Molluscum contagiosum virus inhibitors of apoptosis: The MC159 v-FLIPprotein blocks Fas-induced activation of procaspases and degradation ofthe related MC160 protein

摘要

Molluscum contagiosum virus contains two open reading frames, MC159 and MC160, that encode proteins with death effector domains resembling those of cellular regulators of apoptosis. Previous transfection analyses indicated that the MC159 protein binds to cellular FADD and inhibits Pas-induced cytolysis. For further studies, we inserted the MC159 or MC160 gene into the genome of vaccinia virus that had its own major anti-apoptosis gene deleted. The MC159-expressing virus blocked Pas-induced activation of caspase-3 and -8, degradation of PARP, and cleavage of DNA, whereas the parental vaccinia Virus did not. The MC159 protein bound to procaspase-8, in addition to FADD, and was included in a complex with Fas upon receptor activation. Although the MC160 protein associated with FADD and procaspase-8 in co-immunoprecipitation studies, no protection against morphological or biochemical changes associated with Pas-induced apoptosis were discerned and the MC160 protein it self was degraded. Go-expression of MC159, as well as other caspase inhibitors, protected the MC160 protein from degradation, suggesting a functional relationship between the two viral proteins.