HCMV US2 INHIBITS MHC CLASS II ANTIGEN PRESENTATION

HCMV US2 抑制 MHC II 类抗原呈递

• 批准号: 6518544
• 负责人: David C. Johnson
• 金额: $ 37.75万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-03-01 至 2005-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6518544
• 关键词: Adenoviridae; MHC class II antigen; antigen presentation; cellular immunity; cytomegalovirus; helper T lymphocyte; inhibitor /antagonist; laboratory mouse; laboratory rabbit; macrophage; monoclonal antibody; mutant; recombinant virus; tissue /cell culture; transfection /expression vector; virus antigen; virus protein

Human cytomegalovirus (HCMV) is a ubiquitous virus that infects a substantial fraction of the U.S. population, leading to lifelong persistent or latent infections. HCMV is normally quite benign but causes serious problems in immunocompromised or immunosuppressed patients, especially after bone marrow and solid organ transplantation where the virus causes pneumonia, graft rejection, and disseminated diseases. In AIDS, HCMV causes retinitis, frequently seen in late-stages of the disease, and this seriously decreases the quality of life for AIDS patients. HCMV-induced retinitis was common, in 20-55% of AIDS patients, before Highly Active Anti Retroviral Therapy (HAART). Since HAART, retinitis and other HCMV-induced diseases have declined dramatically. It is not clear whether HAART will continue to keep HIV in decline and, if HIV rebounds, HCMV-induced retinitis will likely reestablish itself as a major problem. Moreover, the present trend toward increased numbers of bone marrow and solid tissue transplants will cause continued escalation of HCMV disease. Cellular immune responses are critical to controlling HCMV replication and spread, especially following virus reactivation from latency. However, HCMV uses a panel of proteins to evade the host immune system, viral proteins that block recognition by natural killer cells and T lymphocytes. The applicant has recently reported an HCMV protein, US2, which is the first-described viral inhibitor of the MHC class II antigen presentation pathway that signals virus infection to CD4+ T cells. These observations provide an important new insight into how HCMV can hide out or persist in MHC class II pathway functions in a virus-infected cell, to present endogenous rather than exogenous antigens. In the studies proposed herein he would characterize the effects of US2 in macrophages and endothelial cells and determine the molecular basis for how US2 inhibits the class II pathway.

人巨细胞病毒(HCMV)是一种普遍存在的病毒，可感染人 很大一部分美国人口，导致终生坚持或 潜伏感染。巨细胞病毒通常是相当良性的，但会在 免疫受损或免疫抑制的患者，尤其是在骨髓移植后 和实体器官移植，在那里病毒引起肺炎，移植物 排斥反应和播散性疾病。在艾滋病患者中，人巨细胞病毒会引起视网膜炎， 常见于疾病的晚期，这严重降低了 艾滋病患者的生活质量。人巨细胞病毒引起的视网膜炎很常见，20%-55% 在艾滋病患者中，在高效抗逆转录病毒治疗(HAART)之前。自.以来 HAART、视网膜炎和其他由HCMV引起的疾病急剧下降。它 尚不清楚HAART是否会继续使艾滋病毒保持下降趋势，如果艾滋病毒 反弹，巨细胞病毒引起的视网膜炎可能会重新成为主要的 有问题。此外，目前骨髓数量增加的趋势 而固体组织移植会导致人巨细胞病毒病的持续升级。 细胞免疫反应是控制巨细胞病毒复制和 传播，特别是在病毒从潜伏期重新激活之后。然而，人巨细胞病毒 使用一组蛋白质来逃避宿主免疫系统，病毒蛋白质 自然杀伤细胞和T淋巴细胞的区块识别。申请人有 最近报道了一种人巨细胞病毒蛋白US2，这是第一个被描述的病毒 信号转导病毒的MHC-II类抗原提呈途径的抑制物 感染CD4+T细胞。这些观察提供了一个重要的新见解 人巨细胞病毒是如何隐藏或维持在MHC II类途径中的功能的 病毒感染的细胞，呈现内源性抗原而不是外源性抗原。在……里面 在这里提出的研究他将表征US2的影响在 巨噬细胞和内皮细胞，并确定US2如何的分子基础 抑制II类途径。