Ecology and species barriers of emerging bat hepatitis B viruses

乙型肝炎病毒（HBV）感染是世界上最重要的病毒感染之一，有近3.7亿人慢性感染，由于这种疾病的后遗症，导致60多万与乙型肝炎相关的死亡。虽然有一种保护性疫苗，但疫苗效力、病毒逃逸突变和成本阻碍了乙肝病毒的完全根除。除了灵长类乙型肝炎病毒，已知的其他乙型肝炎病毒科成员来自北美啮齿动物（松鼠和土拨鼠）和鸟类。由于肝病毒科通常具有很强的器官和物种特异性，这些高度分化的非灵长类病毒不被认为是灵长类动物（和人类）再感染的可能来源。然而，我们最近在中美洲和非洲蝙蝠中发现了新型肝炎病毒科，它们与灵长类动物和人类HBV在基因组区域密切相关，这些基因组区域与病毒进入和传染性密切相关。这些蝙蝠肝病毒在肝病毒进化中的确切作用仍有待确定。至关重要的是，需要分析这些蝙蝠病毒是否可能代表灵长类动物和/或人类感染的宿主。该提案主要集中在通过分析各自蝙蝠物种来深入了解蝙蝠肝炎病毒的生态学。最近的蝙蝠肝炎病毒的宿主屏障，包括可能的人畜共患潜力，将通过已经建立的实验室模型来确定，包括使用来自不同来源的原代肝细胞的感染实验。

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.