Adenovirus E3 Proteins: 14.7K, RID, and gp19K Inhibit Immune-Induced Cell Death; Adenovirus Death Protein Promotes Cell Death

Abstract

The adenovirus E3 transcription unit encodes proteins named E3-14.7K, RID, and E3-gp19K that prevent killing of infected cells by the host immune system. Tumor necrosis factor (TNF), a cytokine secreted by activated monocytes and cytotoxic T lymphocytes (CTL), can induce apoptosis when it engages the TNF receptor on target cells. E3-14.7K and RID independently prevent TNF-induced apoptosis. Fas ligand, which is expressed on activated CTL and natural killer cells, induces apoptosis when it engages its receptor, Fas, on target cells. RID blocks apoptosis through Fas by stimulating the clearance of Fas from the infected cell surface and its degradation in lysosomes. CTL induce apoptosis when the T cell receptor engages the MHC class I antigen–peptide complex on target cells. E3-gp19K inhibits killing by CTL by blocking transport of MHC class I antigens to the infected cell surface. After virus replication is complete, the cell lyses and releases virus particles; this cell lysis is mediated by the E3-coded adenovirus death protein.