From molecules to tissues: Host-cell responses to infection

病毒从进入细胞到病毒复制和组装，都依赖宿主资源来支持它们的复制。由于它们有限的编码能力，病毒已经进化出劫持、解除和重新利用这些宿主资源的机制，以促进它们的复制。这些相互作用跨越多个层面，包括不同的分子（DNA、RNA和蛋白质）和细胞途径。该规划的目的是采用无偏见的循证方法，确定在不同病原体之间保守的宿主因素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对病毒感染作出反应的理解。我们将与罗莎琳德富兰克林研究所（RFI， Harwell校区）和MRC蛋白磷酸化和泛素化单位（MRC PPU，邓迪大学）合作，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，以及它们对细胞和组织中支持感染和共感染的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，以及这些方法是否具有特异性或广泛应用于病毒。该规划的发现将通过确定新的以宿主为基础的干预治疗靶点，使国际病毒学界受益，并加强CVR作为国际领先的病毒研究中心的声誉。

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.