Hepatitis Delta Virus Genetic Variability From Genotypes I Ii Iii to Eight Major Clades

Service de Bactériologie, Virologie, Hygiène, Laboratoire Associé au Centre National de Référence des hépatites B et C, Hôpital Avicenne, Assistance Publique - Hôpitaux de Paris, Université Paris 13, EA3406, 93009 Bobigny Cedex, France [email protected]

1 Viral Genetics of HBV and HDV 152

2 Nucleotide Similarity Approach: The Notion of Genotypes 155

3 Phylogenetic Analyses of African HDVs 157

3.1 Patients 157

3.2 Analysis of the R0 Region 157

3.3 Full-Length Genome Analysis 159

3.4 Use of sHD Gene Sequence for Phylogenetic Analyses 160

4 HD Protein and RNA Secondary Structure 162

5 HDV Phylogeography 164

5.1 HDV Genetic Distances and Geography 164

5.2 Co-epidemiological Speciation of HBV and HDV 164

5.3 HDV Genetic Variability and Clinical Patterns 165

6 Proposal for the Deltavirus Genus Classification 165

References 167

Abstract Hepatitis D virus (HDV) is a satellite of hepatitis B virus (HBV) for transmission and propagation, and infects nearly 20 million people worldwide. The HDV genome is composed of a compact circular single-stranded negative RNA genome with extensive intramolecular complementarity. Along with epidemiological, geographic distribution and pathological patterns, the variability of HDV has been limited to three genotypes and two subtypes that have been characterized to date. Recently, extensive phylogenetic reconstructions based on the delta antigen gene and full-length genome sequence data, have shown a wide and probably ancient radiation of African lineages, suggesting that the genetic variability of HDV is much more complex than previously thought. Indeed, sequences previously affiliated with genotype IIb should now be considered as belonging to clade 4 (HDV-4) and African HDV sequences segregate within four additional clades: HDV-5, HDV-6, HDV-7 and HDV-8. These results bring the geographic distribution of HDV closer to the genetic variability of its helper HBV

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