HCMV US2 INHIBITS MHC CLASS II ANTIGEN PRESENTATION

人巨细胞病毒（HCMV）是一种普遍存在的病毒， 美国人口的很大一部分，导致终身持续或 潜伏感染HCMV通常是相当良性的，但会导致严重的问题， 免疫功能低下或免疫抑制患者，尤其是骨髓移植后 和实体器官移植，其中病毒引起肺炎， 排斥和传播性疾病。在艾滋病中，HCMV导致视网膜炎， 在疾病的晚期经常看到，这严重降低了 艾滋病患者的生活质量。HCMV引起的视网膜炎是常见的，在20-55% 艾滋病患者，在高效抗逆转录病毒治疗（HAART）之前。以来 HAART、视网膜炎和其他由HCMV引起的疾病已大幅下降。它 目前尚不清楚HAART是否会继续保持艾滋病毒的下降，如果艾滋病毒 当HCMV引起的视网膜炎反弹时，HCMV引起的视网膜炎可能会重新成为一种主要的 问题.此外，目前骨髓数量增加的趋势 并且实体组织移植将导致HCMV疾病的持续升级。 细胞免疫应答对于控制HCMV复制至关重要， 传播，特别是在病毒从潜伏期重新激活之后。然而，HCMV 使用一组蛋白质来逃避宿主免疫系统， 阻断自然杀伤细胞和T淋巴细胞的识别。申请人已经 最近报道了HCMV蛋白US 2，这是第一个描述的病毒 信号传导病毒的MHC II类抗原呈递途径的抑制剂 感染CD 4 + T细胞。这些观察提供了一个重要的新见解 HCMV如何隐藏或持续存在于MHC II类通路中， 病毒感染的细胞，呈递内源性而不是外源性抗原。在 在本文提出的研究中，他将描述US 2在 巨噬细胞和内皮细胞，并确定US 2 抑制II类途径。

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.