Oncogenic herpesvirus KSHV triggers hallmarks of alternative lengthening of telomeres.
Oncogenic herpesvirus KSHV triggers hallmarks of alternative lengthening of telomeres.
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DOI：
10.1038/s41467-020-20819-4
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发表时间：
2021-01-21
影响因子：
16.6
通讯作者：
Boulton SJ
中科院分区：
文献类型：
--
作者：
Lippert TP;Marzec P;Idilli AI;Sarek G;Vancevska A;Bower M;Farrell PJ;Ojala PM;Feldhahn N;Boulton SJ
为了实现复制永生，癌细胞必须激活端粒维持机制，以防止端粒缩短。~85%的癌症通过重新表达端粒酶来避免端粒磨损，而其余~15%的癌症通过断裂诱导复制(BIR)和端粒重组诱导端粒交替延长(ALT)。虽然ALT肿瘤最早在20多年前被报道，但ALT诱导的机制仍然不清楚，到目前为止还没有研究描述允许诱导ALT的基于细胞的模型。在这里，我们证明了感染Kaposi肉瘤疱疹病毒(KSHV)诱导在以前的非ALT细胞系中持续获得ALT样特征。感染KSHV的细胞获得ALT活性的特征，这在KSHV相关的肿瘤活检中也可以观察到。下调BIR会削弱KSHV的潜伏期，这表明KSHV选择ALT来实现病毒功能。这项研究揭示了KSHV感染是研究ALT维持端粒的一种手段，并揭示了KSHV相关肿瘤中ALT的特征。约15%的癌症可引起端粒交替延长(ALT)以激活端粒维持。在这里，作者揭示了感染Kaposi肉瘤疱疹病毒(KSHV)诱导在以前的非ALT细胞系中获得ALT样特征。
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. ~15% of cancers induce alternative lengthening of telomeres (ALT) to activate telomere maintenance. Here, the authors reveal that infection with Kaposi’s sarcoma herpesvirus (KSHV) induces acquisition of ALT-like features in previously non-ALT cell lines.
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影响因子：
5.4
作者：
Dheekollu, Jayaraju;Chen, Horng-Shen;Lieberman, Paul M.
通讯作者：
Lieberman, Paul M.
影响因子：
16.8
作者：
Arnoult N;Karlseder J
通讯作者：
Karlseder J
影响因子：
12.3
作者：
Carpenter AE;Jones TR;Lamprecht MR;Clarke C;Kang IH;Friman O;Guertin DA;Chang JH;Lindquist RA;Moffat J;Golland P;Sabatini DM
通讯作者：
Sabatini DM
影响因子：
16
作者：
Davis, Zoe H.;Verschueren, Erik;Jang, Gwendolyn M.;Kleffman, Kevin;Johnson, Jeffrey R.;Park, Jimin;Von Dollen, John;Maher, M. Cyrus;Johnson, Tasha;Newton, William;Jaeger, Stefanie;Shales, Michael;Horner, Julie;Hernandez, Ryan D.;Krogan, Nevan J.;Glaunsinger, Britt A.
通讯作者：
Glaunsinger, Britt A.
影响因子：
3.7
作者：
Cotter, MA;Robertson, ES
通讯作者：
Robertson, ES