THE ADENOVIRUS E3-10.4K 14.5K COMPLEX MEDIATES LOSS OF CELL-SURFACE FAS (CD95) AND RESISTANCE TO FAS-INDUCED APOPTOSIS/

Cytotoxic T cells use Fas (CD95), a member of the tumor necrosis facto r (TNF) receptor superfamily, to eliminate virus-infected cells by act ivation of the apoptotic pathway for cell death, The adenovirus E3 reg ion encodes several proteins that modify immune defenses, including TN F-dependent cell death, which may allow this virus to establish a pers istent infection, Here we show that, as an early event during infectio n, the adenovirus E3-10.4K/14.5K complex selectively induces loss of F as surface expression and blocks Fas-induced apoptosis of virus-infect ed cells, Loss of surface Fas occurs within the first 4 h postinfectio n and is not due to decreased production of Fas protein. The decrease in surface Fas is distinct from the 10.4K/14.5K-mediated loss of the e pidermal growth factor receptor on the same cells, because intracellul ar stores of Fas are not affected, Further, 10.4K/14.5K, which was pre viously shown to protect against TNF cytolysis, does not induce a loss of TNF receptor, indicating that this complex mediates more than one function to block host defense mechanisms, These results suggest yet a nother mechanism by which adenovirus modulates host cytotoxic response s that may contribute to persistent infection by human adenoviruses.