Nebraska Center for Virology, School of Biological Sciences, University of Nebraska-Lincoln, Lincoln, NE 68583-0900, USA.
Virol J. 2011 Aug 1;8:379. doi: 10.1186/1743-422X-8-379.
In an effort to identify the evolutionary changes relevant to E2 function, within and between papillomavirus genera, we evaluated the E2 binding sites (E2BS)s inside the long-control-region (LCR), and throughout the genomes. We identified E2BSs in the six largest genera of papillomaviruses: Alpha, Beta, Gamma, Delta, Lambda, and Xi-papillomaviruses (128 genomes), by comparing the sequences with a model consensus we created from known functional E2BSs (HPV16, HPV18, BPV1). We analyzed the sequence conservation and nucleotide content of the 4-nucleotide spacer within E2BSs. We determined that there is a statistically significant difference in GC content of the four-nucleotide E2BS spacer, between Alpha and Delta-papillomaviruses, as compared to each of the other groups. Additionally, we performed multiple alignments of E2 protein sequences using members of each genus in order to identify evolutionary changes within the E2 protein.
When a phylogenetic tree was generated from E2 amino acid sequences, it was discovered that the alpha-papillomavirus genera segregates into two distinct subgroups (α1 and α2). When these subgroups were individually analyzed, it was determined that the subgroup α1 consensus E2BS favored a spacer of AAAA, whereas subgroup α2 favored the opposite orientation of the same spacer; TTTT. This observation suggests that these conserved inverted linkers could have functional importance.
为了鉴定与 E2 功能相关的进化变化，我们在乳头瘤病毒属内和属间评估了长控制区（LCR）内和整个基因组中的 E2 结合位点（E2BS）。我们通过将序列与我们从已知功能 E2BS（HPV16、HPV18、BPV1）创建的模型共识进行比较，在六个最大的乳头瘤病毒属中鉴定了 E2BS：Alpha、Beta、Gamma、Delta、Lambda 和 Xi-乳头瘤病毒（128 个基因组）。我们分析了 E2BS 内 4 个核苷酸间隔区的序列保守性和核苷酸含量。我们确定，与其他组相比，Alpha 和 Delta-乳头瘤病毒之间的 4 个核苷酸 E2BS 间隔区的 GC 含量存在统计学上的显著差异。此外，我们使用每个属的成员对 E2 蛋白序列进行了多重比对，以鉴定 E2 蛋白内的进化变化。
当从 E2 氨基酸序列生成系统发育树时，发现 Alpha 乳头瘤病毒属分为两个不同的亚组（α1 和 α2）。当分别分析这些亚组时，确定亚组α1 的 E2BS 一致序列有利于 AAAA 的间隔区，而亚组α2 则有利于相同间隔区的相反方向；TTTT。这一观察结果表明，这些保守的反向接头可能具有功能重要性。
