Functions and mechanisms of action of the adenovirus E3 proteins.
In the evolutionary battle between viruses and their hosts, viruses have armed themselves with weapons to defeat the host's attacks on infected cells. Various proteins encoded in the adenovirus (Ad) E3 transcription unit protect cells from killing mediated by cytotoxic T cells and death-inducing cytokines such as tumor necrosis factor (TNF), Fas ligand, and TNF-related apoptosis-inducing ligand (TRAIL). The viral protein E3-gp19 K blocks MHC class-I-restricted antigen presentation, which diminishes killing by cytotoxic T cells. The receptor internalization and degradation (RID) complex (formerly E3-10.4 K/14.5 K) stimulates the clearance from the cell surface and subsequent degradation of the receptors for Fas ligand and TRAIL, thereby preventing the action of these important immune mediators. RID also downmodulates the epidermal growth factor receptor (EGFR), although what role, if any, this function has in immune regulation is uncertain. In addition, RID antagonizes TNF-mediated apoptosis and inflammation through a mechanism that does not primarily involve receptor downregulation. E3-6.7 K functions together with RID in downregulating some TRAIL receptors and may block apoptosis independently of other E3 proteins. Furthermore, E3-14.7 K functions as a general inhibitor of TNF-mediated apoptosis and blocks TRAIL-induced apoptosis. Finally, after expending great effort to maintain cell viability during the early part of the virus replication cycle, Ads lyse the cell to allow efficient virus release and dissemination. To perform this task subgroup C Ads synthesize a protein late in infection named ADP (formerly E3-11.6 K) that is required for efficient virus release. This review focuses on recent experiments aimed at discovering the mechanism of action of these critically important viral proteins.
Lichtenstein
Drew L
DL
Department of Molecular Microbiology and Immunology, Saint Louis University Health Sciences Center, St. Louis, Missouri 63104, USA.
Toth
Karoly
K
Doronin
Konstantin
K
Tollefson
Ann E
AE
Wold
William S M
WS
D000256:Adenoviridae / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology; D000257:Adenoviridae Infections / Q000473:pathology / Q000503:physiopathology / Q000821:virology; D017503:Adenovirus E3 Proteins / Q000235:genetics / Q000502:physiology*; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D004195:Disease Models, Animal; D005822:Genetic Vectors; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D014158:Transcription, Genetic
D017503:Adenovirus E3 Proteins; D015395:Histocompatibility Antigens Class I; C099609:adenovirus death protein, Adenovirus