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

人类腺病毒引起呼吸道、胃肠道和眼睛的急性和持续性感染。另一方面，腺病毒也被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引起持续感染和分化疾病。通过研究腺病毒E3蛋白与免疫重要宿主分子之间的分子相互作用，我们先前证明了E3蛋白表现出多种促进免疫逃避的免疫调节功能。到目前为止，51种人类ad中只有两种ad（均来自C亚群）的E3蛋白被功能表征。我们之前的研究以及下面的新数据表明，E3/ 49k是第一个分泌的E3蛋白，并提出了一种新的、根本不同的免疫调节E3活性，这种活性不像预期的那样直接作用于感染细胞，而是作用于未感染的淋巴细胞。我们的主要目的是表征E3/49K的功能并鉴定其细胞靶分子。

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.