Intrinsic Immunity

内在免疫力

• 批准号: MC_UU_12014/5
• 负责人: Chris Boutell
• 金额: $ 390.54万
• 依托单位: University of Glasgow
• 依托单位国家: 英国
• 项目类别: Intramural
• 财政年份: 2013
• 资助国家: 英国
• 起止时间: 2013 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MC_UU_12014%2F5
• 关键词: Intrinsic; Immunity

Dr Chris Boutell, Lead Investigator, MRC-University of Glasgow Centre for Virus Research (CVR), University of GlasgowThe modification of proteins regulates many important aspects of cell biology, including host immunity to infection. Viruses have therefore evolved strategies to utilise or suppress pathways that regulate protein modification to overcome host defences to infection, thereby enhancing their replication, spread, and disease burden. However, these key interactions remain largely undefined at a biochemical level. Work within this programme focuses on two pathways, namely ubiquitin and SUMO (Small Ubiquitin-like MOdifier), which we and others have shown to play an important role in the regulation of host immunity. Our aim is to define the activity of core enzymes that influence the outcome of infection, using herpes simplex virus 1 (HSV-1) as a model DNA virus. These studies will reveal unique insight into the mechanisms that regulate host immunity during DNA virus infection, as well as uncovering fundamental principles that regulate other important areas of cell biology relevant to human disease, for example carcinogenesis. By understanding these principles we aim to develop new targeted approaches for future therapeutic intervention to treat viral infections pertinent to public health.

克里斯·布特尔博士，首席研究员，格拉斯哥大学病毒研究中心（CVR），格拉斯哥大学蛋白质的修饰调节细胞生物学的许多重要方面，包括宿主对感染的免疫力。因此，病毒已经进化出利用或抑制调节蛋白质修饰的途径的策略，以克服宿主对感染的防御，从而增强它们的复制、传播和疾病负担。然而，这些关键的相互作用在生物化学水平上仍然很不确定。该计划的工作重点是两个途径，即泛素和SUMO（小泛素样调节剂），我们和其他人已经证明在调节宿主免疫中发挥重要作用。我们的目的是确定影响感染结果的核心酶的活性，使用单纯疱疹病毒1型（HSV-1）作为模型DNA病毒。这些研究将揭示DNA病毒感染期间调节宿主免疫力的机制的独特见解，并揭示调节与人类疾病相关的其他重要细胞生物学领域的基本原则，例如致癌作用。通过理解这些原则，我们的目标是为未来的治疗干预开发新的靶向方法，以治疗与公共卫生相关的病毒感染。

项目成果

Novel Role for Protein Inhibitor of Activated STAT 4 (PIAS4) in the Restriction of Herpes Simplex Virus 1 by the Cellular Intrinsic Antiviral Immune Response.

• DOI: 10.1128/jvi.03055-15
• 发表时间: 2016-05
• 期刊: Journal of virology
• 影响因子: 5.4
• 作者: Conn KL;Wasson P;McFarlane S;Tong L;Brown JR;Grant KG;Domingues P;Boutell C
• 通讯作者: Boutell C

Distinct temporal roles for the promyelocytic leukaemia (PML) protein in the sequential regulation of intracellular host immunity to HSV-1 infection.

• DOI: 10.1371/journal.ppat.1006769
• 发表时间: 2018-01
• 期刊: PLoS pathogens
• 影响因子: 6.7
• 作者: Alandijany T;Roberts APE;Conn KL;Loney C;McFarlane S;Orr A;Boutell C
• 通讯作者: Boutell C

SUMO Ligase Protein Inhibitor of Activated STAT1 (PIAS1) Is a Constituent Promyelocytic Leukemia Nuclear Body Protein That Contributes to the Intrinsic Antiviral Immune Response to Herpes Simplex Virus 1.

• DOI: 10.1128/jvi.00426-16
• 发表时间: 2016-07-01
• 期刊: Journal of virology
• 影响因子: 5.4
• 作者: Brown JR;Conn KL;Wasson P;Charman M;Tong L;Grant K;McFarlane S;Boutell C
• 通讯作者: Boutell C

The Fate of Speckled Protein 100 (Sp100) During Herpesviruses Infection.

• DOI: 10.3389/fcimb.2020.607526
• 发表时间: 2020
• 期刊: Frontiers in cellular and infection microbiology
• 影响因子: 5.7
• 作者: Collados Rodríguez M

Constitutive TRIM22 Expression in the Respiratory Tract Confers a Pre-Existing Defence Against Influenza A Virus Infection.

• DOI: 10.3389/fcimb.2021.689707
• 发表时间: 2021
• 期刊: Frontiers in cellular and infection microbiology
• 影响因子: 5.7
• 作者: Charman M;McFarlane S;Wojtus JK;Sloan E;Dewar R;Leeming G;Al-Saadi M;Hunter L;Carroll MW;Stewart JP;Digard P;Hutchinson E;Boutell C
• 通讯作者: Boutell C