David H. Kirn, Editor tumor cell can cause cell destruction by several mechanisms (Table 1). First, viral proteins, including the E3 11.6 adenovirus death protein (16) and E4ORF4 (17), that are expressed late in the course of infection are directly cytotoxic. Deletion of the corresponding genes significantly delays death of infected cells. In addition, expression of E1A early during the adenovirus lifecycle sensitizes cells to tumor necrosis factor (TNF)-mediated killing (18). This effect is inhibited by the E3 proteins 10.4/14.5 and 14.7; deletion of these E3 proteins leads to an increase in TNF expression in vivo and enhanced cell sensitivity to TNF. Finally, viral replication in and lysis of tumor cells induces cell-mediated immunity to tumor cells in model systems (R. Martuza, this series). Whether patients will benefit from a similar effect remains to be determined.