Oncogenic herpesvirus KSHV triggers hallmarks of alternative lengthening of telomeres
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Timothy P Lippert Paulina Marzec Aurora Idilli Grzegorz Sarek Aleksandra Vancevska Mark Bower Paul J Farrell Päivi M Ojala Niklas Feldhahn Simon BoultonAbstract
To achieve replicative immortality, cancer cells must activate telomere maintenance mechanisms to prevent telomere shortening. ~85% of cancers circumvent telomeric attrition by re-expressing telomerase, while the remaining ~15% of cancers induce alternative lengthening of telomeres (ALT), which relies on break-induced replication (BIR) and telomere recombination. Although ALT tumours were first reported over 20 years ago, the mechanism of ALT induction remains unclear and no study to date has described a cell-based model that permits the induction of ALT. Here, we demonstrate that infection with Kaposi’s sarcoma herpesvirus (KSHV) induces sustained acquisition of ALT-like features in previously non-ALT cell lines. KSHV-infected cells acquire hallmarks of ALT activity that are also observed in KSHV-associated tumour biopsies. Down-regulating BIR impairs KSHV latency, suggesting that KSHV co-opts ALT for viral functionality. This study uncovers KSHV infection as a means to study telomere maintenance by ALT and reveals features of ALT in KSHV-associated tumours.
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Journal Nature Communications
Volume 12
Issue number 1
Pages 512
Available online
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Publisher website (DOI) 10.1038/s41467-020-20819-4
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Europe PubMed Central 33479235
Pubmed 33479235
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