Sommer G, Günther S, Sterneck M, Otto S, Will H
Heinrich-Pette-Institut für experimentalle Virologie und immunologie an, Universität Hamburg, Germany.
Virology. 1997 Dec 22;239(2):402-12. doi: 10.1006/viro.1997.8898.
Sequence heterogeneity of hepatitis B virus (HBV) is increasingly recognized to play a role in virus-host interaction. We have used a recently established method for HBV full-length genome amplification to search for novel types of HBV variants and to investigate further the sequence heterogeneity of HBV genome populations. Using this method, a substantial fraction of HBV genomes much shorter than wildtype size was found in some sera and liver biopsies from infected patients. Cloning and sequencing of a number of these HBV genomes as well as hybridization studies revealed a new minor class of HBV genomes with an internal poly(dA) sequence approximately 60 to more than 100 nucleotides long in 4 of 10 patients. The 5'-ends of the internal poly(dA) sequences are located at positions corresponding to the authentic processing/polyadenylation sites of the RNA pregenome, whereas the positions of the 3'-ends are variable due to different sizes of adjacent deletions. These data suggest that the poly(A) tail of the pregenomic RNA is occasionally reverse transcribed by the HBV P-protein and during this process a deletion seems to be introduced into the DNA minus strand. We propose a mechanism by which this could be accomplished during DNA minus strand synthesis.
乙型肝炎病毒（HBV）的序列异质性在病毒与宿主相互作用中所起的作用日益受到认可。我们采用了一种最近建立的HBV全长基因组扩增方法，以寻找新型HBV变异体，并进一步研究HBV基因组群体的序列异质性。使用该方法，在一些受感染患者的血清和肝活检样本中发现了相当一部分比野生型大小短得多的HBV基因组。对许多此类HBV基因组进行克隆和测序以及杂交研究发现，在10名患者中的4名患者中存在一类新的次要HBV基因组，其具有大约60至100多个核苷酸长的内部聚（dA）序列。内部聚（dA）序列的5'端位于与RNA前基因组的真实加工/聚腺苷酸化位点相对应的位置，而3'端的位置因相邻缺失的大小不同而可变。这些数据表明，前基因组RNA的聚（A）尾偶尔会被HBV P蛋白逆转录，并且在此过程中似乎会在DNA负链中引入缺失。我们提出了一种在DNA负链合成过程中可能实现这一过程的机制。
