The DNA damage response promotes polyomavirus JC infection by nucleus to cytoplasm NF- kappaB activation
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- 作者：Martyn K. White ; Anna Bellizzi ; Gabriele Ibba ; Valeria Pietropaolo…
- 关键词：Progressive multifocal leukoencephalopathy ; Polyomavirus JC ; DNA damage response ; Nuclear factor kappa ; B
- 刊名：Virology Journal
- 出版年：2017
- 出版时间：December 2017
- 年：2017
- 卷：14
- 期：1
- 全文大小：1922KB
- 刊物主题：Virology;
- 出版者：BioMed Central
- ISSN：1743-422X
- 卷排序：14
文摘
BackgroundInfection of glial cells by human neurotropic polyomavirus JC (JCV), the causative agent of the CNS demyelinating disease progressive multifocal leukoencephalopathy (PML), rapidly inflicts damage to cellular DNA. This activates DNA damage response (DDR) signaling including induction of expression of DNA repair factor Rad51. We previously reported that Rad51 co-operates with the transcription factor NF-κB p65 to activate JCV early transcription. Thus Rad51 induction by JCV infection may provide positive feedback for viral activation early in JCV infection. DDR is also known to stimulate NF-κB activity, a phenomenon known as nucleus to cytoplasm or “inside-out” NF-κB signaling, which is initiated by Ataxia telangiectasia mutated (ATM) protein, a serine/threonine kinase recruited and activated by DNA double-strand breaks. Downstream of ATM, there occurs a series of post-translational modifications of NF-κB essential modulator (NEMO), the γ regulatory subunit of inhibitor of NF-κB (IκB) kinase (IKK), resulting in NF-κB activation.