This analysis involved 268 non-redundant nucleotide sequences out of the 354 initially included (identical sequences had to be omitted). Codon positions included were 1st + 2nd + 3rd + Noncoding. Evolutionary analyses were conducted in MEGA 11 [24]. Recombinant sequences were identified using the jpHMM tool [25] and were not included in the phylogenetic analysis, as for identical sequences. All the sequences are included in Supplemental Table S2.

Figure 4

Phylogenetic analysis of HBV genotype H. The evolutionary history was inferred by using the ML method and GTR model. The tree with the highest log likelihood is shown. The percentage of trees in which the associated taxa clustered together is shown next to the branches. Initial tree(s) for the heuristic search were obtained automatically by applying Neighbor-Join and BioNJ algorithms to a matrix of pairwise distances estimated using the MCL approach and then selecting the topology with the superior log likelihood value. A discrete Gamma distribution was used to model evolutionary rate differences among sites (3 categories). The rate variation model allowed for some sites to be evolutionary. The tree is drawn to scale, with branch lengths measured in the number of substitutions per site. This analysis involved 39 nucleotide sequences. Codon positions included were 1st + 2nd + 3rd + Noncoding. Evolutionary analyses were conducted in MEGA 11 [24]. Recombinant sequences were identified using the jpHMM tool [25] and were not included in the phylogenetic analysis, as for identical sequences. All the sequences are included in Supplemental Table S3.

Figure 5

Phylogenetic analysis of HBV genotype G. The evolutionary history was inferred by using the ML method and GTR model. The tree with the highest log likelihood is shown. The percentage of trees in which the associated taxa clustered together is shown next to the branches. Initial tree(s) for the heuristic search were obtained automatically by applying Neighbor-Join and BioNJ algorithms to a matrix of pairwise distances estimated using the MCL approach and then selecting the topology with the superior log likelihood value. A discrete Gamma distribution was used to model evolutionary rate differences among sites (3 categories). The rate variation model allowed for some sites to be evolutionary. The tree is drawn to scale, with branch lengths measured in the number of substitutions per site. This analysis involved 35 nucleotide sequences. Codon positions included were 1st + 2nd + 3rd + Noncoding. Evolutionary analyses were conducted in MEGA 11 [24]. Recombinant sequences were identified using the jpHMM tool [25] and were not included in the phylogenetic analysis, as for identical sequences. All the sequences are included in Supplemental Table S4.