J Biol Chem 2006 May 22; (Read article online)

Tomai E, Butz K, Lohrey C, von Weizsäcker F, Zentgraf H, Hoppe-Seyler F

Peptide aptamers (PAs) can be employed to block the intracellular function of target proteins. Little is known about the mechanism of PA-mediated protein inhibition. Here, we generated PAs which specifically bound to the duck hepatitis B virus (DHBV) core protein. Among them, PA34 strongly blocked DHBV replication by inhibiting viral capsid formation. We found that PA34 led to a dramatic intracellular redistribution of its target protein into perinuclear inclusion bodies, which exhibit the typical characteristics of aggresomes. As a result, the core protein is efficiently removed from the viral life cycle. Corresponding findings were obtained for bioactive PAs which bind to the hepatitis B virus (HBV) core protein or to the human papillomavirus-16 (HPV16) E6 protein, respectively. The observation that PAs induce the specific sequestration of bound proteins into aggresomes defines a novel mechanism as to how this new class of intracellular inhibitors blocks the function of their target proteins.