Hepatitis B viruses (HBVs), which are enveloped viruses with reverse-transcribed DNA genomes, constitute the family Hepadnaviridae. An outstanding feature of HBVs is their streamlined genome organization with extensive gene overlap. Remarkably, the ∼1,100 bp open reading frame (ORF) encoding the envelope proteins is fully nested within the ORF of the viral replicase P. Here, we report the discovery of a diversified family of fish viruses, designated nackednaviruses, which lack the envelope protein gene, but otherwise exhibit key characteristics of HBVs including genome replication via protein-primed reverse-transcription and utilization of structurally related capsids. Phylogenetic reconstruction indicates that these two virus families separated more than 400 million years ago before the rise of tetrapods. We show that HBVs are of ancient origin, descending from non-enveloped progenitors in fishes. Their envelope protein gene emerged de novo, leading to a major transition in viral lifestyle, followed by co-evolution with their hosts over geologic eras.

乙型肝炎病毒（HBV）是具有逆转录DNA基因组的包膜病毒，构成了Hepadnaviridae家族。乙型肝炎病毒的一个突出特点是其简化的基因组组织和广泛的基因重叠。值得注意的是，编码包膜蛋白的约1100 bp开放阅读框（ORF）完全嵌套在病毒复制酶P的ORF中。在此，我们报告发现了一种鱼蛋白家族，称为无节病毒，其缺乏包膜蛋白。乙型肝炎病毒（HBV）的主要特征，但包括通过蛋白引发的逆转录进行基因组复制和利用结构相关衣壳的HBV关键特征。系统发育重建表明，这两个病毒家族在四足动物崛起之前相隔了四亿多年前。我们表明，乙肝病毒起源于鱼类中的非包膜祖细胞，起源于古代。他们的包膜蛋白基因从头出现，导致病毒式生活方式发生重大转变，随后与他们的宿主在地质时代共同发展。