Sichero L, Villa L L
Instituto Ludwig de Pesquisa sobre o Câncer, São Paulo, SP, Brasil.
Braz J Med Biol Res. 2006 Jun;39(6):707-17. doi: 10.1590/s0100-879x2006000600002. Epub 2006 Jun 2.
Human papillomavirus genomes are classified into molecular variants when they present more than 98% of similarity to the prototype sequence within the L1 gene. Comparative nucleotide sequence analyses of these viruses have elucidated some features of their phylogenetic relationship. In addition, human papillomavirus intratype variability has also been used as an important tool in epidemiological studies of viral transmission, persistence and progression to clinically relevant cervical lesions. Until the present, little has been published concerning the functional significance of molecular variants. It has been shown that nucleotide variability within the long control region leads to differences in the binding affinity of some cellular transcriptional factors and to the enhancement of the expression of E6 and E7 oncogenes. Furthermore, in vivo and in vitro studies revealed differences in E6 and E7 biochemical and biological properties among molecular variants. Nevertheless, further correlation with additional functional information is needed to evaluate the significance of genome intratypic variability. These results are also important for the development of vaccines and to determine the extent to which immunization with L1 virus-like particles of one variant could induce antibodies that cross-neutralize other variants.
当人乳头瘤病毒基因组在L1基因内与原型序列的相似度超过98%时，它们被归类为分子变体。对这些病毒进行的比较核苷酸序列分析阐明了它们系统发育关系的一些特征。此外，人乳头瘤病毒型内变异性也已被用作病毒传播、持续存在以及发展为临床相关宫颈病变的流行病学研究中的一项重要工具。到目前为止，关于分子变体的功能意义发表的内容很少。研究表明，长控制区内的核苷酸变异性会导致一些细胞转录因子结合亲和力的差异，并导致E6和E7致癌基因表达增强。此外，体内和体外研究揭示了分子变体之间E6和E7生化及生物学特性的差异。然而，需要进一步与其他功能信息建立关联，以评估基因组型内变异性的意义。这些结果对于疫苗开发以及确定用一种变体的L1病毒样颗粒进行免疫接种能够诱导交叉中和其他变体的抗体的程度也很重要。
