Selective Expression of Nonsecreted Interferon by an Adenoviral Vector Confers Antiproliferative and Antiviral Properties and Causes Reduction of Tumor Growth in Nude Mice

Replication-deficient adenoviruses expressing human interferon-α2b (HuIFN-α2b) or the hybrid IFN-α2α1 or those with the secretory signal deleted, whose express is driven by the α-fetoprotein (AFP) promoter, were constructed and characterized. Synthesis of IFN protein and secretion or intracellular retention were tested by Western blotting and immunoassay. Expression of IFN by the recombinant adenoviruses was restricted to cells that constitutively express AFP. In these cells, expression of both secreted and nonsecreted recombinant IFN resulted in inhibition of cell proliferation, resistance to viral infection, induction of major histocompatibility complex (MHC) class I expression, increased apoptosis, and activation of an IFN-stimulated response element (ISRE)-containing promoter. Also, the induction of protein kinase R (PKR), increased phosphorylation of Stat1, and accumulation of hypophosphorylated pRb were observed for both the secreted and nonsecreted IFN, suggesting that the nonsecreted IFN may act t...