Global Distribution and Natural Recombination of Hepatitis D Virus: Implication of Kyrgyzstan Emerging HDVs in the Clinical Outcomes

Abstract

Discrepancies in human hepatitis delta virus (HDV) genotypes impact the virus’ biological behavior, clinical manifestation, and treatment response. Herein, this report aims to explore the role of recombination in the worldwide genotypic distribution and genetic diversity of HDV. Three-hundred-forty-eight human HDV full-length genomic sequences of ~1678 nt in length, isolated in twenty-eight countries worldwide between 1986 and 2018, were analysed. Similarity analysis and recombination mapping were performed, and forty-eight recombination events were identified, twenty-nine of which were isolated from Kyrgyzstan and determined to be involved in the diversity and extension of HDV sub-genotypes. HDV recombination occurred only between the genetically close genotypes (genotype 5 and genotype 2) or mainly within genotype 1, suggesting the complex replicative molecular mechanisms of HDV-RNA. The global distribution and classification of HDV genotypes have been updated, indicating that HDV recombination is one of the driving forces behind the biodiversity and the evolution of human HDV genomes. The outcome analysis suggests that the expansion of HDV sub-genotypes and the complex recombination networks might be related to the genomic character of Kyrgyzstan circulating strains and extensive mobility within countries and across borders. These findings will be of great importance in formulating more effective public health HDV surveillance strategies and guiding future molecular and epidemiological research to achieve better clinical outcomes.

Unbranched rod-like RNA is required for RNA editing of hepatitis delta virus genotype 2 and genotype 4

“…Regarding the amino acid sequences, the homologies among 9 HDV-2 S-HDAgs and L-HDAgs were found to be 85.2 % to 94.4 % and 86.0 % to 94.9 %, respectively. Notably, the HDV-2 and HDV-4 clones examined in this study were identified as belonging to the HDV-2a and HDV-4a subgenotypes ( Bahoussi et al., 2022 ; Le Gal et al., 2017 ).…”

“…To investigate whether the editing structures of HDV-2 and HDV-4 are present in African HDV genotypes, we focused on HDV-5, which is genetically most similar to HDV-2 and has been found recently in Kyrgyzstan ( Bahoussi et al., 2022 ; Le Gal et al., 2017 ). We examined the editing structure of HDV-5 and analyzed four HDV-5 sequences, two of which belonged to subgenotype HDV-5a (GenBank accession numbers JX888103 and JA417556), and two to HDV-5b (LT594482 and LT604958).…”

“…HDV RNA recombination has been observed in mixed-genotype infections and in cultured cells co-transfected with two HDV sequences ( Chao et al., 2015 ; Chao et al., 2017 ; Wang and Chao, 2005 ). Additionally, HDV recombinants have been identified through phylogenetic and recombination analyses ( Bahoussi et al., 2022 ; Lin et al., 2017 ). The presence of identical structural elements crucial for RNA editing in HDV strains of different genotypes further supports the notion that multiple RNA recombination events contribute to the generation of new HDV variants.…”

“…HDV-5 to HDV-8 are commonly found in individuals of African origin. Interestingly, HDV-5 has recently been reported circulating in Asia, specifically in Kyrgyzstan ( Bahoussi et al., 2022 ).…”

HDV RNA assays: Performance characteristics, clinical utility, and challenges

“…[6][7][8] In addition, a high level of spread and diversity of HDV genotypes, with considerable intergenotypic and intragenotypic recombination, drives the emergence of new strains and subgenotypes as reported in recent study in Central Asia. [9] Worldwide distribution of HDV genotypes and subgenotypes HDV genotypes and subgenotypes display distinct geographical distribution (Figure 1). [8] HDV-1 genotype is the most prevalent worldwide, is found in nearly all continents, and has a distinct subgenotype distribution.…”