Laboratoire de Microbiologie Clinique, Hôpitaux Universitaires de Paris Seine Saint-Denis, Site Avicenne, Université Sorbonne Paris Cité, Bobigny, France.
Centre national de référence des virus des hépatites B, C et Delta, Laboratoire de Virologie, Bobigny, France.
Hepatology. 2017 Dec;66(6):1826-1841. doi: 10.1002/hep.29574. Epub 2017 Oct 30.
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.
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).
乙型肝炎 delta 病毒（HDV）是导致最严重的急性和慢性病毒性肝炎的原因。我们之前提出，Deltavirus 属由八个主要分支组成。然而，只有少数序列可用于确认这种分类。此外，人们对 HDV 变异的结构和功能后果知之甚少。一个实际的后果是，大多数定量检测法都无法正确检测或定量检测血浆 HDV RNA。在 2001 年至 2014 年期间，我们的参考实验室通过核苷酸测序和对基因组 400 个核苷酸区域（R0）进行广泛的系统发育分析，前瞻性地收集和分型了 2152 株 HDV 株，该区域核苷酸 889 至 1289 ，包括 delta 蛋白编码基因的 3'末端。此外，还从不同的聚类中选择了 116 株全长基因组序列，以便对 HDV 基因型和亚型进行深入表征。这项研究证实，HDV 属由 8 个基因型（HDV-1 至 HDV-8）组成，根据部分或全长基因组序列，其种间相似性分别大于 85%或大于 80%。此外，基因型可以分为两个到四个亚型，整个基因组序列的种间相似性大于 90%（HDV-1 为 84%）。对基因组和蛋白质序列的系统分析揭示了所有（亚）基因型之间高度保守的功能核苷酸和氨基酸基序和位置，表明对基因组和蛋白质的结构和功能有很强的保守限制。
这项研究提供了对 HDV 遗传多样性的深入了解，并清楚地了解了其地理定位，并推测了病毒在全球的传播情况，很可能最初起源于非洲。（《肝脏病学》2017 年；66：1826-1841）。
