Ecology and species barriers of emerging bat hepatitis B viruses

乙肝病毒感染是世界范围内最重要的病毒感染之一，有近3.7亿慢性感染者，因该病的后遗症导致60多万人死于与乙肝相关的疾病。尽管有保护性疫苗可用，但疫苗效力、病毒逃逸突变和成本阻碍了彻底根除乙肝病毒。除了灵长类的乙肝病毒，肝导航病毒科的其他成员是从北美啮齿动物(松鼠和土拨鼠)和鸟类中得知的。由于肝导航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(和人类)再次感染的可能来源。然而，我们最近在中美洲和非洲蝙蝠中发现了与灵长类和人类乙肝病毒密切相关的新的肝导航病毒科，这些病毒在基因组领域与病毒进入和传染性密切相关。这些蝙蝠肝炎病毒在肝炎病毒进化中的确切作用仍有待确定。关键是，需要分析这些蝙蝠病毒是否可能是灵长类和/或人类感染的宿主。这项建议主要侧重于通过分析不同种类的蝙蝠来洞察蝙蝠肝病毒的生态。最近的蝙蝠肝病毒的宿主屏障，包括可能的人畜共患病潜力，将由已经建立的实验室模型来确定，包括使用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.