ABSTRACT

The hepatitis Delta virus (HDV) causes the most severe form of liver infection of all viral hepatitis. It is a globally distributed agent, and its genetic variability allows it to be organized into 8 genotypes with different geographical distributions. Its oldest report occurred in the 1930s, in South America. In this continent, genotype 3 (HDV-3) seems to be exclusive and the most frequently isolated. It is responsible for the most severe form of HDV infection, in contrast when the infection manifests itself in indigenous populations, where, it seems, it can appear asymptomatic and is more sensitive to treatment. The phylogenetic relationship of HDV-3 with the other genotypes is the most distant, having a direct evolutionary link with the last ancestor common to all HDV genotypes. These informations supports a hypothesis that the geographic origin of HDV is in South America, and may be associated with indigenous populations. Based on this information, the study aimed to describe the evolutionary dynamics of HDV and its evolutionary history in the South American continent, analyzing genomic portions of viral specimens isolated from patients from indigenous and non-indigenous populations, along with sequences already deposited in a genomics database of all eight genotypes. The analyzes showed that the most recent common ancestor of HDV- 3 was dated in 1940 and indicated that the dispersion may have started in Brazil, spreading to Venezuela, Peru and Colombia later. There was an exponential increase in the effective number of infections between the 1940s and 1980s, years after the first report of the presence of HDV in the continent during the outbreak of Labrea Black Fever, suggesting that the virus continued to spread and increase the number of cases decades after the first reports. In the new millennium, the analysis showed a decrease in the epidemiological levels of HDV, probably due to the implantation of the vaccine against its auxiliary virus, hepatitis B virus, and serological screening methods implemented in blood banks. The partial analyzes of the temporal phylogeny and dating of the last common ancestor to all HDV genotypes allowed to observe that it circulated between the nineteenth and twentieth centuries, around 1911. When considering the conclusions obtained with genotype 3 and its position in the cladistic distribution of HDV phylogeny (the only branch directly linked to the tree's root), it can be assumed that this ancestor was circulating in South America. During this period, an intense settlement of the Amazon region occurred, marked by initial contacts between hitherto isolated indigenous populations with individuals from several different locations in the country and the world, generating a possibility that this will be the first focus of HDV dissemination with consequent later dissemination across the globe.