Expression of the myxoma virus tumor necrosis factor receptor homologue and 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 aspect of myxoma virus pathogenesis is the ability of the virus to productively infect lymphocytes and spread to secondary sites via lymphatic channels. We investigated the infection of the CD4+ T lymphoma cell line RL-5 with myxoma virus and Shope fibroma virus, a related but benign leporipoxvirus, and observed that myxoma virus, but not Shope fibroma virus, was able to productively infect RL-5 cells. We also discovered that infection of RL-5 cells with Shope fibroma virus or attenuated myxoma virus mutants containing disruptions in either the T2 or the M11L gene resulted in the rapid induction of DNA fragmentation, followed by morphological changes and loss in cell integrity characteristic of 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 species with no known cellular homologue, function to extend virus host range for replication in rabbit T lymphocytes through the inhibition of apoptosis in infected T lymphocytes.
Macen
J L
JL
Department of Biochemistry, University of Alberta, Edmonton, Alberta, T6G 2H7, Canada.
Graham
K A
KA
Lee
S F
SF
Schreiber
M
M
Boshkov
L K
LK
McFadden
G
G
D000818:Animals; D017209:Apoptosis; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism / Q000821:virology*; D004249:DNA Damage; D012776:Fibroma Virus, Rabbit / Q000235:genetics / Q000502:physiology; D015870:Gene Expression; D009233:Myxoma virus / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*; D011817:Rabbits; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000502:physiology*; D015843:Serpins / Q000235:genetics / Q000502:physiology; D014407:Tumor Cells, Cultured; D014764:Viral Proteins / Q000235:genetics / Q000502:physiology*
D018124:Receptors, Tumor Necrosis Factor; D015843:Serpins; D014764:Viral Proteins; C077309:M11L protein, Myxoma virus