MC159L protein from the poxvirus molluscum contagiosum virus inhibits NF-kappa B activation and apoptosis induced by PKR

Molluscum contagiosum virus (MCV) is a human poxvirus that causes abnormal proliferation of epithelial cells. MCV encodes specific molecules to contro l host defences, such as MC159L, which as previously shown prevents apoptos is induced by death receptors. However, unlike most poxviruses, MCV lacks a homologue to the E3L and K3L proteins of vaccinia virus, which are involve d in the control of the key antiviral and pro-apoptotic dsRNA-dependent pro tein kinase, PKR. In this study, we analysed the relationship of MC159L to PKR. We found that MC159L is not a direct inhibitor of PKR since it does no t associate with PKR and cannot block PKR-induced phosphorylation of eIF-2 alpha. However, expression of MC159L inhibits apoptosis triggered by PKR th rough death receptor-mediated pathways. In addition, MC159L inhibits NF-kap paB activation induced in response to PKR. Expression of MC159L cannot coun teract the PKR-mediated antiviral action in the context of a poxvirus infec tion, despite its ability to affect these signalling events. These findings show that MC159L is able to interfere with downstream events triggered by PKR in the absence of a direct physical interaction, and assign a role to M C159L in the control of some PKR-mediated biological effects.