Date of Award
PhD Molecular Bioscience
Daniel Brian Nichols, Ph.D.
Constantine Bitsaktsis, Ph.D.
Jessica Cottrell, Ph.D.
Angela V. Klaus, Ph.D.
John Siekierka, Ph.D.
IKK, MC163, MCV, Molluscum Contagiosum Virus, NF-κB, TNF𝛼
Poxviruses utilize numerous strategies to prevent activation of the host pro-inflammatory transcription factor, NF-κB. For example, the Molluscum Contagiosum Virus (MCV) expresses several immune evasion molecules that either work directly at the level of NF-κB or IKK, the upstream kinase complex required for canonical NF-κB activation. Presumably these strategies allow MCV to evade host innate immune responses and cause persistent infections. In this dissertation I report the identification of a novel MCV inhibitor of NF-κB activation. Ectopic expression of the MC163 protein in HEK 293T cells resulted in a significant decrease in TNFα- induced NF-κB activation as measured by the dual luciferase reporter assay. In contrast, MC163 expression had no detectable effect on MAVS-induced activation of the IFNβ-promoter. In addition, MC163 expression dampened IKKα- and IKKb mediated NF-κB activation suggesting that MC163 may target the IKK complex. Not surprisingly, immunoprecipitation experiments detected interactions between MC163 and IKKα. My data reveals an additional function of MC163 as an NF-kB antagonist and may represent an additional strategy used by MCV to subvert host immune responses.
De Martini, William, "Characterization of Immune Evasion Properties of the Molluscum Contagiosum Virus MC163 Protein" (2019). Seton Hall University Dissertations and Theses (ETDs). 2704.
Available for download on Monday, October 14, 2024