Ecology and species barriers of emerging bat hepatitis B viruses

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Infection with hepatitis B virus (HBV) is one of the most important viral infections worldwide with nearly 370 million chronically infected humans, causing more than 600,000 hepatitis B related deaths due to the sequelae of this disease. Although a protective vaccine is available, vaccine efficacy, viral escape-mutations and costs hinder complete HBV eradication. Besides primate HBV, other members of the family Hepadnaviridae are known from North-American rodents (squirrels and woodchuck) and birds. Due to a usually strong organ- and species-specificity of Hepadnaviridae these highly divergent non-primate viruses are not considered a possible source of primate (and human) re-infection. However, we recently detected novel Hepadnaviridae in Central American and African bats that are closely related to primate and human HBV in genomic domains critically involved in viral entry and infectivity. The exact role of these bat hepadnaviruses in hepadnaviral evolution remains to be determined. Critically, it needs to be analyzed whether these bat viruses may represent a reservoir for primate and/or human infection. This proposal focuses primarily on gaining insight into the ecology of bat hepadnaviruses by analyzing respective bats species. The host barrier for recent bat hepadnaviruses including a possible zoonotic potential will be determined by already established laboratory models including infection experiments using primary hepatocytes from different origin.