Dill Jennifer A, Camus Alvin C, Leary John H, Di Giallonardo Francesca, Holmes Edward C, Ng Terry Fei Fan
Department of Pathology, University of Georgia, Athens, Georgia, USA.
Marie Bashir Institute for Infectious Diseases and Biosecurity, Charles Perkins Centre, School of Life and Environmental Sciences, and Sydney Medical School, University of Sydney, Sydney, NSW, Australia.
J Virol. 2016 Aug 12;90(17):7920-33. doi: 10.1128/JVI.00832-16. Print 2016 Sep 1.
Hepadnaviruses (hepatitis B viruses [HBVs]) are the only animal viruses that replicate their DNA by reverse transcription of an RNA intermediate. Until recently, the known host range of hepadnaviruses was limited to mammals and birds. We obtained and analyzed the first amphibian HBV genome, as well as several prototype fish HBVs, which allow the first comprehensive comparative genomic analysis of hepadnaviruses from four classes of vertebrates. Bluegill hepadnavirus (BGHBV) was characterized from in-house viral metagenomic sequencing. The African cichlid hepadnavirus (ACHBV) and the Tibetan frog hepadnavirus (TFHBV) were discovered using in silico analyses of the whole-genome shotgun and transcriptome shotgun assembly databases. Residues in the hydrophobic base of the capsid (core) proteins, designated motifs I, II, and III, are highly conserved, suggesting that structural constraints for proper capsid folding are key to capsid protein evolution. Surface proteins in all vertebrate HBVs contain similar predicted membrane topologies, characterized by three transmembrane domains. Most striking was the fact that BGHBV, ACHBV, and the previously described white sucker hepadnavirus did not form a fish-specific monophyletic group in the phylogenetic analysis of all three hepadnaviral genes. Notably, BGHBV was more closely related to the mammalian hepadnaviruses, indicating that cross-species transmission events have played a major role in viral evolution. Evidence of cross-species transmission was also observed with TFHBV. Hence, these data indicate that the evolutionary history of the hepadnaviruses is more complex than previously realized and combines both virus-host codivergence over millions of years and host species jumping.
Hepadnaviruses are responsible for significant disease in humans (hepatitis B virus) and have been reported from a diverse range of vertebrates as both exogenous and endogenous viruses. We report the full-length genome of a novel hepadnavirus from a fish and the first hepadnavirus genome from an amphibian. The novel fish hepadnavirus, sampled from bluegills, was more closely related to mammalian hepadnaviruses than to other fish viruses. This phylogenetic pattern reveals that, although hepadnaviruses have likely been associated with vertebrates for hundreds of millions of years, they have also been characterized by species jumping across wide phylogenetic distances.
嗜肝DNA病毒（乙型肝炎病毒[HBV]）是唯一通过RNA中间体逆转录来复制其DNA的动物病毒。直到最近，已知嗜肝DNA病毒的宿主范围还仅限于哺乳动物和鸟类。我们获得并分析了首个两栖类HBV基因组以及几种原型鱼类HBV，这使得首次能够对来自四类脊椎动物的嗜肝DNA病毒进行全面的比较基因组分析。蓝鳃太阳鱼嗜肝DNA病毒（BGHBV）是通过内部病毒宏基因组测序鉴定出来的。非洲丽鱼科嗜肝DNA病毒（ACHBV）和西藏林蛙嗜肝DNA病毒（TFHBV）是利用全基因组鸟枪法和转录组鸟枪法组装数据库的计算机分析发现的。衣壳（核心）蛋白疏水基部中的残基，命名为基序I、II和III，高度保守，这表明衣壳正确折叠的结构限制是衣壳蛋白进化的关键。所有脊椎动物HBV中的表面蛋白都含有相似的预测膜拓扑结构，其特征是具有三个跨膜结构域。最引人注目的是，在对所有三种嗜肝DNA病毒基因的系统发育分析中，BGHBV、ACHBV和先前描述的白鲑嗜肝DNA病毒并未形成鱼类特有的单系类群。值得注意的是，BGHBV与哺乳动物嗜肝DNA病毒的关系更为密切，这表明跨物种传播事件在病毒进化中发挥了主要作用。在TFHBV中也观察到了跨物种传播的证据。因此，这些数据表明嗜肝DNA病毒的进化历史比以前认识到的更为复杂，它结合了数百万年的病毒-宿主共同进化和宿主物种跳跃。
嗜肝DNA病毒可导致人类严重疾病（乙型肝炎病毒），并且已在多种脊椎动物中作为外源性和内源性病毒被报道。我们报告了一种来自鱼类的新型嗜肝DNA病毒的全长基因组以及首个来自两栖类的嗜肝DNA病毒基因组。从蓝鳃太阳鱼中采样的新型鱼类嗜肝DNA病毒与哺乳动物嗜肝DNA病毒的关系比与其他鱼类病毒的关系更为密切。这种系统发育模式表明，尽管嗜肝DNA病毒可能已经与脊椎动物相伴数亿年，但它们的特征还包括跨越广泛系统发育距离的物种跳跃。
