Bürck Carolin, Mund Andreas, Berscheminski Julia, Kieweg Lisa, Müncheberg Sarah, Dobner Thomas, Schreiner Sabrina
Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg, Germany.
Chromatin Structure and Function Group, Protein Signaling Program, The Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
J Virol. 2015 Nov 4;90(2):930-46. doi: 10.1128/JVI.01836-15. Print 2016 Jan 15.
Once transported to the replication sites, human adenoviruses (HAdVs) need to ensure decondensation and transcriptional activation of their viral genomes to synthesize viral proteins and initiate steps to reprogram the host cell for viral replication. These early stages during adenoviral infection are poorly characterized but represent a decisive moment in the establishment of a productive infection. Here, we identify a novel host viral restriction factor, KAP1. This heterochromatin-associated transcription factor regulates the dynamic organization of the host chromatin structure via its ability to influence epigenetic marks and chromatin compaction. In response to DNA damage, KAP1 is phosphorylated and functionally inactive, resulting in chromatin relaxation. We discovered that KAP1 posttranslational modification is dramatically altered during HAdV infection to limit the antiviral capacity of this host restriction factor, which represents an essential step required for efficient viral replication. Conversely, we also observed during infection an HAdV-mediated decrease of KAP1 SUMO moieties, known to promote chromatin decondensation events. Based on our findings, we provide evidence that HAdV induces KAP1 deSUMOylation to minimize epigenetic gene silencing and to promote SUMO modification of E1B-55K by a so far unknown mechanism.
Here we describe a novel cellular restriction factor for human adenovirus (HAdV) that sheds light on very early modulation processes in viral infection. We reported that chromatin formation and cellular SWI/SNF chromatin remodeling play key roles in HAdV transcriptional regulation. We observed that the cellular chromatin-associated factor and epigenetic reader SPOC1 represses HAdV infection and gene expression. Here, we illustrate the role of the SPOC1-interacting factor KAP1 during productive HAdV growth. KAP1 binds to the viral E1B-55K protein, promoting its SUMO modification, therefore illustrating a crucial step for efficient viral replication. Simultaneously, KAP1 posttranslational modification is dramatically altered during infection. We observed an HAdV-mediated decrease in KAP1 SUMOylation, known to promote chromatin decondensation events. These findings indicate that HAdV induces the loss of KAP1 SUMOylation to minimize epigenetic gene silencing and to promote the SUMO modification of E1B-55K by a so far unknown mechanism.
一旦转运至复制位点，人腺病毒（HAdV）需要确保其病毒基因组解聚并转录激活，以合成病毒蛋白并启动对宿主细胞进行重编程以实现病毒复制的步骤。腺病毒感染的这些早期阶段特征尚不明确，但却是建立有效感染的决定性时刻。在此，我们鉴定出一种新型宿主病毒限制因子KAP1。这种与异染色质相关的转录因子通过影响表观遗传标记和染色质压缩的能力来调节宿主染色质结构的动态组织。响应DNA损伤时，KAP1被磷酸化且功能失活，导致染色质松弛。我们发现，在HAdV感染期间，KAP1的翻译后修饰发生了显著改变，以限制这种宿主限制因子的抗病毒能力，这是有效病毒复制所需的关键步骤。相反，我们在感染过程中还观察到HAdV介导的KAP1 SUMO部分减少，已知这会促进染色质解聚事件。基于我们的发现，我们提供证据表明，HAdV诱导KAP1去SUMO化，以最小化表观遗传基因沉默，并通过一种迄今未知的机制促进E1B - 55K的SUMO修饰。
在此我们描述了一种新型的人腺病毒（HAdV）细胞限制因子，它揭示了病毒感染中非常早期的调节过程。我们报道染色质形成和细胞SWI/SNF染色质重塑在HAdV转录调控中起关键作用。我们观察到细胞染色质相关因子和表观遗传阅读器SPOC1抑制HAdV感染和基因表达。在此，我们阐述了SPOC1相互作用因子KAP1在HAdV有效生长过程中的作用。KAP1与病毒E1B - 55K蛋白结合，促进其SUMO修饰，因此说明了有效病毒复制的关键步骤。同时，在感染期间KAP1的翻译后修饰发生了显著改变。我们观察到HAdV介导的KAP1 SUMO化减少，已知这会促进染色质解聚事件。这些发现表明，HAdV诱导KAP1 SUMO化缺失，以最小化表观遗传基因沉默，并通过一种迄今未知的机制促进E1B - 55K的SUMO修饰。
