The myxoma virus tumor necrosis factor (TNF) receptor homolog, M-T2, is expressed both as a secreted glycoprotein that inhibits the cytolytic activity of rabbit TNF-α and as an endoglycosidase H-sensitive intracellular species that prevents myxoma virus-infected CD4+ T lymphocytes from undergoing apoptosis. To compare the domains of M-T2 mediating extracellular TNF inhibition and intracellular apoptosis inhibition, recombinant myxoma viruses expressing nested C-terminal truncations of M-T2 protein were constructed. One mutant, ΔL113, containing intact copies of only two cysteine-rich domains, was not secreted and was incapable of binding rabbit TNF-α yet retained full ability to inhibit virus-induced apoptosis of RL-5 cells. Thus, the minimal domain of intracellular M-T2 protein required to inhibit apoptosis is distinct from that required by the extracellular M-T2 for functional TNF-α binding and inhibition. This is the first report of a virus-encoded immunomodolar protein with two distinct antiimmune properties.
|Number of pages||11|
|Journal||Journal of Virology|
|Publication status||Published - Mar 1997|