Retroviral membrane display of apoptotic effector molecules

Retroviruses have been widely used in gene transmission studies. In this pa per, we show that nonviral apoptotic proteins can be displayed on viral mem brane surfaces and that the displayed proteins can execute their normal eff ector functions. We introduced the genes encoding the apoptosis effector pr oteins, human CD95 ligand (hFasL) or human tumor necrosis factor-related ap optosis-inducing ligand (hTRAIL), into a cell line that packages Moloney mu rine leukemia virus vectors. Retrovirus preparations from these lines kille d target cells efficiently, and target killing was prevented by Fas-lg fusi on protein or soluble TRAIL receptor (sDR5), respectively, We show that the virus preparation exhibiting Fas-specific cytotoxicity has the same densit y as a retrovirus, contains full-length Fast protein, and can be depleted o f infectivity by immunoadsorption with anti-Fast antibody, This novel prope rty of retroviruses-the display of functional effector proteins-may allow t he custom design of reagents whose normal function requires their being emb edded in a membrane.