Phylogenetic analysis of HDV isolates from HBsAg positive patients in Karachi, Pakistan

Abstract

BackgroundIn spite of a high occurrence of Hepatitis Delta in the province of Sindh in Pakistan, no genetic study of Hepatitis Delta virus (HDV) isolates from this region was carried out. The aim of this study is to analyze the genetic proximity within local HDV strains, and relationship with other clades of HDV, using phylogenetic analysis.ResultsPhylogenetic analysis of nucleotide sequences of the Hepatitis Delta Antigen (HDAg) R0 region obtained in this study, showed considerable diversity among the local strains with a potential subgroup formation within clade I. The multiple sequence alignment of predicted amino acids within clade I showed many uncommon amino acid substitutions within some conserved regions that are crucial for replication and assembly of HDV.ConclusionsThe studied strains showed a range of genetic diversity within HDV clade I. There is clustering of sequences into more than one group, along with formation of potential subgroup within clade I. Clustering shows the genetic closeness of strains and indicates a common origin of spread of HDV infection. Further phylogeny-based studies may provide more information about subgroup formation within clade I and may be used as an effective tool in checking and/or preventing the spread of hepatitis D virus infection in this region.

Comprehensive analysis of mutations in the hepatitis delta virus genome based on full-length sequencing in a nationwide cohort study and evolutionary pattern during disease progression

“…As glycine and lysine have similar characteristics as serine and arginine, and besides the lower importance of serine 2 compared with serine 177 and the ability of methyltransferase to recognize lysine as a substrate [2,55,56], these substitutions may not hinder HDAg function. The other amino acid substitutions, including those in positions 198 and 202, are similar to already reported residues from other countries; the possible functional effect on HDAg properties requires further analyses [8,11,19,20].…”

“…These isolates had a close relation to African strains, and phylogenetic tree topology indicated that these strains (D32, D33 and D34) might be the basal lineage that diverged earlier from the other Iranian HDV genotype 1. Although people in this region of the country are considered in close relationship with their relatives from Afghanistan and Pakistan, phylogenetic trees constructed by the C-terminal of L-HDAg, either from nucleotides or amino acids, did not cluster these sequences together with reported HDV genotype 1 isolates from Pakistan [19] nor from Afghanistan (data not shown) [16]. This discrepancy may be explained by the use of a very small portion of HDV genome for evolutionary analysis in these studies.…”

“…These cases were from a province located at the border with Pakistan and Afghanistan, where HDV infection is prevalent [9,12]. The formation of a potential subgroup of HDV clade 1 by Pakistani isolates was previously reported [19]. However, neighbour-joining analysis of our cases with the reported sequences from these two countries, representing the C-terminal domain of the L-HDAg, did not cluster them together (data not shown) stressing that partial genome analysis is not sufficient for evolutionary analysis.…”

“…However, in both cases the superseded residue has the same characteristics as the main one, hence the role of the amino acids might not be impeded by these replacements. There are also some features of heterogeneity in the packaging signal region including residues 198 and 202, as defined based on previously reported sequences from other countries [8,19], whose potential implications require further functional analyses.…”

“…In contrast, several countries in the Middle East are considered endemic regions for HDV infections [9][10][11][12][13]. Despite partial or full genome analyses of HDV reported from distinct geographical areas [14,15], there are limited data available on the molecular evolution of HDV from this region, particularly Iran [9,[16][17][18][19]. In the current cross-sectional and longitudinal study, we analysed the fulllength genome as well as the entire HDAg coding sequence of HDV isolates from a large set of HDV antibody positive patients (n = 34) from different parts of Iran.…”