Myxoma T2 protein as a model for poxvirus TNF receptor homologs

Many poxviruses encode a plethora of immunomodulatory proteins, including homologs of cellular cytokine receptors. These receptor mimics, also referred to as viroceptors, are believed to function by binding and sequestering host cytokines thus preventing their signaling cascade prior to receptor engagement. The M-T2 protein of myxoma virus is a TNF receptor homolog that has two distinct activities: the secreted dimeric M-T2 protein binds and inhibits TNFα while the intracellular version permits myxoma virus replication in infected T-lymphocytes by blocking the cellular apoptosis response to the virus infection. Studies with M-T2 mutants reveal that distinct protein domains mediate these two anti-immune properties of this protein.