A novel immunomodulatory function for E3/49K the first secreted adenovirus protein

E3/49K（第一个分泌型腺病毒蛋白）的新型免疫调节功能

• 批准号: BB/D002877/1
• 负责人: Hans-Gerhard Burgert
• 金额: $ 32.26万
• 依托单位: University of Warwick
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2006
• 资助国家: 英国
• 起止时间: 2006 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FD002877%2F1
• 关键词: novel; immunomodulatory; function; E3; 49K

Human adenoviruses cause acute and persistent infections of the respiratory- and gastrointestinal tract, and the eye. On the other hand, adenoviruses are also used therapeutically as vectors for gene- and cancer therapy. We are interested in the different strategies adenoviruses use to evade the host immune system and cause persistent infections and differential disease. By investigating the molecular interactions between adenovirus E3 proteins and immunologically important host molecules we previously demonstrated that E3 proteins exhibit a variety of immunomodulatory functions that facilitate immune evasion. Thus far, only E3 proteins from two Ads (both from subgroup C) of the 51 human Ads have been functionally characterized. Here, we focus on E3/49K, an E3 protein unique to Ads of the largest subgroup D. Our previous studies together with the new data presented below identify E3/49K as the first secreted E3 protein, and suggest a novel, fundamentally different immunomodulatory E3 activity that is not directed to infected cells, as expected, but rather to uninfected lymphocytes. Our major aim is to characterize the E3/49K function and identify its cellular target molecules.

人腺病毒引起呼吸道、胃肠道和眼睛的急性和持续性感染。另一方面，腺病毒也在治疗上用作基因和癌症治疗的载体。我们感兴趣的是腺病毒使用不同的策略来逃避宿主免疫系统，并导致持续感染和差异性疾病。通过研究腺病毒E3蛋白和免疫学上重要的宿主分子之间的分子相互作用，我们以前证明了E3蛋白表现出多种免疫调节功能，促进免疫逃避。到目前为止，只有E3蛋白的两个广告（都来自亚组C）的51个人类广告的功能特征。在这里，我们专注于E3/49 K，一种E3蛋白，它是最大亚群D的广告所特有的。我们以前的研究以及下面提供的新数据将E3/49 K鉴定为第一个分泌的E3蛋白，并表明一种新的、根本不同的免疫调节E3活性，其不像预期的那样针对感染的细胞，而是针对未感染的淋巴细胞。我们的主要目的是表征E3/49 K的功能并鉴定其细胞靶分子。

项目成果

Sorting Motifs in the Cytoplasmic Tail of the Immunomodulatory E3/49K Protein of Species D Adenoviruses Modulate Cell Surface Expression and Ectodomain Shedding.

D 种腺病毒免疫调节 E3/49K 蛋白细胞质尾部的分选基序调节细胞表面表达和胞外域脱落。

• DOI: 10.1074/jbc.m115.684787
• 发表时间: 2016
• 期刊: The Journal of biological chemistry
• 作者: Windheim M