Moens U, Johansen T, Johnsen J I, Seternes O M, Traavik T
Department of Virology, University of Tromsø, Norway.
Virus Genes. 1995;10(3):261-75. doi: 10.1007/BF01701816.
The human polyomavirus BK (BKV) has a proven oncogenic potential, but its contribution to tumorigenesis under natural conditions remains undetermined. As for other primate polyomaviruses, the approximately 5.2 kbp double-stranded circular genome of BKV has three functional regions: the coding regions for the two early (T, t antigens) and four late (agno, capsid proteins; VP1-3) genes separated by a noncoding control region (NCCR). The NCCR contains the origin of replication as well as a promoter/enhancer with a mosaic of cis-acting elements involved in the regulation of both early and late transcription. Since the original isolation of BKV in 1971, a number of other strains have been identified. Most strains reveal a strong sequence conservation in the protein coding regions of the genome, while the NCCR exhibits considerable variation between different BKV isolates. This variation is due to deletions, duplications, and rearrangements of a basic set of sequence blocks. Comparative studies have proven that the anatomy of the NCCR may determine the transcriptional activities governed by the promoter/enhancer, the host cell tropism and permissivity, as well as the oncogenic potential of a given BKV strain. In most cases, however, the NCCR sequence of new isolates was determined after the virus had been passaged several times in more or less arbitrarily chosen cell cultures, a process known to predispose for NCCR rearrangements. Following the development of the polymerase chain reaction (PCR), it has become feasible to obtain naturally occurring BKV NCCRs, and their sequences, in samples taken directly from infected human individuals. Hence, the biological significance of BKV NCCR variation may be studied without prior propagation of the virus in cell culture. Such variation has general interest, because the BKV NCCRs represent typical mammalian promoter/enhancers, with a large number of binding motifs for cellular transacting factors, which can be conveniently handled for experimental purposes. This communication reviews the naturally occurring BKV NCCR variants, isolated and sequenced directly from human samples, that have been reported so far. The sequences of the different NCCRs are compared and analyzed for the presence of proven and putative cellular transcription factor binding sites. Differences in biological properties between BKV variants are discussed in light of their aberrant NCCR anatomies and the potentially modifying influence of transacting factors.
人类多瘤病毒BK（BKV）具有已被证实的致癌潜力，但其在自然条件下对肿瘤发生的作用仍未确定。与其他灵长类多瘤病毒一样，BKV约5.2kbp的双链环状基因组有三个功能区域：两个早期基因（T、t抗原）和四个晚期基因（agno、衣壳蛋白；VP1 - 3）的编码区，由一个非编码控制区（NCCR）分隔。NCCR包含复制起点以及一个启动子/增强子，其具有参与早期和晚期转录调控的顺式作用元件的镶嵌结构。自1971年首次分离出BKV以来，已鉴定出许多其他毒株。大多数毒株在基因组的蛋白质编码区显示出很强的序列保守性，而NCCR在不同的BKV分离株之间表现出相当大的差异。这种差异是由于一组基本序列块的缺失、重复和重排所致。比较研究已证明，NCCR的结构可能决定由启动子/增强子控制的转录活性、宿主细胞嗜性和允许性，以及特定BKV毒株的致癌潜力。然而，在大多数情况下，新分离株的NCCR序列是在病毒在或多或少任意选择的细胞培养物中传代几次后确定的，这一过程已知易引发NCCR重排。随着聚合酶链反应（PCR）技术的发展，直接从受感染的人类个体采集的样本中获取天然存在的BKV NCCR及其序列已成为可行的。因此，无需事先在细胞培养中繁殖病毒，就可以研究BKV NCCR变异的生物学意义。这种变异具有普遍意义，因为BKV NCCR代表典型的哺乳动物启动子/增强子，具有大量细胞反式作用因子的结合基序，便于用于实验目的。本通讯综述了迄今报道的直接从人类样本中分离和测序的天然存在的BKV NCCR变体。比较并分析了不同NCCR的序列，以确定已证实和推测的细胞转录因子结合位点的存在。根据BKV变体异常的NCCR结构以及反式作用因子的潜在修饰影响，讨论了它们生物学特性的差异。
