EXPRESSION OF THE MYXOMA VIRUS TUMOR-NECROSIS-FACTOR RECEPTOR HOMOLOGAND M11L GENES IS REQUIRED TO PREVENT VIRUS-INDUCED APOPTOSIS IN INFECTED-RABBIT T-LYMPHOCYTES

Myxoma virus is a leporipoxvirus that causes a highly lethal virulent disease known as myxomatosis in the European rabbit. An important aspe ct of myxoma virus pathogenesis is the ability of the virus to product ively infect lymphocytes and spread to secondary sites via lymphatic c hannels. We investigated the infection of the CD4(+) T lymphoma cell l ine RL-5 with myxoma virus and Shope fibroma virus, a related but beni gn leporipoxvirus, and observed that myxoma virus, but not Shope fibro ma virus, was able to productively infect RL-5 cells. We also discover ed that infection of RL-5 cells with Shope fibroma virus or attenuated myxoma virus mutants containing disruptions in either the T2 or the M 11L gene resulted in the rapid induction of DNA fragmentation, followe d by morphological changes and loss in cell integrity characteristic o f cell death by apoptosis. Purified exogenous T2 protein was unable to prevent apoptosis, suggesting that T2 functions intracellularly. Thus , myxoma virus T2, originally described as a secreted homologue of the tumor necrosis factor receptor, and M11L, a novel transmembrane speci es with no known cellular homologue, function to extend virus host ran ge for replication in rabbit T lymphocytes through the inhibition of a poptosis in infected T lymphocytes. (C) 1996 Academic Press, Inc.