Hepatitis delta virus (HDV) is responsible for the most severe form of acute and chronic viral hepatitis. We previously proposed that the Deltavirus genus is composed of eight major clades. However, few sequences were available to confirm this classification. Moreover, little is known about the structural and functional consequences of HDV variability. One practical consequence is the failure of most quantification assays to properly detect or quantify plasmatic HDV RNA. Between 2001 and 2014, 2,152 HDV strains were prospectively collected and genotyped in our reference laboratory by means of nucleotide sequencing and extensive phylogenetic analyses of a 400-nucleotide region of the genome (R0) from nucleotides 889 to 1289 encompassing the 3′ end of the delta protein–coding gene. In addition, the full-length genome sequence was generated for 116 strains selected from the different clusters, allowing for in-depth characterization of the HDV genotypes and subgenotypes. This study confirms that the HDV genus is composed of eight genotypes (HDV-1 to HDV-8) defined by an intergenotype similarity >85% or >80%, according to the partial or full-length genome sequence, respectively. Furthermore, genotypes can be segregated into two to four subgenotypes, characterized by an intersubgenotype similarity >90% (>84% for HDV-1) over the whole genome sequence. Systematic analysis of genome and protein sequences revealed highly conserved functional nucleotide and amino acid motifs and positions across all (sub)genotypes, indicating strong conservatory constraints on the structure and function of the genome and the protein. Conclusion: This study provides insight into the genetic diversity of HDV and a clear view of its geographical localization and allows speculation as to the worldwide spread of the virus, very likely from an initial African origin. (Hepatology 2017;66:1826–1841)

中文翻译：

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三角洲病毒属的遗传多样性和全球分布：对2,152株临床菌株的研究

三角洲肝炎病毒（HDV）是急性和慢性病毒性肝炎的最严重形式。我们以前曾提出三角洲病毒属由八个主要进化枝组成。但是，很少有序列可用于确认该分类。此外，关于HDV变异性的结构和功能后果知之甚少。一个实际的后果是，大多数定量分析未能正确检测或定量血浆HDV RNA。在2001年至2014年之间，我们在参考实验室中通过核苷酸测序和对基因组400个核苷酸区域（R0），从889至1289位核苷酸（包含delta蛋白质编码基因的3'端）。另外，针对选自不同簇的116个菌株产生了全长基因组序列，从而允许对HDV基因型和亚基因型进行深入表征。这项研究证实，根据部分或全长基因组序列，HDV属由八个基因型（HDV-1至HDV-8）组成，它们之间的基因型相似性> 85％或> 80％。此外，基因型可以分为2-4个亚基因型，其特征是在整个基因组序列中亚基因型间的相似度> 90％（对于HDV-1> 84％）。对基因组和蛋白质序列的系统分析显示，所有（亚）基因型的核苷酸和氨基酸功能基序和位置均高度保守，结论：这项研究提供了对HDV遗传多样性的洞察力，以及对HDV地理定位的清晰认识，并使得人们可以推测该病毒在全球范围的传播，这很可能来自非洲最初的起源。（肝病学， 2017年； 66：1826–1841）