Cellular immunity and genetic restriction of Influenza, Hepatitis C virus infection and Hepatitis B associated heptocellular carcinoma.

流感、丙型肝炎病毒感染和乙型肝炎相关肝细胞癌的细胞免疫和遗传限制。

• 批准号: MC_UU_00008/11
• 负责人: Tao Dong
• 金额: $ 188.2万
• 依托单位: University of Oxford
• 依托单位国家: 英国
• 项目类别: Intramural
• 财政年份: 2017
• 资助国家: 英国
• 起止时间: 2017 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MC_UU_00008%2F11
• 关键词: Cellular; immunity; genetic; restriction; Influenza

Human infections, cancer development and the course of disease are mainly influenced by T cell responses. While a robust and appropriate T cell response is beneficial to the host, a weak or inappropriate response can be ineffective or even have a detrimental effect. Numerous factors influence the quality of the T cell response to viral infections or cancer development, predominant among them being the microenvironment of the infection site, the type of cells affected and in the case of infection, the variability of the virus. By understanding the key factors required for efficient control by the T cell response in a number of different viral infections and viral associated cancers, in particular HBV associated HCC, we aim to identify targets to augment and control the immune response as a way of improving the outcome of in several important human diseases. While my group's main focus is T cell responses, a subset of the group focus on the important anti-viral restriction factor IFITM3, which is known to restrict >15 RNA viruses including Influenza A virus, HIV and Hepatitis C virus, however the mechanism of restriction is still unknown. Little conclusive data on IFITM3 is published due to its high homology to other IFITM family members. A single nucleotide polymorphism (SNP) within IFITM3 is known to prevent its viral restriction but again the mechanism for this is unknown. This interesting protein leaves us with several unanswered questions and we aim to characterise this protein using novel reagents in order to elucidate the mechanism by which viral restriction occurs.

人类感染，癌症发展和疾病进程主要受T细胞反应的影响。尽管健壮且适当的T细胞反应对宿主有益，但弱或不适当的反应可能是无效的，甚至可能产生不利影响。许多因素会影响T细胞对病毒感染或癌症发展的反应质量，其中主要是感染部位的微环境，受影响的细胞类型，在感染的情况下，病毒的变异性。通过了解许多不同病毒感染和病毒相关癌症（尤其是HBV相关的HCC）中T细胞反应有效控制所需的关键因素，我们旨在识别靶标，以增强和控制免疫反应，以改善几种重要人类疾病的结果。尽管我小组的主要重点是T细胞反应，但该组的一部分集中在重要的抗病毒限制因子IFITM3上，该因子已知限制了> 15种RNA病毒，包括流感病毒病毒，HIV和丙型肝炎病毒，但是限制机制仍然未知。由于其与其他IFITM家庭成员的同源性很高，因此发表了有关IFITM3的最终确定数据。已知IFITM3内的单个核苷酸多态性（SNP）可防止其病毒限制，但再次尚不清楚。这种有趣的蛋白质给我们带来了几个未解决的问题，我们的目的是使用新型试剂来表征这种蛋白质，以阐明发生病毒限制的机制。

项目成果

The antigenic anatomy of SARS-CoV-2 receptor binding domain.

• DOI: 10.1016/j.cell.2021.02.032
• 发表时间: 2021-04-15
• 期刊: Cell
• 影响因子: 64.5
• 作者: Dejnirattisai W;Zhou D;Ginn HM;Duyvesteyn HME;Supasa P;Case JB;Zhao Y;Walter TS;Mentzer AJ;Liu C;Wang B;Paesen GC;Slon-Campos J;López-Camacho C;Kafai NM;Bailey AL;Chen RE;Ying B;Thompson C;Bolton J;Fyfe A;Gupta S;Tan TK;Gilbert-Jaramillo J;James W;Knight M;Carroll MW;Skelly D;Dold C;Peng Y;Levin R;Dong T;Pollard AJ;Knight JC;Klenerman P;Temperton N;Hall DR;Williams MA;Paterson NG;Bertram FKR;Siebert CA;Clare DK;Howe A;Radecke J;Song Y;Townsend AR;Huang KA;Fry EE;Mongkolsapaya J;Diamond MS;Ren J;Stuart DI;Screaton GR
• 通讯作者: Screaton GR

The Early Antibody-Dependent Cell-Mediated Cytotoxicity Response Is Associated With Lower Viral Set Point in Individuals With Primary HIV Infection.

• DOI: 10.3389/fimmu.2018.02322
• 发表时间: 2018
• 期刊: Frontiers in immunology
• 影响因子: 7.3
• 作者: Chen X;Lin M;Qian S;Zhang Z;Fu Y;Xu J;Han X;Ding H;Dong T;Shang H;Jiang Y
• 通讯作者: Jiang Y