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

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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.