Inhibition of Tumor Necrosis Factor (TNF) Signal Transduction by the Adenovirus Group C RID Complex Involves Downregulation of Surface Levels of TNF Receptor 1

Abstract

Adenoviruses employ multiple genes to inhibit the host antiviral responses. There is increasing evidence that these immunoregulatory genes may function either during lytic or latent infection. Adenovirus early transcription region 3 (E3) encodes at least seven proteins, five of which block the acquired or innate immune response. Previous findings from this laboratory demonstrated that the E3 proteins 10.4K and 14.5K, which form a complex in the plasma membrane, inhibit tumor necrosis factor (TNF)-induced activation of NF-κB and the synthesis of chemokines. To determine the mechanism of inhibition of these pathways by the adenovirus E3 10.4K/14.5K proteins, we have examined the effects of this viral complex on the inhibition of AP-1 and NF-κB activation by TNF and found a reduction in assembly of the TNF receptor 1 (TNFR1) signaling complex at the plasma membrane accompanied by downregulation of surface levels of TNFR1.