Tumor viruses and replicative immortality--avoiding the telomere hurdle.
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.
Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden.
Xinsong
X
Chen
Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden.
Siamak Akbari
SA
Kamranvar
Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden. Electronic address: maria.masucci@ki.se.
Maria G
MG
Masucci
D000818:Animals; D002472:Cell Transformation, Viral; D016922:Cellular Senescence / Q000235:genetics; D042822:Genomic Instability; D006801:Humans; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism / Q000821:virology; D009858:Oncogenic Viruses / Q000502:physiology*; D016615:Telomere / Q000235:genetics* / Q000378:metabolism*; D014412:Tumor Virus Infections / Q000235:genetics / Q000378:metabolism / Q000821:virology; D014779:Virus Replication
Alternative lengthening of telomere; Genomic instability; Telomerase; Telomere; Tumor virus