Date of Award

Summer 7-25-2018

Degree Type


Degree Name

MS Biology




Daniel B. Nichols, Ph.D.

Committee Member

Allan Blake, Ph.D.

Committee Member

Constantine Bitsaktsis, Ph.D.

Committee Member

Angela Klaus, Ph.D.

Committee Member

Heping Zhou, Ph.D.


Molluscum, MC160, MAVS, Virus


The Molluscum Contagiosum Virus (MCV) causes a common persistent, skin infection. Two MCV immune evasion molecules, MCV MC159 and MC160 contain tandem death effector domains (DEDs). DEDs are found in several host proteins including pro-apoptotic proteins Fas-associated Death Domain (FADD) and procaspase-8 and are well characterized in innate immune signaling. MC159 blocks apoptosis induced by both Tumor Necrosis Factor (TNF) and the Fas ligand (FasL) and inhibits activation the host pro-inflammatory transcription factor nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) (Shisler, 2001; Murao and Shisler 2005). MC160, however, does not inhibit apoptosis, but does dampen TNF-induced NF-κB activation (Shisler, 2001; Nichols and Shisler, 2006). Both MC159 and MC160 inhibit activation of type I interferons induced via the mitochondrial antiviral signaling (MAVS) pathway, an important innate signaling network that senses the presence of a viral double-stranded RNA (dsRNA) and induces an interferon (IFN) response. MC159 interacts with the protein kinases TBK-1 and IKKε. However, the molecular mechanism of MC160 is not well understood. When expressed independently, both the C-terminal domain of MC160 as well as the first DED were reported to inhibit TBK-1 induced IRF-3 activation, whereas the second DED was dispensable (Randall et al., 2013).

The goal of the current project is to identify the molecular mechanism through which MC160 inhibits activation of type I IFNs. We characterized the ability of MC160 constructs to inhibit MAVS- and TBK-1 induced activation of type I IFN. When expressed independently neither MC160 DED1 nor DED2 blocked activation the IFN-β enhancer to the extent of full-length or the MC160 construct that expresses both DEDs. Our current analysis suggests that both DED1 and DED2 are required to fully inhibit activation of type I interferons.

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