Tumor necrosis factor (TNF) is the prototypical member of a large superfamily of structurally related cytokines that are involved in a wide range of activities involved in the regulation of the immune response and developmental processes and that signal mainly through an equally diverse array of receptors included in the TNF receptor superfamily (TNFRSF). TNF has an essential role in the activation of the antiviral immune response, where it acts both directly on virus-infected cells as a cell death-inducing cytokine and indirectly in the activation of the innate and adaptive immune responses against the invading pathogen. Consequently, viruses from different families have devised strategies to evade or modulate these TNF-driven responses. Most strategies involve the expression of virus-encoded intracellular proteins that are able to bind to different proteins of the TNFR signal transduction pathways. Uniquely, poxviruses express secreted TNFR homologues that can bind to soluble TNF, inhibiting its activity by preventing it from binding to the cellular receptors. In the recent years, we have been interested in studying the activity and function of these viral TNFRs (vTNFRs) both in vitro and during infection. We describe recent advances in this field.

Peer reviewed