Genetic diversity of hepatitis D virus genotype‐1 in Europe allows classification into subtypes

Abstract

Summary Hepatitis delta virus (HDV) is an RNA virus which leads to both acute and chronic forms of hepatitis. At present, HDV isolates have been classified into eight major genotypes distributed over different geographical regions. Recent increase in HDV sequences in Europe and worldwide has enabled us to revisit the taxonomic classification of HDV. A total of 116 large hepatitis delta antigen (L‐HDAg) nucleotide sequences and 13 full‐length HDV genome sequences belonging to genotype‐1 from our European cohort, as well as 621 L‐HDAg nucleotide sequences belonging to genotype‐1 to genotype‐8 retrieved from the GenBank NCBI were included in this study. All 116 isolates of our cohort and 341 of 621 isolates (60%) account for genotype‐1, while the remaining 40% of isolates were unevenly distributed across genotype‐2 to genotype‐8. Phylogenetic analysis of 98 L‐HDAg sequences selected after elimination of redundant sequences of all 737 isolates was performed to identify plausible subtypes within HDV genotype‐1. Pairwise genetic distances for L‐HDAg sequences were calculated to estimate the inter‐genotype and inter‐subtype differences. The HDV genotype‐1 isolates phylogenetically formed five distinct clusters (genotype 1a‐1e), each of them corresponding to a distinct geographic region. Two distinct subtypes for HDV genotype‐2 and ‐4 (ie ‐2a and ‐2b; ‐4a and ‐4b, respectively) could be identified based on isolate sequences from GenBank. The previously defined genotype‐1 to genotype‐8 have an inter‐genotypic difference of ≥10%, while the newly defined subtypes of genotype‐1, ‐2 and ‐4 show an inter‐subtype difference of ≥3% to <10% from the average diversity. In addition, we identified unique amino acid residues, known as specificity‐determining positions, amongst the proposed subtypes.

Global Distribution of Hepatitis D Virus Genotypes: A Systematic Review

“…These two recent studies are important since they reported the introduction of new viral strains to Europe by immigration as previously discussed (88,89). In the Middle East, mainly HDV I was isolated from patients with HDV infection (26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)78). Studies from Turkey (34)(35)(36)(37)(38)(39) and Israel (78) exclusively detected HDV I.…”

“…In European countries, HDV I, II, and African genotypes were detected in patients with HDV infection (11, 33, 45-47, 66, 69-71, 77, 82). In detail, in Albania (71), Germany (33,66), Greece (71), Italy (33,(45)(46)(47), Romania (47,69), and Spain (33,70), only HDV I was isolated. In the study by Ivaniushina et al (82) in Russia, in addition to HDV I, HDV II was observed, which is justified with the fact that the study was conducted in Yakutia located in the east of Russia, a region near the Chinese borders.…”

“…Data extraction of the 71 studies identified 77 records (based on the geographical location of sampling) in 33 countries. The sampling locations were Brazil (17-25) with nine records, Iran (26-33) with eight records, Turkey (34)(35)(36)(37)(38)(39) and Taiwan (12,(40)(41)(42)(43)(44) each with six records, Italy (33,(45)(46)(47) and Pakistan (48-51) each with four records,…”

Human hepatitis D virus-specific T cell epitopes

“…Heterogeneity and viral evolution HDV shows great genetic variance, a broad range of viral quasispecies exist within the same infected individual 5 . The intragenotypic genetic variability of HDV genotype 1 is estimated at 11.3-14.3% 36 , and recently, a subclassification of genotypes has been proposed 37 .…”

“… 5 The intragenotypic genetic variability of HDV genotype 1 is estimated to be 11.3–14.3% 36 and, recently, a subclassification of genotypes was proposed. 37 …”