Geographic Distribution and Genetic Variability of Hepatitis Delta Virus Genotype I

Abstract

Three genotypes of hepatitis delta virus (HDV) have been identified, each with different geographic distributions and disease associations. To better define the geographic distribution and genetic variability of HDV genotype I, and to evaluate the extent of genome variability in populations with different patterns of HDV infection, we have analyzed the sequence of HDV RNA in the sera of 72 patients from different areas. Patients were primarily residents of the United States and areas in and around Greece, including Archangelos, Rhodes. All sequences obtained belonged to HDV genotype I, confirming the wide geographic distribution of this genotype and its predominance in Europe and the United States. In contrast to previous studies, phylogenetic analysis of this large and diverse group of sequences, along with all available previously published HDV sequences, showed no well-defined subtypes within genotype I. Low sequence diversity was found for isolates from the United States, Archangelos, Turkey, and Albania, suggesting that HDV was introduced more recently and/or from fewer sources into these areas as compared to mainland Greece, Italy, and north Africa, where sequence diversity is much greater. The low sequence diversity among isolates from Archangelos is particularly interesting in light of the unusually mild pattern of HDV disease found in this community. Comparison of nucleic acid and amino acid sequences within and among genotypes indicated both highly conserved regions as well as genotype-specific sequences that could be related to functional differences. The most distinctive of the latter was that corresponding to the C-terminal 19–20 amino acids of the long form of hepatitis delta antigen, which is highly conserved within each genotype but considerably diverged among them.