Herpesvirus telomeric repeats facilitate genomic integration into host telomeres and mobilization of viral DNA during reactivation
Herpesvirus telomeric repeats facilitate genomic integration into host telomeres and mobilization of viral DNA during reactivation
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DOI：
10.1084/jem.20101402
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发表时间：
2011-03-14
影响因子：
15.3
通讯作者：
Osterrieder, Nikolaus
中科院分区：
文献类型：
--
作者：
Kaufer, Benedikt B.;Jarosinski, Keith W.;Osterrieder, Nikolaus
一些疱疹病毒，特别是嗜淋巴细胞病毒，如马立克氏病病毒（MDV）和人类疱疹病毒6（HHV-6），将其DNA整合到宿主染色体中。MDV和HHV-6等疱疹病毒在其线性基因组的任一末端具有与宿主端粒相同的端粒重复序列（TMR）。使用MDV作为自然病毒宿主模型，我们表明疱疹病毒TMR促进病毒基因组整合到宿主端粒中，并且整合对于潜伏期和淋巴瘤形成的建立是重要的。整合到宿主端粒中也有助于从感染的静止状态重新激活。我们的研究结果和许多疱疹病毒中存在的TMR表明，由病毒TMR介导的整合是一种保守的机制，它确保了细胞分裂期间宿主细胞中忠实的病毒基因组维持，并允许休眠病毒基因组的有效动员。这一发现是特别重要的，因为再活化是病毒在易感个体之间传播的关键，并且是疱疹病毒持续进化和存活所必需的。
Some herpesviruses, particularly lymphotropic viruses such as Marek's disease virus (MDV) and human herpesvirus 6 (HHV-6), integrate their DNA into host chromosomes. MDV and HHV-6, among other herpesviruses, harbor telomeric repeats (TMRs) identical to host telomeres at either end of their linear genomes. Using MDV as a natural virus-host model, we show that herpesvirus TMRs facilitate viral genome integration into host telomeres and that integration is important for establishment of latency and lymphoma formation. Integration into host telomeres also aids in reactivation from the quiescent state of infection. Our results and the presence of TMRs in many herpesviruses suggest that integration mediated by viral TMRs is a conserved mechanism, which ensures faithful virus genome maintenance in host cells during cell division and allows efficient mobilization of dormant viral genomes. This finding is of particular importance as reactivation is critical for virus spread between susceptible individuals and is necessary for continued herpesvirus evolution and survival.