Myxoma virus expresses a TNF receptor homolog with two distinct functions

Myxoma virus, a member of the poxvirus family of DNA viruses, encodes many virulence factors to combat and evade the host immune responses. Among the virus-encoded immune-modulators is M-T2, a tumor necrosis factor receptor (TNF-R) homologue. M-T2 is secreted as monomeric and dimeric species that bind and inhibit rabbit TNF in a species-specific manner. Deletion analysis indicates that the anti-TNF function is mediated by the first three of four cysteine rich domains (CRDs) of M-T2. In addition, the intracellular form of M-T2 has the ability to block virus-induced apoptosis in lymphocytes, and the first two CRDs appear to be sufficient for this function. Although the mechanisms for the anti-TNF and anti-apoptotic functions of M-T2 are not yet fully defined, we postulate that these dual activities of M-T2 are mediated through different functional motifs and abrogate distinct cellular responses to virus infection.