Heterogeneity and common features of defective hepatitis B virus genomes derived from spliced pregenomic RNA
Heterogeneity and common features of defective hepatitis B virus genomes derived from spliced pregenomic RNA
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DOI：
10.1006/viro.1997.8863
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发表时间：
1997-11-24
期刊：
影响因子：
3.7
通讯作者：
Will, H
中科院分区：
文献类型：
--
作者：
Gunther, S;Sommer, G;Will, H
据报道，从剪接RNA前基因组的包装和逆转录中衍生的乙肝病毒（HBV）基因组缺陷与慢性感染的进展有关。由于到目前为止只有两种具有相似剪接区域的类型被表征，我们推断可能存在额外的“剪接”基因组变体。因此，我们通过全长PCR从7例慢性乙肝病毒携带者的血清中分离出大量缺陷HBV基因组。通过克隆、亚基因组PCR和测序，发现其中48个含有由剪接引起的缺失。在每种血清中，共有11种类型的剪接基因组以不同的组合存在于10种不同的内含子切除中。这种多样性是由于在大多数（但不是所有）HBV基因型中存在5个剪接供体位点和4个受体位点的替代使用。所有剪接的基因组都共享复制所需的序列元件，以及pre-C和pre- genome/C mRNA和X mRNA的转录。此外，它们都含有X蛋白和pre-S/ core或pre-S/ core融合蛋白的编码区，但缺乏pre-S/S基因启动子。这些数据表明，剪接基因组具有丰富的HBV基因型依赖性多样性，其中可以表达各种异常的前核/核融合蛋白和正常的X蛋白，但没有功能包膜和P蛋白。这些基因组和编码蛋白可能在病毒的生命周期、持久性和发病机制中发挥作用。(C) 1997学术出版社。
Defective hepatitis B virus (HBV) genomes derived from packaging and reverse transcription of spliced RNA pregenomes were reported to be associated with progression to chronic infection. Since only two types with similarly spliced regions were characterized so far we reasoned that additional ''spliced'' genome variants may exist. Therefore, we isolated a large number of defective HBV genomes from sera of seven chronic carriers by full-length PCR. Forty-eight were found to contain deletions caused by splicing as identified by cloning, subgenomic PCR, and sequencing. In total, 11 types of spliced genomes derived from excision of 10 different introns were present in various combinations in each serum. This diversity resulted from alternative usage of five splice donor and four acceptor sites present in most but not all HBV genotypes. All spliced genomes shared sequence elements essential for replication as well as for transcription of the pre-C and pregenome/C mRNAs and the X mRNA. Moreover, all contained the coding regions for the X protein and for precore/core or precore/core fusion proteins but lacked the pre-S/S gene promoters. These data demonstrate substantial and HBV genotype-dependent diversity of spliced genomes from which a variety of aberrant precore/core fusion proteins and normal X protein but no functional envelope and P proteins could be expressed. These genomes and the encoded proteins may play a role in the viral life cycle, persistence, and pathogenesis. (C) 1997 Academic Press.