Antiviral role of Condensin II

项目摘要--作者：Michelle S./O‘Connor，Christine M. 入侵的病原体，如病毒和细菌，迅速改变细胞 动态平衡。细胞动态平衡是由表观遗传学和更高的 有序的染色质组织，而凝集素II复合体起着至关重要的作用 在调控这些过程中。然而，我们对凝聚素II的理解 在感染过程中对宿主细胞DNA组织的贡献很小。人类 巨细胞病毒(HCMV)是一种普遍存在的疱疹病毒，流行于美国70%的地区 人口。免疫功能受损的人患上 人巨细胞病毒感染的并发症，目前尚无治疗方法或疫苗。 因此，对开发新的治疗策略存在明显的、未得到满足的需求， 这就需要更好地了解宿主和病原体之间的关系。我们的 初步数据显示，人巨细胞病毒感染上调凝集素II蛋白 NCAPD3，NCAPD3限制病毒复制，尽管潜在的 机制仍不清楚。这项提议的总体目标是 确定人巨细胞病毒感染对NCAPD3/凝聚素II介导的影响 染色质组织和基因转录。我们的中心假设是 NCAPD3/COMPAIN II通过其调控能力限制HCMV裂解复制 染色质可及性。我们建议通过以下方式来检验这一假设 目标：AIM1。检测NCAPD3表达对人巨细胞病毒裂解感染的影响。 AIM2.识别NCAPD3介导的基因表达和染色质变化 应对巨细胞病毒感染的可获得性。我们的预期结果是 提案包括定义CAP-D3如何通过 染色体调节，同时揭示了这种新型抗病毒药物 在感染过程中，因子受到调节。影响：结果将提供全面的 了解宿主细胞在应对病毒感染时的动态，并为 为未来开发抗人巨细胞病毒感染的新疗法奠定基础 和疾病。

PROJECT SUMMARY – LONGWORTH, MICHELLE S./ O’CONNOR, CHRISTINE M. Invading pathogens, such as viruses and bacteria, rapidly alter cellular homeostasis. Cellular homeostasis is maintained by both epigenetics and higher order chromatin organization, and the condensin II complex plays essential roles in regulating these processes. However, our understanding of condensin II’s contribution to host cell DNA organization during infection is minimal. Human cytomegalovirus (HCMV) is a ubiquitous herpesvirus, prevalent in >70% of the US population. Immune compromised individuals are at heightened risk for complications from HCMV infection, for which there is currently no cure or vaccine. Thus, there is a clear, unmet need for development of novel therapeutic strategies, necessitating a better understanding of the host-pathogen relationship. Our preliminary data show that HCMV infection upregulates the condensin II protein NCAPD3, and that NCAPD3 restricts viral replication, although the underlying mechanisms remain unknown. The overall objective of this proposal is to determine the impact of HCMV infection on NCAPD3/condensin II-mediated chromatin organization and gene transcription. Our central hypothesis is that NCAPD3/condensin II restricts HCMV lytic replication through its ability to regulate chromatin accessibility. We propose to test this hypothesis through the following aims: AIM1. Determine the effects of NCAPD3 expression on HCMV lytic infection. AIM2. Identify NCAPD3-mediated changes to gene expression and chromatin accessibility in response to HCMV infection. The expected outcomes of our proposal include defining how CAP-D3 combats HCMV infection through chromosomal regulation, while revealing the means by which this novel antiviral factor is regulated during infection. Impact: Results will provide a comprehensive understanding of host cell dynamics in response to viral infection and lay the foundation for future development of novel therapeutics to combat HCMV infection and disease.