Origin and Evolution of Hepatitis B Virus

MBAYED, V.; FLICHMAN, D.; TORRES, C.; PEZZANO, S.; PIÑEIRO Y LEONE, F. G.; CAMPOS, R.

Buenos Aires

Simposio; INTERNACIONAL SYMPOSIUM OF THE INTERNACIONAL MASTER IN BIOMEDICAL SCIENCES. UNIVERSITY OF BUENOS AIRES AND ALBERT LUDWINGS UNIVERSITY OF FREIBURG; 2008

Universidad de Buenos Aires, Albert Ludwings University of Freiburg

The hepatitis B virus is the cause of one of the most frequent viral infections of humans worldwide. There are approximately 350 million people infected with HBV in the world. Chronic infection with HBV is closely associated with fatal liver diseases such as cirrhosis and hepatocellular carcinoma. Approximately 1 million people die of HBV-associated diseases every year. About 45% of the world´s population live in a high prevalence area, 43% in  a moderate prevalence area and only 12% live in low prevalence areas. Genetic variability of this virus is reflected by the eight different genomic groups or genotypes (A-H) described so far which show geographical differentiation (Genotype > 8%; Subgenotype < 8%). Since each genotype seems to have restricted geographical distribution, such data is an invaluable tool in tracing the molecular evolution, pattern and modes of HBV spread. As a consequence of the multiple overlapping reading frames and the lack of polymerase proof-reading activity the HBV has an error frequencies intermediate between DNA and RNA viruses. The rate of nucleotide substitution of HBV is uncertain. Despite the availability of multiple whole-genome sequences for comparison, there is as yet no consensus on the evolutionary relationships or divergence times of the HBV and, hence, on its epidemiological history. The theories for the origin of HBV are controversial. The aim of this study was analyze isolates from our region and explore how different rates of evolution fit with the emergence of sub genotypes in relationship with those theories. The distribution of HBV genotypes in the Americas may reflect the past migration of human populations to the New World. In particular, genotypes A and D may be the signature of the more recent European colonization, including slave trade from Africa, whereas genotypes B and C indicate the latest arrival of people from Southeast Asia. In contrast, genotypes F and H have been proposed to have arrived in the New World with the first human migrants from Asia more than 20,000 years ago or, alternatively, to be a recent interspecies transmission. In South America Genotype F is the most prevalent; particularly on native American populations. On the west coast, subtypes 1a and 1b were found it, while in the north-east and central regions subtypes 2, 3 and 4 are the most prevalent. The emergence of Genotypes and Sub genotypes depends on the size and density of a population in a region. Sub genotypes F1b and F4 are consequence of an emergence. Considering a substitution rate  of 1 - 5 .10-5 n/s/y, the coalescent analysis suggests a Most Recent Common Ancestor  (MRCA) of approximately 800 - 1000 years ago. On the XVI and XVII centuries there were different places in the Andean region (Cuzco, Potosi) with more than 100,000 inhabitants which supports the hypothesis of the emergence 800 - 1000 years ago of the Sub genotypes  found today in Latin America.