title: The Molluscum Contagiosum Virus protein MC163 localizes to the mitochondria and dampens mitochondrial mediated apoptotic responses.
abstract: Apoptosis is a powerful host cell defense to prevent viruses from completing replication. Poxviruses have evolved complex means to dampen cellular apoptotic responses. The poxvirus, Molluscum Contagiosum Virus (MCV), encodes numerous host interacting molecules predicted to antagonize immune responses. However, the function of the majority of these MCV products has not been characterized. Here, we show that the MCV MC163 protein localized to the mitochondria via an N-terminal mitochondrial localization sequence and transmembrane domain. Transient expression of the MC163 protein prevented mitochondrial membrane permeabilization (MMP), an event central to cellular apoptotic responses, induced by either Tumor Necrosis Factor alpha (TNF-α) or carbonyl cyanide 3-chlorophenylhydrazone (CCCP). MC163 expression prevented the release of a mitochondrial intermembrane space reporter protein when cells were challenged with TNF-α. Inhibition of MMP was also observed in cell lines stably expressing MC163. MC163 expression may contribute to the persistence of MCV lesions by dampening cellular apoptotic responses.
authors.affiliation: Department of Biological Sciences, Seton Hall University, 400 S. Orange Ave, South Orange, NJ 07079, United States.
authors.forename: Jesse
authors.initials: J
authors.lastname: Coutu
authors.affiliation: Department of Microbiology, University of Illinois, 601 S. Goodwin Ave., Champaign-Urbana, IL 61801, United States.
authors.forename: Melissa R
authors.initials: MR
authors.lastname: Ryerson
authors.affiliation: Institut für Mikrobiologie der Bundeswehr, Neuherbergstrasse, 1180937 München, Germany.
authors.forename: Joachim
authors.initials: J
authors.lastname: Bugert
authors.affiliation: Department of Biological Sciences, Seton Hall University, 400 S. Orange Ave, South Orange, NJ 07079, United States. Electronic address: daniel.nichols@shu.edu.
authors.forename: Daniel
authors.initials: D
authors.lastname: Brian Nichols
mesh_terms: D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D002463:Cell Membrane Permeability / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D006835:Hydrazones / Q000494:pharmacology; D008928:Mitochondria / Q000378:metabolism*; D051336:Mitochondrial Membranes / Q000378:metabolism*; D008976:Molluscum Contagiosum / Q000821:virology; D008977:Molluscum contagiosum virus / Q000378:metabolism*; D000071137:Poly (ADP-Ribose) Polymerase-1 / Q000378:metabolism; D019311:Staurosporine / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014764:Viral Proteins / Q000378:metabolism*
chemical_list: D006835:Hydrazones; C000619337:MC163 protein, Molluscum Contagiosum virus; D014409:Tumor Necrosis Factor-alpha; D014764:Viral Proteins; C070053:carbonyl 3-chlorophenylhydrazone; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D053148:Caspase 3; D019311:Staurosporine
keywords: Apoptosis; MC163; Mitochondrial membrane permeabilization; Molluscum Contagiosum Virus; TNF-α