Department of Microbiology-Immunology, Northwestern University, Feinberg, School of Medicine, Chicago Avenue, Morton 6-681, Chicago, IL 60611, USA.
Future Microbiol. 2013 Dec;8(12):1547-57. doi: 10.2217/fmb.13.127.
HPVs are the causative agents of cervical and other anogenital cancers. HPVs infect stratified epithelia and link their productive life cycles to cellular differentiation. Low levels of viral genomes are stably maintained in undifferentiated cells and productive replication or amplification is restricted to differentiated suprabasal cells. Amplification is dependent on the activation of the ATM DNA damage factors that are recruited to viral replication centers and inhibition of this pathway blocks productive replication. The STAT-5 protein appears to play a critical role in mediating activation of the ATM pathway in HPV-positive cells. While HPVs need to activate the DNA damage pathway for replication, cervical cancers contain many genomic alterations suggesting that this pathway is circumvented during progression to malignancy.
人乳头瘤病毒（HPV）是导致宫颈癌和其他生殖器官癌症的病原体。HPV 感染复层上皮组织，并将其有性生命周期与细胞分化联系起来。低水平的病毒基因组在未分化细胞中稳定维持，而有性复制或扩增仅限于分化的基底上层细胞。扩增依赖于 ATM 细胞损伤因子的激活，这些因子被募集到病毒复制中心，抑制该途径会阻断有性复制。STAT-5 蛋白似乎在 HPV 阳性细胞中介导 ATM 途径的激活中发挥关键作用。虽然 HPV 需要激活 DNA 损伤途径进行复制，但宫颈癌包含许多基因组改变，表明在向恶性肿瘤进展过程中，该途径被绕过。
