Exploring genetic diversity of hepatitis D virus full-length genome in Brazil: Discovery of a novel HDV-8 subgenotype beyond African borders

Hepatitis D virus (HDV) is currently classified into 8 genotypes (1 to 8) and several subgenotypes, with distinct distribution worldwide. However, due to the scarcity of complete genome sequences in databases, this classification is constantly being updated and tends to be regularly revisited in upcoming years as more sequence data becomes available. Aiming to increase knowledge about the genetic variability of HDV, this study presents the full-length genomes of 11 HDV samples collected in Brazil in endemic and non-endemic regions, including the first complete genomes of the genotypes 5 and 8 obtained outside Africa. We also determined the co-infecting HBV genotypes to investigate their prevalence among the HDV-infected individuals throughout the country. Whole genome sequencing confirmed our previous findings based on a partial fragment of the HDV genome, in which HDV subgenoypes 3c (9/11; 81.8 %), 5b (1/11; 9.1 %) and one HDV-8 sequence (1/11; 9.1 %) were detected. As previously observed, HDV-8 formed a distinct branch apart from subgenotypes 8a and 8b, a monophyletic clade representing a novel HDV-8 subgenotype, designated as 8c. Among HDV-3 samples, the main co-infecting HBV genotype found was HBV-F (4/8; 50 %), reflecting the higher incidence of this native South American genotype in the endemic Amazon Basin. Both samples infected with HDV-5 and HDV-8 were coinfected with HBV genotype E, also a genotype with African origin. Our findings based on complete genome sequence of HDV corroborated our results based on a partial region of the HDV genome of a novel HDV-8 subgenotype and reinforced the need to use full-length genomes to properly subdivide genotypes with very low intragroup genetic variability, such as HDV-3. The provision of these complete genomes is expected to contribute to the enrichment of sequence databases for future molecular and evolutionary investigations of HDV.