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。虽然强有力和适当的T细胞应答对宿主有益，但弱或不适当的应答可能是无效的，甚至具有有害影响。许多因素影响T细胞对病毒感染或癌症发展的应答的质量，其中主要是感染部位的微环境、受影响的细胞类型以及在感染的情况下病毒的变异性。通过了解T细胞应答在许多不同病毒感染和病毒相关癌症，特别是HBV相关HCC中有效控制所需的关键因素，我们的目标是确定增强和控制免疫应答的靶点，作为改善几种重要人类疾病结局的一种方式。虽然我的小组的主要重点是T细胞反应，但小组的一个子集专注于重要的抗病毒限制因子IFITM3，已知其限制>15种RNA病毒，包括甲型流感病毒，HIV和丙型肝炎病毒，但限制机制仍然未知。由于IFITM 3与其他IFITM家族成员的高度同源性，很少有关于IFITM 3的结论性数据发表。已知IFITM3内的单核苷酸多态性（SNP）可以防止其病毒限制，但其机制仍然未知。这种有趣的蛋白质留给我们几个未回答的问题，我们的目标是使用新的试剂来检测这种蛋白质，以阐明病毒限制发生的机制。

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