Tumor necrosis factor (TNF) has a wide range of biological effects in host defense against pathogens. It is capable of inducing cell survival, proliferation and differentiation as well as both apoptotic and necrotic cell death under certain conditions. The TNFR1 receptor belongs to a family of type I transmembrane proteins.

TNFR1, as well as other members of its family, is an elongated molecule composed of an extracellular domain of multiple ~40-residue pseudo repeats, with six cysteines forming three disulfide bridges. These modules are termed CRDs (cysteine-rich domains).

Unlike many receptors, TNFR1 does not have enzymatic activity. Instead, an oligomeric complex, called the death domain (DD) places the intracellular regions of the receptor in proximity for recruitment of signaling proteins with enzymatic activities to amplify the signal transduction and mediate extrinsic signal induced cell death¹.

TNFα, a ligand of TNFR1 binds to the intracellular death domain of TNFR1 and recruits the TNF receptor-associated DD protein (TRADD), which in turn recruits receptor-interacting protein kinase 1 (RIP1), cellular inhibitor of apoptosis proteins 1 and 2 (cIAP1 and 2), and TNF receptor-associated factor 2².

TNFR1-mediated signaling provides potent anti-viral activity, however many viruses have evolved to encode and express molecules that specifically inhibit almost every step of TNFR-induced apoptosis and NF-κB signaling pathways³.