From molecules to tissues: Host-cell responses to infection

从分子到组织：宿主细胞对感染的反应

• 批准号: MC_UU_00034/2
• 负责人: Chris Boutell
• 金额: $ 422.4万
• 依托单位: University of Glasgow
• 依托单位国家: 英国
• 项目类别: Intramural
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MC_UU_00034%2F2
• 关键词: molecules; tissues; Host; cell; responses

Viruses are dependent on host resources to support their replication, from entry into cells to virus replication and assembly. Due to their limited coding capacity, viruses have evolved mechanisms to hijack, disarm and repurpose these host resources to promote their replication. These interactions span multiple levels, including different molecules (DNA, RNA and protein) and cellular pathways. The aim of this programme is to apply an unbiased evidence-based approach to identify common networks of host factors and host responses to infection that are conserved between divergent pathogens, unifying our understanding of how cells and tissues respond to virus infection. We will partner with the Rosalind Franklin Institute (RFI, Harwell Campus) and MRC Protein Phosphorylation and Ubiquitylation Unit (MRC PPU, University of Dundee) to identify how these networks are formed, the repertoire of cellular and viral proteins involved, and their functional contribution to viral fitness in both cells and tissues that support infection and coinfection. Knowledge gained from this programme will reveal the approaches employed by viruses to subvert host cells and whether these approaches are specific or broadly utilised across viruses. Discoveries from this programme will benefit the international virology community through the identification of new host-based therapeutic targets for intervention, reinforcing the reputation of the CVR as an international leading centre for virus research.

病毒依赖于宿主资源来支持其复制，从进入细胞到病毒复制和组装。由于其有限的编码能力，病毒已经进化出了劫持、解除和重新利用这些宿主资源以促进其复制的机制。这些相互作用跨越多个层次，包括不同的分子（DNA，RNA和蛋白质）和细胞途径。该计划的目的是应用公正的循证方法来确定不同病原体之间保守的宿主因子和宿主对感染的反应的共同网络，统一我们对细胞和组织如何应对病毒感染的理解。我们将与罗莎琳德·富兰克林研究所（RFI，Harwell Campus）和MRC蛋白磷酸化和泛素化单位（MRC PPU，邓迪大学）合作，以确定这些网络是如何形成的，所涉及的细胞和病毒蛋白的库，以及它们对支持感染和共感染的细胞和组织中病毒适应性的功能贡献。从该计划中获得的知识将揭示病毒破坏宿主细胞的方法，以及这些方法是特异性的还是广泛用于病毒。该计划的发现将通过确定新的基于宿主的治疗靶点来使国际病毒学界受益，从而加强CVR作为国际领先病毒研究中心的声誉。

项目成果

Single-genome analysis reveals heterogeneous association of the Herpes Simplex Virus genome with H3K27me2 and the reader PHF20L1 following infection of human fibroblasts

单基因组分析揭示了感染人成纤维细胞后单纯疱疹病毒基因组与 H3K27me2 和阅读器 PHF20L1 的异质关联

• DOI: 10.1101/2023.12.03.569766
• 发表时间: 2023
• 作者: Francois A

Novel Antiviral Molecules against Ebola Virus Infection.

• DOI: 10.3390/ijms241914791
• 发表时间: 2023-09-30
• 期刊: International journal of molecular sciences
• 影响因子: 5.6

BTN3A3 evasion promotes the zoonotic potential of influenza A viruses

• DOI: 10.1038/s41586-023-06261-8
• 发表时间: 2023-06-28
• 期刊: NATURE
• 影响因子: 64.8
• 作者: Pinto, Rute Maria;Bakshi, Siddharth;Palmarini, Massimo
• 通讯作者: Palmarini, Massimo