Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden.
Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden.
Semin Cancer Biol. 2014 Jun;26:43-51. doi: 10.1016/j.semcancer.2014.01.006. Epub 2014 Jan 28.
Tumor viruses promote cell proliferation in order to gain access to an environment suitable for persistence and replication. The expression of viral products that promote growth transformation is often accompanied by the induction of multiple signs of telomere dysfunction, including telomere shortening, damage of telomeric DNA and chromosome instability. Long-term survival and progression to full malignancy require the bypassing of senescence programs that are triggered by the damaged telomeres. Here we review different strategies by which tumor viruses interfere with telomere homeostasis during cell transformation. This frequently involves the activation of telomerase, which assures both the integrity and functionality of telomeres. In addition, recent evidence suggests that oncogenic viruses may activate a recombination-based mechanism for telomere elongation known as Alternative Lengthening of Telomeres (ALT). This error-prone strategy promotes genomic instability and could play an important role in viral oncogenesis.
肿瘤病毒促进细胞增殖，以便进入适合持续和复制的环境。促进生长转化的病毒产物的表达常常伴随着端粒功能障碍的多种迹象的诱导，包括端粒缩短、端粒 DNA 损伤和染色体不稳定。长期存活并进展为完全恶性需要绕过由受损端粒引发的衰老程序。在这里，我们回顾了肿瘤病毒在细胞转化过程中干扰端粒动态平衡的不同策略。这通常涉及端粒酶的激活，它保证了端粒的完整性和功能。此外，最近的证据表明，致癌病毒可能激活一种称为端粒延伸的替代延长（ALT）的基于重组的端粒延长机制。这种易错策略促进了基因组不稳定性，并可能在病毒致癌中发挥重要作用。
